Effects of Tiny Moss Bryum capillare meal on Growth Parameter, Haematology, Histology and Carcass Quality of Clarias gariepinus (Burchell) Juveniles- Juniper Publishers

 

Oceanography & Fisheries Open Access Journal - Juniper Publishers

Abstract

This research determines the effects of Tiny Moss Bryum capillare meal, on growth parameter, Haematology, Histology and Carcass Quality of Clarias gariepinus (Burchell) Juveniles. The study was conducted for Fifty-Six (56), under a completely randomized design day. The final body weight and the daily weight gain increase as the Tiny Moss (Bryum capillare) inclusion increased among the individual treatment. The results of the feed conversion ratio were significantly (p <0.05) different among the groups, such that T1 and T2 had the best FCR followed by T5 and T6 which had similar values but the T4 had the least value. The amino acid profile showed that the Glutamic Acid, Aspartic Acid, Valine, Threonine, Serine, Phenylalanine, Proline and Methionine increased in value while Lysine, Leucine, Arginine, Alanine, Isoleucine, Glycine, Histidine and Tryptophan reduced in value and there was no significant change in cysteine (%) all were significantly at (P<0.05). The haematological parameters of the catfish (Clarias gariepinus) juveniles fed graded levels of diets containing Tiny Moss (Bryum capillare) were not significantly different (P>0.05). The histological analysis of tiny Moss (Bryum capillare) feed shows normal skin architecture with well outlined epithelia cell (EC) moderate effect on the skin layer with moderate necrosis (N) of the muscular region with the epithelia lining and superficial spreading of melanoma (M) restricted to the epidermis The heart shows normal cardiac tissue with cardiac cell (CC), cardiac fiber (CF) cardiac muscles (CM) shows moderate aggregate of myocardiac inflammation (AMI). The gill showed section of gill with ghost (G) appearance with severe aggregate of inflammatory cell (AIC). The liver cells revealed severe effect on the hepatic tissue with severe intra hepatic inflammation (IHI) and intra hepatic hemorrhage (IHIH). The damage done to these organs as the result of the feeds correlates with the concentrations of the feeds in each experimental tank.

Keywords: Tiny Moss meal (Bryum capillare); Haematology; Histology; Carcass Quality; Clarias gariepinus

Abbreviations: EC: Epithelia Cell; N: Necrosis; M: Melanoma; CC: Cardiac Cell; CF: Cardiac Fiber; CM: Cardiac Muscles; AMI: Myocardiac Inflammation; G: ghost; AIC: Aggregate of Inflammatory Cell; IHI: Intra Hepatic Inflammation; IHIH: Intra Hepatic Hemorrhage; EDTA: Ethyl Diamine Tetracetic Acid; AAS: Atomic Absorption Spectrophotometer; PAS: Periodic Acid Schiff’s Reagent; H&E: Haematoxyllin-Eosin; CP: Crude Protein; CL: Crude Lipid; CF: Crude Fiber; M: Moisture; NFE: Nitrogen Free Extract; Do: Dissolved Oxygen; TDS: Total Dissolved Solid; NCFRs: Non-conventional feed resources; RDA: Recommended Dietary Allowance; EAAs: Essential or Indispensable Amino Acids

Introduction

Mosses belong to the simplest land/water plants. At the same time, they belong to the second largest taxonomic group in the plant kingdom: bryophytes Asakawa [1]. There are around 25,000 bryophyte species, which can be found in most ecosystems worldwide and include mosses (Musci ~ 8000 species), liverworts (Hepaticae ~ 6000 species) and hornworts (Anthocerotae ~ 1000 species) Klavina [2]. The major structural components of mosses are carbohydrates [2,3], and they also contain secondary metabolites with possibly high biological activity Asakawa [1]. B. capillare is a very common moss that grows in tufts or patches, with stems mostly 1-3 cm tall. Dry plants usually have corkscrew-like shoots, with leaves spirally twisted around the stem. However, in some populations the dry shoots have leaves that are straight or only slightly twisted. The broad leaves are 2-5 mm long, and widest at or above the halfway point. The margins are narrowly recurved and have a well-defined border of narrow cells. The nerve extends into a fine, pale green hair point, which can be short or quite long. B. capillare is dioicous. The large (3.5-5 mm long), cylindrical, drooping capsules ripen in spring and summer, and are borne on a reddish seta up to 3 cm tall.

The use of plants by people has a history as old as the existence of humanity. From ancient times to the present, humanity has sought solutions to diseases by making use of plants in nature. Tiny Moss (Bryum capillare) have been used in many areas since ancient times, thanks to their different properties. They antimicrobial activities against bacteria and their use in the treatment of various diseases, such as acne, hemorrhoids, and skin diseases, the active substance called Sphagnol, which is found in the Sphagnum genus moss, is used [4]. Non-antimicrobial activities of mosses are classified according to their different properties in various fields such as horticulture and agriculture, animal husbandry, fuel, food, construction industry, cosmetics industry, household, clothing making, and ecological uses of moss [5]. The nutritional value of Tiny Moss (Bryum capillare) is well recognized, having relatively high protein, amino acid and fatty acid contents and high fiber, and so Tiny Moss (Bryum capillare) can be used as dietary supplements for fish and other animals. Specifically, lysine and methionine contents are higher in Tiny Moss compared to other plants and, therefore, more suitable as ingredients for animal feed [6]. To date, the composition of mosses has not been much studied from the perspective of their application potential, but mainly has been concentrated on the investigation of specific substance groups, such as fatty acids, lipids, essential oils [7,8]. Another reason to study the composition of bryophytes is related to the need to understand their metabolism.

The most commonly practiced feed supplementation is the dispensation of ground feedstuff such as cereals bran and domestic left-over/kitchen waste to feed fish. Though these are known to enhance growth they may not be complete or balanced. Fishes fed on incomplete feeds will suffer deficiency diseases or symptoms attributable to lack of ingredients. Fagbenro et al. [9] observed that balanced/complete diets are formulated by combination of different essential nutrients in different proportions (Protein, Carbohydrate, lipids, Vitamins. Minerals). The increased use of alternate sources of plant products for fishmeal in fish feeds, information on mineral requirements and bioavailability of essential nutrients is necessary to improve performance and health of fish, to minimize the discharge of excessive nutrients excreted into natural waters, and to prevent mineral deficiencies in farmed fish. Further research on a better estimate of feedstuff’s amino acid bioavailability, as well as maintenance requirement and protein accretion of fish, will result in more efficient use of alternate protein sources of protein in fish feeds and lower nitrogenous waste from commercial aquaculture. A significant achievement has been on the effective use of alternate lipids particularly vegetable oils, animal fats DHA-rich marine microalgae and omega-3 long-chain PUFA canola oil to replace fish oil in fish feeds and sustain optimum growth, feed utilization and product quality. However, questions related to the possibility of achieving an optimal balance between different PUFA in terms of the ratio of n-3/n-6 fatty acids and EPA/DHA for optimal health as well as the successful reproductive performance of fish and proper levels of PUFA (particularly EPA/DHA and EPA/ARA ratio) needed for better survival of larval marine fish, must be addressed.

Catfish culture has overtime become the desire of most fish farmers due to its continuous increasing demand [10]. As the world’s campaign for the consumption of less fatty food continues to intensify, people consider fish and its products as a reliable and affordable option for required protein [11,12]. Food is a major requirement for all living organisms including fish for growth, reproduction and body maintenance (WHO 2021). In fish culture systems, the importance of feed cannot be over emphasized, since feed is the most expensive input in terms of cost in fish production. Nutritional requirement of fish is necessary in order to formulate an economical and nutritionally balanced diet for the fish (Solomon et al. 2012). To sustain fish under culture, supplementary diet must be provided to complement natural feeds supply (Karapan and Agbottidis, 2002). Feed stuffs used in aquaculture to provide basic nutrients such as protein, carbohydrate, minerals, water, vitamins and lipids are expensive because of their competitive uses by man and other animals (Dunham et al., 2001). Mosses have been neglected as a study subject for a long time. Recent research shows that mosses contain remarkable and unique substances with high biological activity. Several studies have investigated the use of Tiny Moss (Bryum capillare) as an ingredient in feeds for carp species, such as L. minor [13] or L. minuta in feeds for common carp Cyprinus carpio. Furthermore, L. minor has been supplemented in diets of rohulabeorohita [6], grass carp Ctenopharyng odonidella and silver carp Hypophthalmichthys molitrix [14], but there is paucity of information on the use of Tiny Moss (Bryum capillare) as an ingredient in feeds for Catfish Clarias gariepinus. The aim of the study is to determine the effects of Tiny Moss meal Bryum capillare on Growth Parameter, Haematology, Histology and Carcass Quality of Clarias gariepinus (Burchell) Juveniles that is lacking.

Materials and Methods

Experimental Site

The research was conducted in the Fisheries Research Unit of Ebonyi State University, Abakaliki, in the Department of Fisheries and Aquaculture Research and Teaching Farm. The area is located in the South East of Nigeria and has a prevailing tropical climate with mean annual rainfall of about 1500mm. The average ranges of ambient temperature of 24oC to 38oC with a yearly average of 34oC. The average relative humidity ranges from 60 to 94 percent with a year average of about 83 percent. Abakaliki lies between latitude 50 and 60 N and between longitudes 70 and 80 E at an elevation of 59m above sea level within the South Eastern Agricultural Zone of Nigeria (GPS, 2018).

Experimental fish

One hundred and eighty (180) catfish (Clarias gariepenus) juveniles with average initial body weight of Mean ± SD (g) and STD Length Mean ± SD (cm) was obtained from Amazons Farms hatcheries, Ugwuachara and was divided into six treatments. Each treatment contained 30 fish. Each of the treatment group was further subdivided into three replicates of 10 fish per replicate. All the fish for the study was homogenous in body weights and apparently healthy and was acclimated to farm conditions for 1 week prior to the commencement of the experiment.

Collection and Preparation of Bryum capillare

Bryum capillare was harvested in Amaogwugwu Ndukwein Amasiri, Afikpo North Local Government Area of Ebonyi state. Fresh Bryum capillare was harvested from pond within Amaogwugwu Ndukwe in Amasiri, Afikpo North Local Government Area of Ebonyi state with the help of hand net, scoop net as well as sieve and then transported in bags to the house where it was dried under room temperature. This was grinded using hammer grinding machine into powdered form and used whenever required for fish feed preparation.

Preparation of Experimental Diets

The dietary ingredients for the experiment include Bryum capillare meal. Other ingredients that will contain in the feed are fishmeal, soybean meal, maize, vitamin Premix, mineral premix, salt and vitamin E (antioxidant). Six different diets was compounded for experiment one each containing varying levels of the experimental diet except the control. The gross composition of the experimental diets is shown in Table 1. All the diets contain the different proportion of test ingredients. The diets was all isonitrogenous (40%CP). In preparing the diet the two protein sources was included in the ratio of 2:1. Dry ingredients was ground to a powdery form to aid assimilation by fish using a gasolin driven grinding machine in Abakaliki. The diets was thoroughly mixed with each experimental diet, Vitamin E antioxidant was added to the feed at 400ppm i.e. 400mg/kg. The dough was pelleted using a locally fabricated pelleting machine with a 2.0mm die. Diets was immediately sun dried and later broken mechanically into small sizes.

Fish Premix (vital fish) manufactured by Animal Care Service Consult (Nig) Ltd. Lagos, Supplied the following per kg of premix: Vitamin A, 5000,00 IU; Vitamin D3 800,000 IU; Vitamin E, 12,000 mg; Vitamin K, 1,5000 mg; Vitamin B1, 1,000 mg; Vitamin B2, 2,000 mg, Vitamin B6, 1,500 mg; Niacin,12,000 mg; pantothenic acid, 20.00 mg; Biotin,10.00 mg; Vitamin B12, 300.00 mg; folic acid, 150,000 mg; choline, 60,000 mg; manganese, 10,000mg; iron;15,000 mg, zinc 800.00 mg; Copper 400.00 mg; Iodine 80.00 mg; cobalt 40 mg; selenium 8,00 mg. BBRCM= Bovine blood-rumen content mixture.

Diet Performance Evaluation

Growth performance and nutrient utilization of fish was determined following the methods of Jimoh, and Aroyehun, (2011) in term of Final Individual Weight, Survival (%), Specific Growth Rate (SGR %/ day), Feed Conversion Ratio, (FCR) and Protein Efficiency Ratio (PER), Net Protein Utilisation (NPU) responses was calculated as

Haematological Analysis

Blood (1-2ml) was collected from the vertebral caudal blood vessel according to Schmit et al., (1999), using disposable 2ml syringe and needle. The blood was emptied into the heparinized blood bottle treated with Ethyl Diamine Tetracetic Acid (EDTA). A blood sample was centrifuge (1500 rpm for 7mins) to obtain the blood plasma. Plasma samples was stored at (-200C) for the electrochemical and biochemical analysis. Computerized method employing System KX-2INTM Automated Hematology Analyzer was used in blood analysis, the KX-2IN is an ideal hematology analyzer for a clinical satellite laboratory or research testing. Spectrophotometric method was used for biochemical analysis as described by Svobodova et al. [15]. While the plasma electrolytes was determined using corning 400 flame photometer. Other metals were determined using (a back) Model 200A flame of the Atomic Absorption Spectrophotometer (AAS).

Histological Examination of Test Organ

At the end of the experiment, one fish per treatment, that is, three fish per concentration were sampled after 96hours of exposure for histological analysis, the test organism was killed with a blow on the head, using a mallet and was dissected to remove the vital organs (gill, liver, kidney and skin). The organs were fixed in 10% formalin for three days after which the tissue was dehydrated in periodic acid Schiff’s reagent (PAS) following the method of Hughes & Perry, [16], in graded levels of 50%, 70%, 90% and 100% alcohol for 3 days, to allow paraffin wax to penetrate the tissue during embedding. The organs were embedded in malted wax. The tissue was sectioned into thin sections (5-7µm), by means of a rotatory microtome and was dehydrated and stained with Harris haematoxyllin-eosin (H&E) stain, Bancroft & Cook [17], using a microtone and each section were cleared by placing in warm water (38oC), where it was picked with clean slide and oven-dried at 58oC for 30 minutes to melt the wax. The slide containing sectioned materials/tissue were cleared using xylene and graded levels of 50%, 70%, 90%, 95% and 100% alcohol for two minutes each.

The section was stained in haematoxyline eosin for ten minutes. The stained slide was observed under a light microscope at varying X100 magnification, sections were examined and photographed using an Olympus BH2 microscope fitted with photographic attachment (Olympus C35 AD4), a camera (Olympus C40 AB-4) and an automatic light exposure unit (Olympus PM CS5P).

Biochemical Composition (Proximate) Analysis

The biochemical composition of the carcass of the experimental fish was run to determine the Crude Protein (CP), crude Lipid (CL), Crude Fiber (CF), Moisture (M), Ash and Nitrogen Free Extract (NFE), using standard methods [18]. Nitrogen was determined by the micro-kjedahl method (Pearson, 1976) and the crude protein was taken as N% x 6.25 (constant factor) where N is equal to Nitrogen content per 100g sample. Total carbohydrate was determined using the phenol-sulphuric acid method. The crude fibre was obtained by dry ashing of the sample at 550oC dissolved in 10% HCl (25ml) and 5% Lanthanum Chloride (2ml) boiled, filtered and made up to standard volume with distilled water.

Water quality Analysis

The water quality parameters were recorded for temperature, dissolved oxygen (Do) content, pH and conductivity before and after the experiment. pH was determined using a digital pH meter (Mettler Toledo 320). DO and conductivity were measured using a digital dissolved oxygen meter (oxygen analyzer model JPB-607 portable) once in a day at 8.00am. The water quality was determined using the method of America Public Health Association (APHA, 2000) Model Number, E-9909 (pH, TDS, Salinity, EC, Temp.)

Method of Statistical Analysis

The data was collated and analysed using descriptive statistics, one way analysis of variance and Pearson’s correlation. The differences in the means between both values was assessed with Duncan multiple range test Using SPSS version 21 at P<0.05 significant level.

Results

The result of final total length of the Clarias gariepinus fed diets containing Tiny Moss (Bryum capillare) presented in Table 2, showed that there were significant (p<0.05) differences in the final total length during the period of the study. Though, the highest final total length was recorded among the T5, T3 and T1 respectively followed by T6 while T4 and T3 had similar records which were the least among the groups.

Proximate analysis of the Tiny Moss (Bryum capillare) in the diets

The result of the proximate composition of the diets containing Tiny Moss (Bryum capillare) used for feeding the Clarias gariepinus in the experiment is presented in table 3.

The result of proximate analysis of the fish diet containing Tiny Moss (Bryum capillare) in the diets as presented in the Table 3 showed varying levels of nutrients in diets containing Tiny Moss (Bryum capillare) for the experiment. The T6 diet had the highest percentage level of crude protein followed by T4 then T5 and T1, while T3 and T2 had the least crude protein. The crude fat was also highest in T6 followed by T4, T5, T1, T3 and T2 respectively. The crude fibre showed close similarities in the values such that they followed this trend; T2, T3, T1, T5, T4 and T6 respectively. The ash content, Moisture content Nitrogen Free Extract and Dry matter content equally showed little variations among the individual groups Performance of Clarias gariepinus Fed diets containing Tiny Moss (Bryum capillare).

The result of the productive performance of the Clarias gariepinus fed the diets containing Tiny Moss (Bryum capillare) used for feeding the fish in the experiment is shown in table 4.

Means with the same superscripts in the same column are not significantly different at P>0.05, while those with different superscripts in the same column are significantly different at same level.

%NFE =100 – (%CP+%CFAT+%CFIBRE+%ASH+%M); %DM = 100 - %M

Means with the same superscripts in the same column are not significantly different at P>0.05, while those with different superscripts in the same column are significantly different at same level.

The Total Dissolved Solid (TDS) of the pond containing graded levels of Tiny Moss (Bryum capillare) meal showed close relationship in body weights of the fish varying levels of Tiny Moss (Bryum capillare) at the start of the experiment. The Total Dissolved Solid (TDS) significantly increase (P<0.05) at T4 as the Tiny Moss (Bryum capillare) inclusion increased up to 4% among the individual treatment, followed by T1, T3, T5 and T6 that had similar values whereas T2 had the least Total Dissolved Solid (TDS) which the mean differences were statistically significant (p<0.05) among the individual treatments.

The productive performance of the Clarias gariepinus Fed diets containing Tiny Moss (Bryum capillare) as indicated in the Table 4, showed close relationship in body weights of the fish varying levels of Tiny Moss (Bryum capillare) at the start of the experiment. The final body weight and the daily weight gain decreased as the Tiny Moss (Bryum capillare) inclusion increased among the individual treatment, such that the T1 had highest final body weight and daily weight gain among those in control group (T1) followed by T2 then T3, but T5 and T6 had similar values whereas T4 had the least weight gain, which the mean differences were statistically significant (p<0.05) among the individual treatments. There were no significant (p>0.05) differences in the daily feed intake and the total feed intake during the period of the study. Though, the highest feed intake was recorded among the T3 while others had similar records of feed intake among the groups. The results of the feed conversion ratio were significantly (p <0.05) different among the groups, such that T1 and T2 had the best FCR followed by T5 and T6 which had similar values but the T4 had the least value. There were significant (p<0.05) differences in the survival rate during the period of the study such that T2 recorded the highest survival rate, followed by T3 and T6 while T4 and T5 had similar records and the least survival rate among the groups. Water Quality of the pond containing Clarias gariepinus fed diet with Tiny Moss (Bryum capillare). The result of the water quality of the pond containing clarias gariepinus fed diet with Tiny Moss (Bryum capillare) in the experiment is presented in table 5.

Means with the same superscripts in the same column are not significantly different at P>0.05, while those with different superscripts in the same column are significantly different at same level.

The result of the average water quality of the pond containing Clarias gariepinus fed diet with Tiny Moss (B capillare) in the experiment as presented in table 5, indicated that there were similarities in the pH level of the water such that the T3, T4, T5 and T6 had the same marginally higher pH followed by T2 whereas T1 had the least pH, which the mean differences were statistically not significant (p>0.05) among the individual treatments. The Total Dissolved Solid (TDS) of the pond containing graded levels of Tiny Moss (Bryum capillare) meal as indicated in the Table 5, showed close relationship in body weights of the fish varying levels of Tiny Moss (B capillare) at the start of the experiment. The Total Dissolved Solid (TDS) significantly increase (P<0.05) at T4 as the Tiny Moss (B capillare) inclusion increased up to 4% among the individual treatment, followed by T1, T3, T5 and T6 that had similar values whereas T2 had the least Total Dissolved Solid (TDS) which the mean differences were statistically significant (p<0.05) among the individual treatments.

The result of the water conductivity of the pond containing Clarias gariepinus fed diet with Tiny Moss (B capillare) in the experiment as presented in table 5, indicated that their significant differences (P<0.05) among the group such that T4 (4% inclusion of Tiny Moss (B capillare) meal) had the highest level of water conductivity followed by T1, T3 T5 and T6 that had similar conductivity while T2 (2% inclusion of Tiny Moss (B capillare) meal) had the least. The average water salinity of the pond containing graded levels of Tiny Moss (B capillare) meal as presented in the Table 5 were similar in their individual salinity of the water at varying levels of Tiny Moss (B capillare) during experiment. The average salinity is not significantly different (P>0.05) among the individual group as the Tiny Moss (B capillare) inclusion increased. Though there were marginal increases such that T4, had increased salinity followed by T2, then T3 and T6 whereas T5 had the least value which the mean differences were statistically not significant (p>0.05) among the groups.

The result of the average ammonia content of the water in the pond containing Clarias gariepinus fed diet with Tiny Moss (B capillare) meal in the experiment as presented in table 5. This indicated that there were significant differences (P<0.05) in the ammonia content of the water such that the T4, had the highest ammonia concentration followed by T3, T5 and T6 which had the same ammonia concentration, while T1 and T2 had ammonia concentration. The average Temperature (OoC), Nitrite (NO3), Nitrate (NO2), and Dissolved oxygen (DO) of the pond containing graded levels of Tiny Moss (Bryum capillare) meal as presented in the Table 5 were similar in their individual water at varying levels of Tiny Moss (Bryum capillare) inclusion during experiment their results indicated no significant differences among the groups.

Haematological parameters of Catfish Juveniles fed Tiny Moss (Bryum capillare) meal. The result of the average haematological parameters of catfish (Clarias gariepinus) juveniles fed diets containing Tiny Moss (Bryum capillare) is presented in table 6. The result of average haematological parameters of catfish (Clarias gariepinus) juveniles fed diet containing Tiny Moss (Bryum capillare) is presented in the Table 6. The study showed that the haematological parameters of the catfish (Clarias gariepinus) juveniles fed graded levels of diets containing Tiny Moss (Bryum capillare) were not significantly different (P>0.05). Though there were marginal variations among the individual group, there were still a lot of similarities among the values in each of the groups. Biochemical Characteristics of Catfish Juveniles fed Tiny Moss (Bryum capillare) meal. The result of the average biochemical characteristics of Catfish (Clarias gariepinus) juveniles fed diets containing Tiny Moss (Bryum capillare) is presented in table 7.

Means with the same superscripts in the same column are not significantly different at P>0.05, while those with different superscripts in the same column are significantly different at same level.

The result of average biochemical characteristics of catfish Clarias gariepinus juveniles fed diet containing Tiny Moss (Bryum capillare) is presented in the Table 8. The study showed that the protein content of the catfish (Clarias gariepinus) juveniles fed graded levels of diets containing Tiny Moss (Bryum capillare) were significantly different (P<0.05). The catfish fed T4 diet had the highest percentage level protein followed by T2, and T6 then T1, while T3 and T5 had the least protein. The average ether extract was also highest in T2 which were similar to those in T4, and T6, but were significantly different (P<0.05) to T1 and T3 which had the same protein level, whereas T5 had the least. The ash content, Nitrogen Free Extract, energy and glucose showed close similarities in the values such that they showed marginal variations which were not significantly different (P>0.05) among the individual groups.

Means with the same superscripts in the same column are not significantly different at P>0.05, while those with different superscripts in the same column are significantly different at same level.

The result of the effect of Tiny Moss (Bryum capillare) on Amino Acid Profile of Catfish Clarias gariepinus Juveniles fed diet containing Tiny Moss (Bryum capillare) is presented in the Table 9. The study showed that the Glutamic Acid, Aspartic Acid, Valine, Threonine, Serine, Phenylalanine, Proline and Methionine increased in value while Lysine, Leucine, Arginine, Alanine, Isoleucine, Glycine, Histidine and Tryptophan reduced in value and there was no significant change in cysteine (%) all were significantly at (P<0.05).

Means with the same superscripts in the same column are not significantly different at P>0.05, while those with different superscripts in the same column are significantly different at same level.

Figures 1-4 present the results of tissue analysis of fish from the respective treatment. Histological examinations of the test fish showed some pathological changes. The Tiny Moss (Bryum capillare) feed shows normal skin architecture with well outlined epithelia cell (EC) moderate effect on the skin layer with moderate necrosis (N) of the muscular region with the epithelia lining and superficial spreading of melanoma (M) restricted to the epidermis The heart shows normal cardiac tissue with cardiac cell (CC), cardiac fiber (CF) cardiac muscles (CM) shows moderate aggregate of myocardiac inflammation (AMI). The gill showed section of gill with ghost (G) appearance with severe aggregate of inflammatory cell (AIC). The liver cells revealed section of liver (X100) (H/E) shows severe effect on the hepatic tissue with severe I intra hepatic inflammation (IHI) and intra hepatic hemorrhage (IHIH). The damage done to these organs as the result of the feeds correlates with the concentrations of the feeds in each experimental tank.

Discussion

Non-conventional feed resources (NCFRs) are feeds that are not usually common in the markets and are not the traditional ingredients used for commercial fish feed production (Devendra, 1988; Madu et al., 2003). NCFRs are credited for being non-competitive in terms of human consumption, very cheap to purchase, by-products or waste products from agriculture, farm made feeds and processing industries and are able to serve as a form of waste management in enhancing good sanitation. The result of final total length of the Clarias gariepinus fed diets containing Tiny Moss (Bryum capillare) presented in Table 2 showed that there were significant (p<0.05) differences in the final total length during the period of the study. Though, the highest final total length was recorded among the T5, T3 and T1 respectively followed by T6 while T4 and T3 had similar records which were the least among the groups.

The result of proximate analysis of the fish diet containing Tiny Moss (Bryum capillare) in the diets as presented in the Table 3 showed varying levels of nutrients in diets containing Tiny Moss (Bryum capillare) for the experiment. The T6 diet had the highest percentage level of crude protein followed by T4 then T5 and T1, while T3 and T2 had the least crude protein. The crude fat was also highest in T6 followed by T4, T5, T1, T3 and T2 respectively. The crude fibre showed close similarities in the values such that they followed this trend; T2, T3, T1, T5, T4 and T6 respectively. The ash content, Moisture content Nitrogen Free Extract and Dry matter content equally showed little variations among the individual groups, this work is similar to the work of Elhassan et al., (2015) who reported a significant (p<0.05) increase in bambara groundnut protein (18.83±0.49), lipids (7.05±1.82), fiber (5.74±1.09), carbohydrate (63.37±2.57), moisture (12.59±1.14) and ash (3.52±0.22), which indicates that Bambara groundnut could be an excellent source of protein, lipid, carbohydrate and mineral elements in Clarias gariepinus Fed diets.

The relationship between Na and K as well as between Ca and P; are desirable with the respective ratios of Na/K (0.6) and Ca/P (1.2). They also contain high levels of carotenoids (30 to 41.5 mg/100g DW), vitamin C (137.5 to 197.5 mg/100g DW) [19].

Seventeen amino acids (isoleucine, leucine, lysine, methionine, cysteine, phenylalmine, tyrosine, threonine, valine, alanine, arginine, aspartic acid, glutamic acid, glycine, histidine, proline and serine) were detected. Their amino acid composition compare favourably with that of WHO/FAO protein standard indicating favourable nutritional balance except for lysine and methionine which appear marginal. The nutritional values of the phytochemicals were also assessed with a view of establishing and understanding their nutritional uses. The functional properties for the three vegetables were similar. Comparing the nutrient and chemical constituents with recommended dietary allowance (RDA) values, the results reveal that the leaves contain an appreciable amount of nutrients, minerals, vitamins, amino acids and phytochemicals and low levels of toxicants Essential or indispensable amino acids (EAAs) cannot be synthesised by fish and often remain inadequate but are needed for growth and tissue development [20,21]. The result of the effect of Tiny Moss (Bryum capillare) on Amino Acid Profile of Catfish Clarias Gariepinus Juveniles fed diet containing Tiny Moss (Bryum capillare) is presented in the Table 9. The study showed that the Glutamic Acid, Aspartic Acid, Valine, Threonine, Serine, Phenylalanine, Proline and Methionine increased in value while Lysine, Leucine, Arginine, Alanine Alanine, Isoleucine, Glycine, Histidine and Tryptophan reduced in value and there was no significant change in cysteine (%) all were significantly at (P<0.05).

Fishmeal is known to contain complete EAA profile that is needed to meet the protein requirement of most fish species. Since fishmeal is expensive as a feed ingredient, the use of non-conventional feedstuffs has been reported with good growth and better cost benefit values. The utilization of non-conventional feedstuffs of plant origin had been limited as a result of the presence of alkaloids, glycosides, oxalic acids, phytates, protease inhibitors, haematoglutinin, saponegin, momosine, cyanoglycosides, linamarin to mention a few despite their nutrient values and low-cost implications [22,23]. The report of this work is similar to the work of Sobowale et al. [19] who reported the nutritional components in three species of leafy vegetables using standard analytical methods. All the vegetables contained moisture (79.92 to 84.0%), crude protein (20.61 to 22.7%), crude fibre (10.7 to 22.44%), ash (6.8 to 10.44%), carbohydrate (55.86 to 68.22%) crude lipid (4.24 to 5.6%) and food energy (1507.19 to 1673.96 kJ/100g). The mineral element content were high with remarkable concentration of K (35.2 to 48.8mg/100g), Na (11.4 to 14.4 mg/100g), Ca (15.4 to 18.7mg/100g), Mg (12.2 to 18.7mg/100g), P (13.8 to 15.08mg/100g). These anti-nutritional factors negate growth and other physiological activities at higher inclusion levels [24].

The result of the essential amino acids indicated that these animal supplements could substitute fishmeal in fish feed (Table 2) since they all contain the required essential amino acids needed by fish for protein metabolism [25]. This result showed that earthworm meal is richer in methionine (Figure 1) than other animal protein sources studied which agreed with the observation of Finke (2003) when he compared the nutrient values in some invertebrates. Methionine has been credited as growth promoting essential amino acid, which is highly needed by cultured fish and limited in most plant and many animal supplements (Wilson, 2002).

Several reports have indicated that gill lesions do not only indicate possibilities of impaired respiratory functions but impaired osmo-regulatory functions as [26]. Even slight structural damage can render a fish vulnerable to osmo-regulatory as well as respiratory difficulties (Hughes and Morgan, 1973) thereby affecting the overall metabolism and survival of the fish. The histopathological alteration observed in the brain, gill, liver, intestine and muscle/flesh is an indication of the toxic effect of P. zeylanica extracts to fish. This agreed with Fafioye [27,28], observation when Clarias gariepinus and O. niloticus were exposed to lethal and sublethal concentrations of Parkia biglobosa and Raphia vinifera respectively. The gill lamellae play a significant role in regulating the exchange of gas, water and ions in fish. The role of the gill in excretion predisposes it in such a way that slight structural damage can render a fish very vulnerable to osmoregulation as well as respiratory difficulties.

Conclusion

Fish, like other organisms, required food (energy) in order to grow, survive and reproduce. The food items (source of energy) in aquatic habitat are in the form of plankton, periphyton, nueston, benthose, nekton and plants are available throughout the year. The success of intensive fish culture depends on the formulation of a fish feed that contains an optimum level of protein and energy necessary for the growth of fish and is also cheap. It is obviously necessary to formulate and manufacture fish feed from locally available feed ingredients. This type of feed prepared from such ingredients should serve as a source of essential amino acid, minerals, vitamins, growth promoting substances and energy [29-34].

Essential or indispensable amino acids (EAAs) cannot be synthesized by fish and often remain inadequate but are needed for growth and tissue development [21]. Fishmeal is known to contain complete EAA profile that is needed to meet the protein requirement of most fish species. Since fishmeal is expensive as a feed ingredient, the use of nonconventional feedstuffs has been reported with good growth and better cost benefit values. The utilization of nonconventional feedstuffs of plant origin had been limited as a result of the presence of alkaloids, glycosides, oxalic acids, phytates, protease inhibitors, haematoglutinin, saponegin, momosine, cyanoglycosides, linamarin to mention a few despite their nutrient values and low-cost implications [23].

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Advances in the Diagnosis and Management of Inflammatory Bowel Disease (IBD)- Juniper Publishers

Gastroenterology & Hepatology - Juniper Publishers

Abstract

Inflammatory bowel disease (IBD), comprising Crohn’s disease (CD) and ulcerative colitis (UC), poses substantial challenges in diagnosis and management due to its complex etiology and heterogeneous clinical manifestations. This review provides an updated synthesis of recent advancements in the field, focusing on diagnostic tools, biomarkers, imaging techniques, and novel therapeutic modalities. Diagnostic innovations include the utilization of biomarkers such as calprotectin and lactoferrin, which aid in distinguishing IBD from irritable bowel syndrome (IBS), and serological markers like ANCA and ASCA, which contribute to diagnostic accuracy. Emerging biomarkers under investigation hold promise for further improving diagnostic specificity and monitoring disease activity. Imaging techniques, such as magnetic resonance enterography (MRE), ultrasound elastography, and contrast-enhanced ultrasound, offer non-invasive options for evaluating disease extent and severity. Therapeutically, biologics have revolutionized IBD management with TNF inhibitors (e.g., infliximab, adalimumab), integrin inhibitors (e.g., vedolizumab), and IL-12/23 inhibitors (e.g., ustekinumab), each targeting specific pathways to achieve gut-selective immunosuppression. Small molecule inhibitors like JAK inhibitors (e.g., tofacitinib) and S1P receptor modulators (e.g., ozanimod) represent emerging therapeutic avenues with potential efficacy in refractory cases. Integrating personalized medicine approaches, including genetic profiling and microbiome analysis, holds promise for tailoring therapies to individual patient profiles, optimizing treatment outcomes and minimizing adverse effects. This comprehensive overview underscores the transformative impact of recent advancements in IBD diagnosis and management, paving the way for enhanced clinical decision-making and improved patient care in the evolving landscape of inflammatory bowel diseases.

Keywords: Inflammatory Bowel Disease; Crohn’s Disease; Ulcerative Colitis; Biomarkers; Imaging Techniques; Biologics

Abbreviations: IBD: Inflammatory Bowel Disease; IL: Interleukin; JAK: Janus Kinase; TYK 2: Tyrosine kinase 2; UC: Ulcerative colitis; S1P: Sphingosine-1-Phosphate; S1PR: Sphingosine-1-Phosphate Receptor; ANCA: Anti-Neutrophil Cytoplasmic Antibodies; ASCA: Anti-Saccharomyces Cerevisiae Antibodies; MRI: Magnetic Resonance Imaging; MRE: Magnetic Resonance Enterography; CT: Computed Tomography; CEUS: Contrast-Enhanced Ultrasound; CRP: C-reactive protein; CDAI: Crohn’s Disease Activity Index; CLE: Confocal Laser Endomicroscopy; DCE: Dye-based Chromoendoscopy; VCE: Virtual Electronic Chromoendoscopy; IBD5: Inflammatory Bowel Disease 5; NOD2/CARD15: Nucleotide-Binding Oligomerization Domain-containing Protein 2/Caspase Recruitment Domain-containing Protein 15; CTLA4: Cytotoxic T-Lymphocyte-associated Protein 4; ATG16L1: Autophagy-related 16-Like 1; TNF: Tumor Necrosis Factor; TNFα: Tumor Necrosis Factor alpha; IL-12: Interleukin-12; IL-23: Interleukin-23; IgG1κ: Immunoglobulin G1 Kappa Chain; Moab: Monoclonal Antibody; CD: Crohn’s Disease

Introduction

Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), represents a group of chronic, relapsing conditions of the gastrointestinal tract characterized by inflammation, mucosal damage, and a myriad of systemic manifestations. Affecting millions worldwide, IBD poses significant diagnostic and therapeutic challenges due to its heterogeneous presentation and variable disease course. The traditional diagnostic approach, relying heavily on clinical evaluation, endoscopy, and histopathology, is being supplemented by various innovative tools and techniques to enhance diagnostic accuracy and patient stratification. Concurrently, the therapeutic landscape of IBD has evolved remarkably, with the advent of biologics and small molecule inhibitors offering targeted and effective treatment options beyond conventional therapies [1-4]. This review aims to provide an updated overview of the latest advancements in diagnostic tools, biomarkers, and imaging techniques and highlight new treatment modalities shaping the future of IBD management.

Diagnostic Advances

Biomarkers

Calprotectin and Lactoferrin

Fecal Calprotectin (FCP) is a stool-based biomarker that detects gut inflammation non-invasively. It is predominantly located in neutrophil cytosol, and its expression increases during inflammation. Stool Lactoferrin (LF) is an iron-binding protein found within neutrophils. The level of lactoferrin released by neutrophils correlates with the severity of inflammation in the gastrointestinal tract. Testing for FCP and LF is highly beneficial in evaluating patients with vague GI symptoms like abdominal pain and diarrhea, especially when there are no alarming signs such as weight loss or GI bleeding. These symptoms could indicate functional issues like IBS or potentially IBD or GI infections. Low or normal levels of FCP or LF suggest inflammation or infection is unlikely, pointing towards a functional cause. Elevated levels, however, indicate a need for further investigation into IBD or infections using stool panel tests, colonoscopy, or both. Using these biomarkers to guide clinical decisions can reduce unnecessary testing and healthcare costs [5-8].

To aid in disease diagnosis, FCP was the pioneering stool biomarker capable of distinguishing between inflammatory and non-inflammatory gastrointestinal diseases. Several research studies in healthy individuals have recognized an FCP range typically falling between 10 - 50 μg/g, allowing slight variations based on the group under study and the specific assay employed [5-8]. If FCP levels exceed 50 μg/g on two separate occasions, it indicates a need for additional invasive tests such as colonoscopy or bowel imaging. Further elevated levels (>250 μg/g) may indicate an ongoing inflammatory process in the intestines. Research studying outcomes over 12 months for intermediate FCP levels (50-249 μg/g) found an 8% likelihood of developing IBD, compared to 1% for levels below 50 μg/g [9,10]. Similarly, a fecal lactoferrin level below 7.25 μg/g suggests no intestinal inflammation and points towards a functional cause like IBS in patients with GI symptoms. Elevated levels indicate inflammation with neutrophil infiltration in the intestinal mucosa, indicating IBD rather than IBS.

After diagnosing IBD initially, these biomarkers can also monitor disease activity and treatment effectiveness. In cases of IBS, where these markers typically remain normal, their absence of elevation can strengthen the diagnosis of a functional disorder. The International Organization for the Study of Inflammatory Bowel Disease has recommended a target FCP of <150 μg/g as a favorable treatment outcome [7]. Also, a few additional studies recommend a goal of <250 μg/g for both UC and CD as a prudent approach for the long term, which would be more sensible for physicians treating IBD outside specialist centers. With the discovery of these biomarkers, it has been feasible to monitor whether the inflammatory state has improved or resolved based on strategic tracking of their levels without the added burden of repeated colonoscopies for the patient [11-13].

Additionally, these biomarkers can assist in therapeutic drug monitoring for patients managed pharmacologically, enabling clinicians to make necessary medication adjustments by correlating with LF and FCP levels. These levels can also help assess the response to these adjustments and observe any improvements in disease outcomes. However, conducting an initial endoscopic assessment and comparing LF and FCP levels with the patient’s clinical features and endoscopic score is essential. Importantly, monitoring FCP and LF levels should never replace colonoscopy for colon cancer screening in IBD patients, which is recommended 8-10 years after their diagnosis or more frequently depending on their associated underlying pathologies [11-13].

Serological Markers

Serological markers like ANCA (anti-neutrophil cytoplasmic antibodies) and ASCA (anti-Saccharomyces cerevisiae antibodies) play a crucial role in diagnosing and classifying Inflammatory Bowel Disease (IBD), distinguishing between Crohn’s disease (CD) and ulcerative colitis (UC) [14-17].

ANCA: Based on their immunofluorescence patterns, ANCA can be categorized into perinuclear ANCA (pANCA) and cytoplasmic ANCA (cANCA). pANCA targets antigens like elastase, lactoferrin, and lysozyme found in neutrophil granules and colon epithelial cells, typically associated with UC. Conversely, cANCA is more prevalent in autoimmune vasculitides and less linked to IBD. pANCA positivity, especially when ASCA is negative, is more common in UC than CD, aiding differentiation when clinical and endoscopic findings are inconclusive. However, pANCA positivity is not specific to UC and can also occur in conditions such as primary sclerosing cholangitis and autoimmune hepatitis [14,15].

ASCA: ASCA refers to antibodies against various epitopes of Saccharomyces cerevisiae yeast. IgG ASCA is predominantly associated with CD, while IgA ASCA, although less studied, correlates with CD. ASCA positivity is more frequent in CD patients compared to UC or healthy individuals, showing high specificity but limited sensitivity. ASCA testing is beneficial in distinguishing CD from UC when diagnosis is uncertain based solely on clinical, endoscopic, and histological criteria [16,17].

Serological markers such as ANCA and ASCA are valuable for distinguishing between UC and CD, especially in cases with ambiguous clinical and endoscopic findings. ASCA positivity in CD is associated with specific clinical features such as structuring behavior and surgery risk, but its predictive accuracy varies. Unlike fecal biomarkers such as calprotectin, these markers are primarily used for diagnosis and are less frequently employed for monitoring disease activity or treatment response [14-17].

Emerging Biomarkers

The pursuit of novel biomarkers in inflammatory bowel disease (IBD) aims to enhance diagnostic precision, predict disease course, and tailor therapeutic strategies. Several emerging biomarkers show promise in these areas [18].

Fecal Volatile Organic Compounds (VOCs): These compounds are metabolic byproducts of gut microbiota and epithelial cells, detectable through non-invasive methods. Recent studies have demonstrated that specific patterns of fecal VOCs can differentiate IBD from other gastrointestinal disorders and may even distinguish between Crohn’s disease (CD) and ulcerative colitis (UC) [18].

MicroRNAs (miRNAs): These small, non-coding RNA molecules regulate gene expression and are found to be differentially expressed in IBD patients. Specific miRNAs, such as miR-21 and miR-155, have been identified as potential biomarkers for disease activity and response to therapy. Their stability in blood and stool makes them attractive candidates for non-invasive diagnostics [19].

Serum Proteins and Glycans: Advances in proteomics and glycomics have identified several serum proteins and glycan structures associated with IBD. For instance, glycoprotein acetylation (GlycA) levels correlate with inflammation and disease severity. Additionally, serum proteins like oncostatin M and its receptor have been linked to therapy-resistant IBD, providing insight into potential therapeutic targets [20].

Extracellular Vesicles (EVs): EVs, including exosomes, are membrane-bound particles released from cells that carry proteins, lipids, and nucleic acids. They play a role in intercellular communication and are increasingly recognized for their diagnostic potential. In IBD patients, EVs derived from intestinal epithelial cells and immune cells exhibit distinct molecular signatures that reflect disease state and activity [21].

Metabolomic Profiling: This approach involves comprehensively analyzing metabolites in biological samples. Metabolomic studies in IBD have identified alterations in pathways related to bile acids, amino acids, and short-chain fatty acids. Specific metabolites, such as tryptophan metabolites, are under investigation for their role in inflammation and as potential biomarkers for disease progression and treatment response [22].

These novel biomarkers hold great promise for transforming the diagnostic landscape of IBD, offering more precise and personalized approaches to managing this complex disease. Ongoing research and validation studies are crucial to bring these biomarkers into clinical practice.

Imaging Techniques

Magnetic Resonance Enterography (MRE)

Magnetic Resonance Enterography (MRE) is a non-invasive imaging technique that utilizes MRI technology to visualize and evaluate the small bowel. It involves the administration of oral and intravenous contrast agents to enhance the visualization of bowel wall anatomy and pathology, making it particularly suitable for assessing inflammatory bowel diseases like Crohn’s disease and ulcerative colitis [23,24].

One of the main benefits of MRE is the absence of ionizing radiation. Unlike computed tomography (CT), MRE does not expose patients to ionizing radiation, making it safer for repeated examinations, including in young patients and during pregnancy. Additionally, MRI provides high-resolution images with superior soft tissue contrast compared to CT, enabling detailed visualization of the bowel wall layers, mucosa, and surrounding structures. MRE allows the acquisition of images in multiple planes (axial, coronal, sagittal), providing a comprehensive evaluation of small bowel anatomy and pathology from various perspectives. It effectively assesses the extent and severity of inflammation in Crohn’s disease and ulcerative colitis, guiding clinicians in determining appropriate treatment strategies [23,24].

MRE is valuable for various applications in IBD. It complements endoscopy and histopathologic sampling in accurately diagnosing and staging Crohn’s disease, distinguishing between active inflammatory, fibro stenotic, and fistulizing phases. It helps differentiate disease phases in ulcerative colitis as well. MRE enables longitudinal assessment of disease activity and response to therapy over time, aiding in treatment planning and optimization. It is also valuable for detecting and characterizing complications such as strictures, fistulas, and abscesses, common in Crohn’s disease and may necessitate surgical intervention. Moreover, MRE provides detailed anatomical information essential for surgical planning, including mapping disease extent and identifying complications, thereby improving surgical outcomes. By integrating MRE findings with endoscopic and histopathologic data, clinicians better understand disease characteristics and tailor personalized treatment strategies accordingly [23,24]. In conclusion, Magnetic Resonance Enterography (MRE) is pivotal in managing inflammatory bowel disease (IBD), offering significant benefits such as superior imaging quality, absence of ionizing radiation, and detailed assessment of disease activity and complications. Its integration with other diagnostic modalities enhances accuracy in disease characterization and therapeutic decision-making, ultimately improving patient outcomes in IBD management.

Ultrasound Elastography: Non-invasive technique to assess bowel stiffness.

Ultrasound elastography is an advanced imaging technique that assesses tissue stiffness or elasticity by measuring the propagation of mechanical waves within the tissue. In the context of inflammatory bowel disease (IBD), ultrasound elastography specifically evaluates bowel wall stiffness, which can help distinguish between inflammatory and fibrotic changes in the gastrointestinal tract [25]. One of the primary benefits of ultrasound elastography is its ability to differentiate between tissue changes. This technique provides additional diagnostic information beyond traditional imaging modalities like ultrasound and magnetic resonance enterography (MRE). It helps clinicians differentiate between inflammatory activity and fibrotic changes within the bowel wall, which is crucial for treatment planning and monitoring disease progression. Another significant advantage is its non-invasive nature. Unlike invasive procedures such as biopsy, elastography offers a non-invasive means to assess bowel stiffness, making it suitable for frequent monitoring of disease activity and treatment response. Moreover, elastography enables real-time assessment of tissue stiffness during the ultrasound examination, offering immediate feedback to guide clinical decisions and therapeutic strategies. This technique also complements conventional ultrasound and MRE by adding functional information about tissue characteristics, enhancing the overall diagnostic accuracy in IBD management [25-27].

In the context of Crohn’s disease (CD), ultrasound elastography plays a critical role in identifying and quantifying bowel wall fibrosis. Fibrosis is a hallmark of chronic inflammation in CD, and early detection helps stratify patients for appropriate management strategies, including targeted therapy and surgical planning. By assessing changes in bowel wall stiffness over time, elastography aids in monitoring disease progression and treatment response in Crohn’s disease. It allows clinicians to evaluate the efficacy of medical therapies and make timely adjustments as needed. Additionally, elastography provides valuable preoperative information about the extent and severity of bowel wall fibrosis in cases requiring surgical intervention. This assists surgeons in planning optimal resection strategies and minimizing postoperative complications [26]. In ulcerative colitis (UC), although primarily affecting the mucosal layer, submucosal changes can occur that may alter tissue stiffness. Ultrasound elastography helps assess the extent of submucosal inflammation and its implications for disease management. Like in Crohn’s disease, elastography in ulcerative colitis facilitates the evaluation of treatment response by detecting changes in tissue stiffness associated with disease activity. It supports clinical decision-making by providing objective measures of therapeutic efficacy. Furthermore, elastography contributes to the phenotypic characterization of ulcerative colitis, aiding in differentiating disease subtypes based on severity and tissue involvement. This information guides personalized treatment approaches tailored to individual patient needs [25-27].

In conclusion, ultrasound elastography represents a promising advancement in managing inflammatory bowel disease, providing non-invasive assessment of bowel wall stiffness that complements traditional imaging modalities. Its ability to differentiate between inflammatory and fibrotic changes supports precise diagnosis, monitoring of disease activity, and treatment response evaluation in Crohn’s disease and ulcerative colitis. As technology evolves and research progresses, ultrasound elastography is poised to play an increasingly integral role in optimizing clinical outcomes and enhancing patient care in IBD.

Contrast-Enhanced Ultrasound (CEUS)

Contrast-enhanced ultrasound (CEUS) is an imaging technique that utilizes ultrasound contrast agents to enhance visualization of blood flow within tissues and organs. In inflammatory bowel disease (IBD), CEUS is crucial in assessing disease activity, distinguishing tissue types, and guiding therapeutic interventions [28]. CEUS provides real-time assessment of bowel wall vascularity, which correlates closely with inflammatory markers such as C-reactive protein (CRP) and clinical disease activity indices like the Crohn’s Disease Activity Index (CDAI). This capability allows clinicians to monitor disease progression and respond to treatment accurately. One of the significant challenges in managing Crohn’s disease (CD) is distinguishing between fibrotic strictures and inflammatory changes within the bowel wall. CEUS helps in this differentiation by assessing the degree of vascularization, which is critical for guiding treatment decisions. Fibrotic strictures may require surgical intervention, whereas inflammatory strictures may respond to medical therapy [26,28-30].

CEUS is highly effective in characterizing suspected abscesses in IBD patients, facilitating prompt therapeutic decisions such as drainage or antibiotic therapy. It also aids in visualizing the route and extent of fistula tracts in CD patients, providing valuable information for planning surgical interventions or monitoring treatment response. During treatment with biologic agents, CEUS can monitor changes in bowel wall enhancement, supporting clinicians in assessing treatment efficacy and making timely adjustments to therapy [29,30]. CEUS has demonstrated effectiveness comparable to magnetic resonance imaging (MRI) in assessing bowel wall vascularity and disease activity in CD, with additional advantages including real-time capability, costeffectiveness, and absence of ionizing radiation. It is particularly useful when MRI may be contraindicated or unavailable, such as in pregnant patients or those with claustrophobia. However, CEUS has limitations related to intestinal motility, affecting image quality and its restricted ability to evaluate specific bowel segments at a time, necessitating careful patient selection and consideration of complementary imaging modalities when needed [26-30].

In conclusion, contrast-enhanced ultrasound (CEUS) is emerging as a valuable adjunctive tool in the management of inflammatory bowel disease (IBD), particularly in Crohn’s disease (CD). Its ability to provide real-time assessment of bowel wall vascularity, differentiate between different tissue types, and guide therapeutic interventions makes it a promising modality in clinical practice. Further research and technological advancements are expected to expand the utility of CEUS and refine its applications in optimizing patient care and outcomes in IBD.

Endoscopic Innovations

Confocal Laser Endomicroscopy (CLE)

Mucosal healing, defined as restoring normal mucosal architecture and the absence of microscopic inflammation, holds significant clinical implications in managing inflammatory bowel disease (IBD). Studies have shown that achieving mucosal healing reduces hospitalization rates, surgery, and colorectal cancer, highlighting its pivotal role in disease modification and long-term prognosis [31]. Advanced imaging modalities and biomarkers have complemented traditional tools such as ileocolonoscopy and histology to accurately assess mucosal healing. Confocal laser endomicroscopy (CLE) has emerged as a promising technology due to its ability to provide real-time, high-resolution imaging of mucosal surfaces during endoscopy. CLE uses a low-power laser to illuminate tissues, allowing visualization at cellular and subcellular levels with up to 1000-fold magnification [31].

Indications for CLE include assessing mucosal barrier function, which plays a crucial role in evaluating intestinal mucosa integrity. It can detect subtle changes indicative of barrier dysfunction, such as epithelial cell shedding, impaired tight junctions, and apoptotic cell dropout. CLE is particularly useful for detecting subclinical inflammation and disease progression before visible changes on conventional endoscopy or symptoms occur in patients with IBD, where clinical symptoms may not fully reflect disease activity [31,32].

CLE also facilitates monitoring of response to therapy by enabling real-time assessment of treatment efficacy. It visualizes changes in mucosal healing and reduction of barrier defects, providing objective measures of disease activity that complement clinical symptoms and guide treatment decisions. Additionally, CLE is valuable in surveillance of high-risk patients, such as those with long-standing IBD or primary sclerosing cholangitis (PSC), for early detection of dysplasia and colorectal cancer [31,32]. Furthermore, CLE supports research into disease mechanisms and therapeutic interventions by offering detailed insights into mucosal structure and function. Its ability to enhance visualization and objectively assess mucosal integrity makes CLE a valuable adjunctive tool in gastroenterology, particularly in managing IBD. By facilitating early detection of mucosal changes and monitoring treatment response, CLE supports personalized medicine approaches to achieve and maintain mucosal healing, ultimately improving patient outcomes [31,32].

Chromoendoscopy

Colonoscopy has been the standard test for diagnosing inflammatory bowel disease (IBD) and a helpful diagnostic tool to guide treatment prognosis for mucosal healing. Recent advanced imaging techniques have become essential for endoscopists treating patients with IBD. Among these, dye-based and virtual chromoendoscopy, probe-based confocal laser endomicroscopy, and endocytoscopy stand out as innovative tools in clinical practice [33]. These technologies enable a more detailed and precise assessment of the bowel’s mucosal and vascular surfaces, approaching the histological examination level. Their role in diagnosing, predicting outcomes, and managing treatment for IBD and colitis-related cancer is becoming increasingly crucial for personalized medicine [34].

Chromoendoscopy is an advanced technique that improves the evaluation of intestinal mucosa and vascular patterns. There are two types of chromoendoscopy tests: dye-based chromoendoscopy (DCE) and virtual electronic chromoendoscopy (VCE). DCE uses staining agents such as methylene blue and indigo carmine to provide detailed mucosal characterization of the colon [34]. In contrast, VCE is a dye-free technique that utilizes light filters or post-processing algorithms to enhance the visualization of surface and vessel architecture [34]. Patients with IBD have an increased risk of developing colorectal cancer, with dysplasia often presenting as flat mucosal abnormalities. Therefore, precision endoscopy is essential for detecting these early lesions in the dysplasia-carcinoma pathway. DCE enhances the visibility of mucosal irregularities and lesion borders [34]. A recent metaanalysis revealed that DCE is more effective than white light endoscopy in detecting dysplasia [35].

New Treatment Modalities

Biologics

TNF Inhibitors

The pro-inflammatory cytokine TNFα has been identified as playing a vital role in the inflammatory cascade that causes chronic intestinal inflammation in inflammatory bowel disease. Synthetic anti-TNFα antibodies like infliximab and adalimumab Have been shown to mitigate this inflammatory process (Figure1). In addition, TNF initiatives have been shown to induce apoptosis of TNFα -producing immune cells, causing a reduced production of downstream pro-inflammatory cytokines from these and other cells [36]. Randomized control trials involving patients with ulcerative colitis have shown infliximab, Moab, and golli to be effective in inducing and maintaining clinical remission in patients with moderate to severe disease activity in whom conventional therapy has failed. Because TNF initiators interfere with the normal inflammatory response, they are contraindicated in patients with uncontrolled infections. Before initiating therapy, the patient should be screened for hepatitis B and evaluated for tuberculosis exposure [36].

Integrin Inhibitors

Vedolizumab (also known as MLN0002, LDP02, and MLN02) is a highly selective monoclonal antibody targeting the α4β7 integrin molecule. The α4β7integrin is a cell surface glycoprotein variably expressed on lymphocytes and is thought to be partly responsible for T-cell homing into lymphoid tissues in the gastrointestinal tract through its binding to the mucosal address in cell adhesion molecule (MAdCAM-1). These bound lymphocytes then migrate from the endothelium of the intestinal vasculature into the lamina propria and tissues, propagating inflammation (Figure 2). Higher levels of α4β7integrin and MAdCAM-1 are present in the colons of those with IBD than in patients with irritable bowel syndrome. It is also thought that there are lower numbers of T-lymphocytes with the α4β7 integrin circulating in the peripheral blood in patients with colonic inflammation. As these agents are considered “gut selective,” the α4β7 integrin molecules provide an opportunity to attenuate the pathological gut inflammation seen in patients with IBD [37,38].

IL-12/23 Inhibitors

Ustekinumab (UST) is a fully human IgG1κ monoclonal antibody that inhibits the p40 subunit shared by the proinflammatory cytokines, the interleukin (IL)-12 and -23. This blockade dampens the inflammatory cascade and differentiation of inflammatory T cells. It is currently approved for several immune-mediated diseases, such as moderate to severe plaque psoriasis, psoriatic arthritis, and Crohn’s disease, and has shown promising results in UC [39].

Small Molecule Inhibitors

JAK Inhibitors

As novel therapeutic drugs, JAK inhibitors can block multiple signaling pathways. The JAK family kinases JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK 2) target a variety of cytokine pathways through cytokine receptors. Tofacitinib is an oral small-molecule JAK inhibitor that can inhibit all JAKs, preferentially JAK1 and JAK3. The efficacy of tofacitinib for treating moderate to severe active UC has been approved [40,41].

Unlike biological monoclonal antibodies, JAK inhibitors are characterized by a rapid onset of action and a very short half-life (5-6 h), making them potentially more straightforward to manage, especially in the event of infections [40,41]. .

S1P Receptor Modulators

S1P is a lipid mediator that is derived from membrane sheath lipid metabolism. Ozanimod is an oral and selective S1PR modulator that acts on S1PR-1 and S1PR-5. It induces peripheral blood lymphocytes to isolate in the lymph nodes, thereby reducing the number of activated lymphocytes circulating to the inflammatory sites [40,41].

Personalized Medicine in IBD

Genetic profiling

Genetic profiling in personalized medicine for Inflammatory Bowel Disease (IBD) enhances the utilization of genomic data to foster treatment strategies. Kim et al. discussed that the analysis of variations in gene polymorphism like NOD2/CARD15, IBD5, CTLA4, IL23R, and ATG16L1 enables clinicians in the prediction of disease susceptibility, severity and response to therapies [44]. For instance, genetic markers guide the use of biologics such as anti-TNF agents in Crohn’s disease and ulcerative colitis [42-44]. Recent studies highlight the role of personalized medicine in improving patient outcomes and reducing adverse effects through targeted therapies [43-45]. This approach underscores the shift towards precision medicine, optimizing treatment efficacy and patient quality of life.

Microbiome analysis

Microbiome analysis is crucial in personalized Inflammatory Bowel Disease (IBD) medicine. It assesses the composition of gut microbiota to predict treatment responses. Variations in microbial organisms and specific taxa, such as Faecalibacterium prausnitzii, can influence disease progression and therapeutic outcomes, known as healthy bacteria [46]. The microbiome helps guide antibiotics, probiotics, and fecal microbiota systemic modulation. Recent studies highlight the impact of the microbiome on IBD pathogenesis and treatment efficacy. This approach emphasizes the integration of microbiome data into clinical practice, enhancing treatment precisions and patient management processes and demonstrating treatment efficacy. Hence, microbiome analysis elucidates the intricacy of integrating microbiome data into clinical practice to improve treatment precision and patient management strategies [47,48].

Future Directions and Research

Novel Therapies: Potential Future Biologics and Small Molecules

The landscape of IBD treatment continues to evolve with ongoing research into novel biologics and small molecules targeting specific pathways in disease pathogenesis. Potential biologics under investigation include therapies that aim to modulate novel inflammatory cytokines or pathways, such as IL- 23, IL-6, or JAK inhibitors. For instance, agents targeting the IL-23/ IL-17 axis have shown promise in clinical trials for Crohn’s disease and ulcerative colitis, demonstrating efficacy in patients refractory to conventional therapies. Small molecules such as sphingosine- 1-phosphate receptor modulators and RORγt inhibitors are also being explored for their potential to provide oral alternatives with targeted mechanisms of action. These advancements hold promise for expanding treatment options and improving outcomes for patients with refractory or aggressive forms of IBD.

Combination Therapies: Benefits and Risks of Combining Different Therapeutic Approaches

Combination therapy in IBD involves utilizing multiple agents with complementary mechanisms of action to achieve synergistic therapeutic effects. This approach aims to enhance efficacy, induce and maintain remission, and reduce the risk of developing drug resistance or side effects associated with monotherapy. Biologic therapies, such as anti-TNF agents, are often combined with immunomodulators like thiopurines or methotrexate to optimize response rates and durability of remission. However, using combination therapies requires careful consideration of potential risks, including increased susceptibility to infections and malignancies, cost implications, and patient adherence. Future research must refine treatment algorithms, identify biomarkers to predict response to combination therapies and optimize safety profiles to maximize benefits while minimizing risks.

Precision Medicine: Future of Personalized Treatment Strategies in IBD

The concept of precision medicine aims to tailor therapeutic interventions based on individual patient characteristics, including genetic, environmental, and microbiological factors. Advances in genomic profiling have identified genetic variants associated with IBD susceptibility, disease phenotype, and response to therapy, paving the way for personalized treatment strategies. Biomarkerdriven approaches, such as measuring serum cytokine profiles or gut microbiota composition, hold promise in predicting disease course and therapeutic response. Integrating these insights into clinical practice could enable clinicians to stratify patients into subgroups with distinct pathogenic mechanisms and tailor therapies accordingly. Precision medicine approaches include advanced imaging techniques, such as molecular imaging or functional MRI, to monitor disease activity and guide real-time treatment decisions. While challenges remain in translating these discoveries into clinical practice, ongoing research initiatives, and collaborative efforts are crucial in realizing the full potential of precision medicine in optimizing outcomes for patients with IBD [49,50].

Conclusion

The field of inflammatory bowel disease (IBD) has seen remarkable progress in diagnosis and management. Advances in diagnostic tools, such as biomarkers like calprotectin and lactoferrin, serological markers like ANCA and ASCA, and innovative imaging techniques, including magnetic resonance enterography and ultrasound elastography, are enhancing our ability to diagnose and monitor IBD with greater precision and less invasiveness. Moreover, the advent of biologics such as TNF, integrin, and IL-12/23 inhibitors, alongside promising small molecule inhibitors like JAK inhibitors and S1P receptor modulators, represents a significant shift towards personalized and targeted therapies. Looking ahead, personalized medicine in IBD, driven by genetic profiling and microbiome analysis, promises to optimize treatment outcomes and minimize adverse effects. The future landscape of IBD management appears poised to integrate novel therapies and explore combination strategies, further advancing our ability to tailor treatments to individual patient needs. These advancements not only underscore the ongoing evolution in clinical practice but also offer hope for improved outcomes and quality of life for individuals living with IBD. As research expands and new therapies emerge, collaboration across disciplines will be essential in realizing the full potential of these innovations in the fight against IBD.

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