Gut microbiota plays a significant role in gout.

With the development of social economy, the incidence of gout is increasing, which is closely related to people's increasingly rich diet. Eating a diet high in purine, fat, sugar and low-fibre for a long time further aggravates gout by affecting uric acid metabolism. The renal metabolism mechanism of uric acid has been thoroughly studied. To find a new treatment method for gout, increasing studies have recently been conducted on the mechanism of intestinal excretion, metabolism and absorption of uric acid. The most important research is the relationship between intestinal microbiota and the risk of gout. Gut microbiota represent bacteria that reside in a host's gastrointestinal tract. The composition of the gut microbiota is associated with protection against pathogen colonization and disease occurrence. This review focuses on how gut microbiota affects gout through uric acid and discusses the types of bacteria that may be involved in the occurrence and progression of gout. We also describe potential therapy for gout by restoring gut microbiota homeostasis and reducing uric acid levels. We hold the perspective that changing intestinal microbiota may become a vital method for effectively preventing or treating gout.

Charting the cellular biogeography in colitis reveals fibroblast trajectories and coordinated spatial remodeling.

Gut inflammation involves contributions from immune and non-immune cells, whose interactions are shaped by the spatial organization of the healthy gut and its remodeling during inflammation. The crosstalk between fibroblasts and immune cells is an important axis in this process, but our understanding has been challenged by incomplete cell-type definition and biogeography. To address this challenge, we used multiplexed error-robust fluorescence in situ hybridization (MERFISH) to profile the expression of 940 genes in 1.35 million cells imaged across the onset and recovery from a mouse colitis model. We identified diverse cell populations, charted their spatial organization, and revealed their polarization or recruitment in inflammation. We found a staged progression of inflammation-associated tissue neighborhoods defined, in part, by multiple inflammation-associated fibroblasts, with unique expression profiles, spatial localization, cell-cell interactions, and healthy fibroblast origins. Similar signatures in ulcerative colitis suggest conserved human processes. Broadly, we provide a framework for understanding inflammation-induced remodeling in the gut and other tissues.

p53 promotes revival stem cells in the regenerating intestine after severe radiation injury.

Ionizing radiation induces cell death in the gastrointestinal (GI) epithelium by activating p53. However, p53 also prevents animal lethality caused by radiation-induced acute GI syndrome. Through single-cell RNA-sequencing of the irradiated mouse small intestine, we find that p53 target genes are specifically enriched in regenerating epithelial cells that undergo fetal-like reversion, including revival stem cells (revSCs) that promote animal survival after severe damage of the GI tract. Accordingly, in mice with p53 deleted specifically in the GI epithelium, ionizing radiation fails to induce fetal-like revSCs. Using intestinal organoids, we show that transient p53 expression is required for the induction of revival stem cells and is controlled by an Mdm2-mediated negative feedback loop. Together, our findings reveal that p53 suppresses severe radiation-induced GI injury by promoting fetal-like reprogramming of irradiated intestinal epithelial cells.

Vitamin D3 Bioaccessibility from Supplements and Foods-Gastric pH Effect Using a Static In Vitro Gastrointestinal Model.

Vitamin D3 deficiency is a global phenomenon, which can be managed with supplementation and food fortification. However, vitamin D3 bioaccessibility may depend on factors such as matrix composition and interactions throughout the gastrointestinal (GI) tract. This research focused on the effect of different matrices on vitamin D3 content during digestion, as well as the effect of pH on its bioaccessibility. The INFOGEST protocol was employed to simulate digestion. Three different types of commercial supplements, two foods naturally rich in vitamin D3, and three fortified foods were investigated. High-Performance Liquid Chromatography was used to determine the initial vitamin D3 content in the supplements and foods, as well as after each digestion stage. The results indicate that the foods exhibited higher bioaccessibility indices compared to the supplements and a higher percentage retention at the end of the gastric phase. The pH study revealed a positive correlation between an increased gastric pH and the corresponding content of vitamin D3. Interestingly, exposing the matrix to a low pH during the gastric phase resulted in an increased intestinal content of D3. Vitamin D3 is more bioaccessible from foods than supplements, and its bioaccessibility is susceptible to changes in gastric pH. Fasting conditions (i.e., gastric pH = 1) enhance the vitamin's bioaccessibility.

Clinical Analysis and in Vitro Correlation of BCRP-Mediated Drug-Drug Interaction in the Gastrointestinal Tract.

Breast cancer resistance protein (BCRP) is a drug efflux transporter expressed on the epithelial cells of the small intestine and on the lateral membrane of the bile duct in the liver; and is involved in the efflux of substrate drugs into the gastrointestinal lumen and secretion into bile. Recently, the area under the plasma concentration-time curve (AUC) of rosuvastatin (ROS), a BCRP substrate drug, has been reported to be increased by BCRP inhibitors, and BCRP-mediated drug-drug interaction (DDI) has attracted attention. In this study, we performed a ROS uptake study using human colon cancer-derived Caco-2 cells and confirmed that BCRP inhibitors significantly increased the intracellular accumulation of ROS. The correlation between the cell to medium (C/M) ratio of ROS obtained by the in vitro study and the absorption rate constant (ka) ratio obtained by clinical analysis was examined, and a significant positive correlation was observed. Therefore, it is suggested that the in vitro study using Caco-2 cells could be used to quantitatively estimate BCRP-mediated DDI with ROS in the gastrointestinal tract.

Thermal stability and in vitro biological fate of lactoferrin-polysaccharide complexes.

Lactoferrin (LF) is a thermally sensitive iron-binding globular glycoprotein. Heat treatment can induce its denaturation and aggregation and thus affect its functional activity. In this study, carrageenan (CG), xanthan gum (XG) and locust bean gum (LBG), allowed to apply in infant food, were used to form protein-polysaccharide complexes to improve the thermal stability of LF. Meanwhile, in vitro simulated infant digestion and absorption properties of LF were also estimated. The results showed that the complexes formed by CG and XG with LF (LF-CG and LF-XG) could significantly inhibit the loss of α-helix structure of LF against heating. LF-CG and LF-LBG could protect LF from digestion in simulated infant gastric fluid and slow down the degradation of LF under the simulated intestinal conditions. Besides, LF, LF-CG and LF-XG showed no adverse effects on the growth of Caco-2 cells in the LF concentration range of 10-300 µg/mL, and LF-XG exhibited better beneficial to improve the cell uptake of the digestive product than the other protein-polysaccharides at the LF concentration of 100 µg/mL. This study may provide a reference for the enhancement of thermal processing stability of LF and development infant food ingredient with high nutrients absorption efficiency in the gastrointestinal environment in the future.

Coordinated ASBT and EGFR Mechanisms for Optimized Liraglutide Nanoformulation Absorption in the GI Tract.

Background: For maintenance therapy in type 2 diabetes, glucagon-like peptide-1 agonist (GLP-1A), which exhibits low cardiovascular risk and high efficacy, is a promising peptide therapeutic. However, developing an oral GLP-1A presents challenges due to the analog's poor cellular permeability and gastrointestinal (GI) stability. Methods: To mitigate such limitations, an oral nanoformulation of liraglutide (LG) was designed and achieved by combining LG with bile acid derivatives using the nanoprecipitation method. This strategy allowed the bile acid moieties to localize at the nanoparticle surface, enhancing the binding affinity for apical sodium-dependent bile acid transporter (ASBT) and improving GI stability. The in vitro characteristics, cellular permeability, and absorption mechanisms of the LG nanoformulation (LG/TD-NF) were thoroughly investigated. Furthermore, the in vivo oral absorption in rats and the glucose-lowering effects in a diabetic (db/db) mouse model were evaluated. Results: The LG/TD-NF produced neutral nanoparticles with a diameter of 58.7 ± 4.3 nm and a zeta potential of 4.9 ± 0.4 mV. Notably, when exposed to simulated gastric fluid, 65.7 ± 3.6% of the LG/TD-NF remained stable over 120 min, while free LG was fully degraded. Relative to unformulated LG, the Caco-2 cellular permeability of the nanoformulation improved, measuring 10.9 ± 2.1 (× 10-6 cm/s). The absorption mechanism prominently featured endocytosis simultaneously mediated by both ASBT and epidermal growth factor receptor (EGFR). The oral bioavailability of the LG/TD-NF was determined to be 3.62% at a dosage of 10 mg/kg, which is 45.3 times greater than that of free LG. In a diabetes model, LG/TD-NF at 10 mg/kg/day exhibited commendable glucose sensitivity and reduced HbA1c levels by 4.13% within 28 days, similar to that of subcutaneously administered LG at a dosage of 0.1 mg/kg/day. Conclusion: The oral LG/TD-NF promotes ASBT/EGFR-mediated transcytosis and assures cellular permeability within the GI tract. This method holds promise for the development of oral GLP-1A peptides as an alternative to injections, potentially enhancing patient adherence to maintenance therapy.

Insights into midgut cell types and their crucial role in antiviral immunity in the lepidopteran model Bombyx mori.

The midgut, a vital component of the digestive system in arthropods, serves as an interface between ingested food and the insect's physiology, playing a pivotal role in nutrient absorption and immune defense mechanisms. Distinct cell types, including columnar, enteroendocrine, goblet and regenerative cells, comprise the midgut in insects and contribute to its robust immune response. Enterocytes/columnar cells, the primary absorptive cells, facilitate the immune response through enzyme secretions, while regenerative cells play a crucial role in maintaining midgut integrity by continuously replenishing damaged cells and maintaining the continuity of the immune defense. The peritrophic membrane is vital to the insect's innate immunity, shielding the midgut from pathogens and abrasive food particles. Midgut juice, a mixture of digestive enzymes and antimicrobial factors, further contributes to the insect's immune defense, helping the insect to combat invading pathogens and regulate the midgut microbial community. The cutting-edge single-cell transcriptomics also unveiled previously unrecognized subpopulations within the insect midgut cells and elucidated the striking similarities between the gastrointestinal tracts of insects and higher mammals. Understanding the intricate interplay between midgut cell types provides valuable insights into insect immunity. This review provides a solid foundation for unraveling the complex roles of the midgut, not only in digestion but also in immunity. Moreover, this review will discuss the novel immune strategies led by the midgut employed by insects to combat invading pathogens, ultimately contributing to the broader understanding of insect physiology and defense mechanisms.

Bacterial communities along parrot digestive and respiratory tracts: the effects of sample type, species and time / Comunidades bacterianas a lo largo del tracto digestivo y respiratorio de los loros: los efectos del tipo de muestra, especie y tiempo

Digestive and respiratory tracts are inhabited by rich bacterial communities that can vary between their different segments. In comparison with other bird taxa with developed caeca, parrots that lack caeca have relatively lower variability in intestinal morphology. Here, based on 16S rRNA metabarcoding, we describe variation in microbiota across different parts of parrot digestive and respiratory tracts both at interspecies and intraspecies levels. In domesticated budgerigar (Melopsittacus undulatus), we describe the bacterial variation across eight selected sections of respiratory and digestive tracts, and three non-destructively collected sample types (faeces, and cloacal and oral swabs). Our results show important microbiota divergence between the upper and lower digestive tract, but similarities between respiratory tract and crop, and also between different intestinal segments. Faecal samples appear to provide a better proxy for intestinal microbiota composition than the cloacal swabs. Oral swabs had a similar bacterial composition as the crop and trachea. For a subset of tissues, we confirmed the same pattern also in six different parrot species. Finally, using the faeces and oral swabs in budgerigars, we revealed high oral, but low faecal microbiota stability during a 3-week period mimicking pre-experiment acclimation. Our findings provide a basis essential for microbiota-related experimental planning and result generalisation in non-poultry birds.(AU)

Non-electrophysiological techniques targeting transient receptor potential (TRP) gene of gastrointestinal tract.

Transient receptor potential (TRP) channels are cation channels related to a wide range of physical and chemical stimuli, they are expressed all along the gastrointestinal system, and a myriad of diseases are often associated with aberrant expression or mutation of the TRP gene, suggesting that TRPs are promising targets for drug therapy. Therefore, a better understanding of the information of TRPs in health and disease could facilitate the development of effective drugs for the treatment of gastrointestinal diseases like IBD. But there are very few generalizations about the experimental techniques studied in this field. In view of the promise of TRP as a therapeutic target, we discuss experimental methods that can be used for TRPs including their distribution, function and interaction with other proteins, as well as some promising emerging technologies to provide experimental methods for future studies.

Impact of Whey Protein Corona Formation around TiO2 Nanoparticles on Their Physiochemical Properties and Gastrointestinal Fate.

Previously, we found that whey proteins form biomolecular coronas around titanium dioxide (TiO2) nanoparticles. Here, the gastrointestinal fate of whey protein-coated TiO2 nanoparticles and their interactions with gut microbiota were investigated. The antioxidant activity of protein-coated nanoparticles was enhanced after simulated digestion. The structure of the whey proteins was changed after they adsorbed to the surfaces of the TiO2 nanoparticles, which reduced their hydrolysis under simulated gastrointestinal conditions. The presence of protein coronas also regulated the impact of the TiO2 nanoparticles on colonic fermentation, including promoting the production of short-chain fatty acids. Bare TiO2 nanoparticles significantly increased the proportion of harmful bacteria and decreased the proportion of beneficial bacteria, but the presence of protein coronas alleviated this effect. In particular, the proportion of beneficial bacteria, such as Bacteroides and Bifidobacterium, was enhanced for the coated nanoparticles. Our results suggest that the formation of a whey protein corona around TiO2 nanoparticles may have beneficial effects on their behavior within the colon. This study provides valuable new insights into the potential impact of protein coronas on the gastrointestinal fate of inorganic nanoparticles.

Phenolic Compounds from Apples: From Natural Fruits to the Beneficial Effects in the Digestive System.

Conditions in the gastrointestinal tract and microbial metabolism lead to biotransformation of parent, native phenolic compounds from apples into different chemical forms. The aim of this work was to review current knowledge about the forms of phenolic compounds from apples in the gastrointestinal tract and to connect it to their potential beneficial effects, including the mitigation of health problems of the digestive tract. Phenolic compounds from apples are found in the gastrointestinal tract in a variety of forms: native (flavan-3-ols, phenolic acids, flavonols, dihydrochalcones, and anthocyanins), degradation products, various metabolites, and catabolites. Native forms can show beneficial effects in the stomach and small intestine and during the beginning phase of digestion in the colon. Different products of degradation and phase II metabolites can be found in the small intestine and colon, while catabolites might be important for bioactivities in the colon. Most studies connect beneficial effects for different described health problems to the whole apple or to the amount of all phenolic compounds from apples. This expresses the influence of all native polyphenols from apples on beneficial effects. However, further studies of the peculiar compounds resulting from native phenols and their effects on the various parts of the digestive tract could provide a better understanding of the specific derivatives with bioactivity in humans.

A Novel Drosophila Model of Alzheimer's Disease to Study Aß Proteotoxicity in the Digestive Tract.

Amyloid-ß (Aß) proteotoxicity is associated with Alzheimer's disease (AD) and is caused by protein aggregation, resulting in neuronal damage in the brain. In the search for novel treatments, Drosophila melanogaster has been extensively used to screen for anti-Aß proteotoxic agents in studies where toxic Aß peptides are expressed in the fly brain. Since drug molecules often are administered orally there is a risk that they fail to reach the brain, due to their inability to cross the brain barrier. To circumvent this problem, we have designed a novel Drosophila model that expresses the Aß peptides in the digestive tract. In addition, a built-in apoptotic sensor provides a fluorescent signal from the green fluorescent protein as a response to caspase activity. We found that expressing different variants of Aß1-42 resulted in proteotoxic phenotypes such as reduced longevity, aggregate deposition, and the presence of apoptotic cells. Taken together, this gut-based Aß-expressing fly model can be used to study the mechanisms behind Aß proteotoxicity and to identify different substances that can modify Aß proteotoxicity.

Gastrointestinal hormones: History, biology, and measurement.

This chapter attempts to provide an all-round picture of a dynamic and major branch of modern endocrinology, i.e. the gastrointestinal endocrinology. The advances during the last half century in our understanding of the dimensions and diversity of gut hormone biology - inside as well as outside the digestive tract - are astounding. Among major milestones are the dual brain-gut relationship, i.e. the comprehensive expression of gastrointestinal hormones as potent transmitters in central and peripheral neurons; the hormonal signaling from the enteroendocrine cells to the brain and other extraintestinal targets; the role of gut hormones as growth and fertility factors; and the new era of gut hormone-derived drugs. Accordingly, gastrointestinal hormones have pathogenetic roles in major metabolic disorders (diabetes mellitus and obesity); in tumor development (common cancers, sarcomas, and neuroendocrine tumors); and in cerebral diseases (anxiety, panic attacks, and probably eating disorders). Such clinical aspects require accurate pathogenetic and diagnostic measurements of gastrointestinal hormones - an obvious responsibility for clinical chemistry/biochemistry. In order to obtain a necessary insight into today's gastrointestinal endocrinology, the chapter will first describe the advances in gastrointestinal endocrinology in a historical context. The history provides a background for the subsequent description of the present biology of gastrointestinal hormones, and its biomedical consequences - not least for clinical chemistry/biochemistry with its specific responsibility for selection of appropriate assays and reliable measurements.

Bacteriocins: Curial guardians of gastrointestinal tract.

The human gastrointestinal (GI) tract microbiome secretes various metabolites that play pivotal roles in maintaining host physiological balance and influencing disease progression. Among these metabolites, bacteriocins-small, heat-stable peptides synthesized by ribosomes-are notably prevalent in the GI region. Their multifaceted benefits have garnered significant interest in the scientific community. This review comprehensively explores the methods for mining bacteriocins (traditional separation and purification, bioinformatics, and artificial intelligence), their effects on the stomach and intestines, and their complex bioactive mechanisms. These mechanisms include flora regulation, biological barrier restoration, and intervention in epithelial cell pathways. By detailing each well-documented bacteriocin, we reveal the diverse ways in which bacteriocins interact with the GI environment. Moreover, the future research direction is prospected. By further studying the function and interaction of intestinal bacteriocins, we can discover new pharmacological targets and develop drugs targeting intestinal bacteriocins to regulate and improve human health. It provides innovative ideas and infinite possibilities for further exploration, development, and utilization of bacteriocins. The inevitable fact is that the continuously exploration of bacteriocins is sure to bring the promising future for demic GI health understanding and interference strategy.

The search for gastrointestinal inflammation in autism: a systematic review and meta-analysis of non-invasive gastrointestinal markers.

BACKGROUND: Gastrointestinal symptoms and inflammatory gastrointestinal diseases exist at higher rates in the autistic population. It is not clear however whether autism is associated with elevated gastrointestinal inflammation as studies examining non-invasive faecal biomarkers report conflicting findings. To understand the research landscape and identify gaps, we performed a systematic review and meta-analysis of studies measuring non-invasive markers of gastrointestinal inflammation in autistic and non-autistic samples. Our examination focused on faecal biomarkers as sampling is non-invasive and these markers are a direct reflection of inflammatory processes in the gastrointestinal tract. METHODS: We extracted data from case-control studies examining faecal markers of gastrointestinal inflammation. We searched PubMed, Embase, Cochrane CENTRAL, CINAHL, PsycINFO, Web of Science Core Collection and Epistemonikos and forward and backwards citations of included studies published up to April 14, 2023 (PROSPERO CRD42022369279). RESULTS: There were few studies examining faecal markers of gastrointestinal inflammation in the autistic population, and many established markers have not been studied. Meta-analyses of studies examining calprotectin (n = 9) and lactoferrin (n = 3) were carried out. A total of 508 autistic children and adolescents and 397 non-autistic children and adolescents were included in the meta-analysis of calprotectin studies which found no significant group differences (ROM: 1.30 [0.91, 1.86]). Estimated differences in calprotectin were lower in studies with siblings and studies which did not exclude non-autistic controls with gastrointestinal symptoms. A total of 139 autistic participants and 75 non-autistic controls were included in the meta-analysis of lactoferrin studies which found no significant group differences (ROM: 1.27 [0.79, 2.04]). LIMITATIONS: All studies included in this systematic review and meta-analysis examined children and adolescents. Many studies included non-autistic controls with gastrointestinal symptoms which limit the validity of their findings. The majority of studies of gastrointestinal inflammation focused on children under 12 with few studies including adolescent participants. Most studies that included participants aged four or under did not account for the impact of age on calprotectin levels. Future studies should screen for relevant confounders, include larger samples and explore gastrointestinal inflammation in autistic adolescents and adults. CONCLUSIONS: There is no evidence to suggest higher levels of gastrointestinal inflammation as measured by calprotectin and lactoferrin are present in autistic children and adolescents at the population level. Preliminary evidence suggests however that higher calprotectin levels may be present in a subset of autistic participants, who may be clinically characterised by more severe gastrointestinal symptoms and higher levels of autistic traits.

The kinetics of amino acid disappearance in the small intestine is related to the extent of amino acids absorbed in growing pigs.

This study evaluated the importance of a correction for amino acids (AA) released into the hindgut on a measure of AA absorption kinetics and tested whether AA absorption kinetics are related to the extent of AA absorption using the growing pig as a model for humans. Thirty-six nine-week-old pigs (22·3 kg) received a diet containing whey protein as the sole protein source for 8 d. Pigs received their last meal containing the indigestible marker titanium dioxide before being euthanised at 1, 2, 3, 4, 6 and 12 h post-feeding. The entire content of each gastrointestinal tract (GIT) region was collected to determine AA released into the hindgut, and the kinetics and extent of AA absorption (uncorrected and corrected for AA entering the hindgut). Amounts of AA released into the hindgut increased over time (e.g. 33 and 180 mg of Glu for 4 and 6 h post-feeding). The corrected apparent amount of each AA absorbed from the GIT lumen after 4 h post-feeding was generally lower (P ≤ 0·05) than the uncorrected counterpart. Differences in both the kinetics and extent of AA absorption were observed across AA. For example, the time to reach half of the apparent AA absorption (T50) was 1·5 and 3·4 h for Met and Arg, respectively, whereas their extent of apparent absorption was 93 and 73 %. Negative correlations between parameters related to kinetics and the extent of apparent absorption were observed (e.g. for T50 r = -0·81; P < 0·001). The kinetics of AA absorption is related to the extent of AA absorption.

Gastrointestinal delivery of codfish Skin-Derived collagen Hydrolysates: Deep eutectic solvent extraction and bioactivity analysis.

The fishing industry produces substantial by-products, such as heads, skins, bones, and scales, rich in collagen-a prevalent protein in these materials. However, further application of deep eutectic solvent-based extraction remains unexplored. In this study, we extracted collagen with urea: propanoic acid mixture (U:PA; 1:2) with a 2.2 % yield, followed by enzymatic hydrolysis with alcalase for 120 min. The resulting bioactive peptides demonstrated notable antioxidant activity (961 µmol TE) and antihypertensive properties (39.3 % ACE inhibition). Subsequently, we encapsulated 39.3 % of these hydrolysates in chitosan-TPP capsules, which released about 58 % of their content, primarily in the intestine, as mimicked in the in vitro model of the gastrointestinal tract. Although the digestion process did not significantly alter the size of the non-encapsulated collagen peptides, it did influence their health benefits. The promising results suggest that further research could optimize the use of collagen from fish by-products, potentially offering a sustainable source for health products.

Stability and gastrointestinal behavior of curcumin-loaded emulsion stabilized by multi-conformation soy proteins: Influence of oil volume fraction.

The aim of this work was to assess the potential of nanoemulsions stabilized by mixed soy protein with multi-conformation as curcumin carrier, and the influence of oil volume fraction on stability and gastrointestinal behavior of curcumin-loaded emulsion was investigated. Loading efficiency showed a slight increase with higher oil content, though the difference was not statistically significant. With the increase of oil, the viscosity (Pa‧s), thixotropy (area of hysteresis loop) and particle size of the emulsion increased, which facilitated the physical and chemical stability of curcumin-loaded emulsion. However, the free fatty acid release rate and bioaccessibility of curcumin was negatively correlated with the oil volume fraction and the particle size of emulsion after gastric digestion. Notably, the digestion in stomach did not affect the structure of interfacial protein, demonstrating that protein-based nanoemulsions exhibited resistance to gastric digestion. This study provides theoretical guidance for the application of protein-based emulsion in curcumin delivery.

Possible role of neuropeptide Y on zymosan- and lipopolysaccharide-induced change in gastrointestinal feed passage via the medulla oblongata in chicks.

Zymosan is a fungi-derived pathogen-associated molecular pattern. It activates the immune system and induces the reduction of feed passage rate in the gastrointestinal tract of vertebrates including birds. However, the mechanism mediating the zymosan-induced inhibition of feed passage in the gastrointestinal tract remains unknown. Since the medulla oblongata regulates the digestive function, it is plausible that the medulla oblongata is involved in the zymosan-induced inhibition of feed passage. The present study was performed to identify the genes that were affected by zymosan within the medulla oblongata of chicks (Gallus gallus) using an RNA sequencing approach. We found that mRNAs of several bioactive molecules including neuropeptide Y (NPY) were increased with an intraperitoneal (IP) injection of zymosan. The increase of mRNA expression of NPY in the medulla oblongata was also observed after the IP injection of lipopolysaccharide, derived from gram-negative bacteria. These results suggest that medullary NPY is associated with physiological changes during fungal and bacterial infection. Furthermore, we found that intracerebroventricular injection of NPY and its receptor agonists reduced the feed passage from the crop. Additionally, the injection of NPY reduced the feed passage from the proventriculus to lower digestive tract. NPY also suppressed the activity of duodenal activities of amylase and trypsin. The present study suggests that fungi- and bacteria-induced activation of the immune system may activate the NPY neurons in the medulla oblongata and thereby reduce the digestive function in chicks.