A commensal protozoan attenuates Clostridioides difficile pathogenesis in mice via arginine-ornithine metabolism and host intestinal immune response.

Antibiotic-induced dysbiosis is a major risk factor for Clostridioides difficile infection (CDI), and fecal microbiota transplantation (FMT) is recommended for treating CDI. However, the underlying mechanisms remain unclear. Here, we show that Tritrichomonas musculis (T.mu), an integral member of the mouse gut commensal microbiota, reduces CDI-induced intestinal damage by inhibiting neutrophil recruitment and IL-1ß secretion, while promoting Th1 cell differentiation and IFN-γ secretion, which in turn enhances goblet cell production and mucin secretion to protect the intestinal mucosa. T.mu can actively metabolize arginine, not only influencing the host's arginine-ornithine metabolic pathway, but also shaping the metabolic environment for the microbial community in the host's intestinal lumen. This leads to a relatively low ornithine state in the intestinal lumen in C. difficile-infected mice. These changes modulate C. difficile's virulence and the host intestinal immune response, and thus collectively alleviating CDI. These findings strongly suggest interactions between an intestinal commensal eukaryote, a pathogenic bacterium, and the host immune system via inter-related arginine-ornithine metabolism in the regulation of pathogenesis and provide further insights for treating CDI.

Bacterial accumulation in intestinal folds induced by physical and biological factors.

BACKGROUND: The gut microbiota, vital for host health, influences metabolism, immune function, and development. Understanding the dynamic processes of bacterial accumulation within the gut is crucial, as it is closely related to immune responses, antibiotic resistance, and colorectal cancer. We investigated Escherichia coli behavior and distribution in zebrafish larval intestines, focusing on the gut microenvironment. RESULTS: We discovered that E. coli spread was considerably suppressed within the intestinal folds, leading to a strong physical accumulation in the folds. Moreover, a higher concentration of E. coli on the dorsal side than on the ventral side was observed. Our in vitro microfluidic experiments and theoretical analysis revealed that the overall distribution of E. coli in the intestines was established by a combination of physical factor and bacterial taxis. CONCLUSIONS: Our findings provide valuable insight into how the intestinal microenvironment affects bacterial motility and accumulation, enhancing our understanding of the behavioral and ecological dynamics of the intestinal microbiota.

Advancements in understanding bacterial enteritis pathogenesis through organoids.

Bacterial enteritis has a substantial role in contributing to a large portion of the global disease burden and serves as a major cause of newborn mortality. Despite advancements gained from current animal and cell models in improving our understanding of pathogens, their widespread application is hindered by apparent drawbacks. Therefore, more precise models are imperatively required to develop more accurate studies on host-pathogen interactions and drug discovery. Since the emergence of intestinal organoids, massive studies utilizing organoids have been conducted to study the pathogenesis of bacterial enteritis, revealing new mechanisms and validating established ones. In this review, we focus on the advancements of several bacterial pathogenesis mechanisms observed in intestinal organoid/enteroid models, exploring the host response and bacterial effectors during the infection process. Finally, we address the features that warrant additional investigation or could be enhanced in existing organoid models in order to guide future research endeavors.

Potential contributions of keystone species to intestinal ecosystem in patients with Crohn's disease.

AIMS: Ravelling the central but poorly understood issue that potential contributions of keystone species to intestinal ecosystem functioning of patients with certain life-altering diseases including Crohn's disease (CD). METHODS AND RESULTS: In this study, a combination of 16S rRNA gene amplicon sequencing and amplicon-oriented metagenomic profiling was applied to gain insights into the shifts in bacterial community composition at different stages of CD course, and explore the functional roles of identified keystone species in intestinal microecosystem. Our results showed significant alterations in structure and composition of gut microbiota between CD patients and healthy control (HC) (P < 0.05), but was no difference at active and remission stages. Whole-community-based comprehensive analyses were employed to identify the differential species such as Escherichia coli, Anaerostipes hadrus, and Eubacterium hallii in CD patients, with healthy populations as the control. Metagenome-wide functional analyses further revealed that the relative abundance of specialized metabolism-related genes such as cynS, frdB, serA, and gltB from these bacterial species in CD group was significantly different (P < 0.05) from that in HC, and highlighted the potential roles of the keystone species in regulating the accumulation of important metabolites such as succinate, formate, ammonia, L-glutamate, and L-serine, which might have an effect on homeostasis of intestinal ecosystem. CONCLUSIONS: The findings identify several potential keystone species that may influence the intestinal microecosystem functioning of CD patients and provide some reference for future CD treatment.

[The role of intestinal alkaline phosphatase in the development of obesity. Modulation of enzyme activity by high fat diet and dietary fiber].

Interest to the tissue-specific intestinal isoenzyme of alkaline phosphatase (IAP) has increased in recent years due to eating disorders that have led to widespread obesity and diet-related diseases. Obesity is considered as an inflammation of low intensity, which is accompanied by the manifestation of various metabolic complications and a disturbance of intestinal homeostasis. IAP is one of the participants in the mechanism of the macroorganism protection against inflammatory and infectious processes, carrying out enzymatic detoxification of bacterial lipopolysaccharide (the trigger of the inflammatory process). Deficiency of IAP activity contributes to the risk of obesity, inflammatory diseases. The objective of the research was to summarize the current understanding of the role of IAP involved in the molecular mechanism of diet-induced obesity and to evaluate the impact of dietary components - fats and dietary fiber on IAP activity. Material and methods. A literature search on the role of IAP in the development of obesity was carried out using PubMed, Scopus, Web of Science, Google Scholar, ResearchGate, RSCI databases. Results. IAP prevents the development of the inflammatory process by participating in the detoxification of toxic bacterial products, limiting the translocation of pathogenic bacteria from the intestine to various tissues and organs of the macroorganism. The enzyme maintains the integrity of the intestinal barrier, influencing the synthesis and proper localization of tight junction's proteins between intestinal epithelial cells, promotes changes in the composition of the microbiota, decreasing pathogenic bacteria and increasing the population of the community of beneficial microorganisms. IAP is involved in the regulation of fatty acid absorption and influences on the adipogenesis. Monitoring the activity of IAP present in human stool can predict the early development of such complications associated with obesity as metabolic syndrome and diabetes mellitus, Some nutrients modulate IAP activity. Depending on the amount, type, composition of fats and the duration of their consumption, either an increase or decrease in the IAP activity are observed, while dietary fibers stimulate the activity of the enzyme. Conclusion. IAP activity can be considered as an early predictor of the risk of obesity. Deficiency of IAP activity contributes to the development of obesity caused by high-fat diet. The high activity of the enzyme contributes to the support of intestinal homeostasis and limits transepithelial movement of bacteria, weakening the inflammatory process induced by lipopolysaccharides, the excess concentration of which is detected in obesity. Stimulating enzyme activity through dietary intervention reduces the risk of obesity and metabolic complications.

Nitrite nitrogen stress disrupts the intestine bacterial community by altering host-community interactions in shrimp.

Environmental stress can disrupt the intricate interactions between the host and intestine microbiota, thereby impacting the host health. In this study, we aimed to elucidate the dynamic changes in the bacterial community within shrimp intestines under nitrite nitrogen (nitrite-N) stress and investigate potential host-related factors influencing these changes. Our results revealed a significant reduction in community diversity within the intestine exposed to nitrite-N compared to control conditions. Furthermore, distinct differences in community structures were observed between these two groups at 72 h and 120 h post-stress induction. Nitrite-N stress also altered the abundances of some bacterial species in the intestine dramatically. It is noteworthy that, in comparison to the 72 h, intestine bacterial community structure of stressed shrimp exhibited a significantly higher degree of dispersion after 120 h of nitrite-N stress when compared to control shrimp, and the relative abundance of numerous bacterial species experienced a substantial decrease or even reached 0 %. Moreover, it led to a reduction in bacterial community interactions and decreased competitiveness within the intestine microbiota. Notably, the influence of bacterial community assemblies in the shrimp intestine shifted from a stochastic process to a deterministic one after 24 h and 72 h of nitrite-N stress, returning to a stochastic process at 120 h. We further observed a close association between this phenomenon and host's response to nitrite-N stress. Expression levels of differentially expressed genes in the intestinal tissue significantly impact the intestine bacterial diversity and abundance of species. In particular, the significant decline in bacterial diversity and abundances of quite a few species in intestine was attributed to the up-regulation of peritrophin-48-like. Overall, nitrite-N stress indeed disrupted the intestine microbiota and changed the host-microbiota interactions of shrimp. This study offered novel insights into environment-host-microbiota interactions and also provided practical guidance for promoting healthy shrimp cultivation practices.

A distinct Fusobacterium nucleatum clade dominates the colorectal cancer niche.

Fusobacterium nucleatum (Fn), a bacterium present in the human oral cavity and rarely found in the lower gastrointestinal tract of healthy individuals1, is enriched in human colorectal cancer (CRC) tumours2-5. High intratumoural Fn loads are associated with recurrence, metastases and poorer patient prognosis5-8. Here, to delineate Fn genetic factors facilitating tumour colonization, we generated closed genomes for 135 Fn strains; 80 oral strains from individuals without cancer and 55 unique cancer strains cultured from tumours from 51 patients with CRC. Pangenomic analyses identified 483 CRC-enriched genetic factors. Tumour-isolated strains predominantly belong to Fn subspecies animalis (Fna). However, genomic analyses reveal that Fna, considered a single subspecies, is instead composed of two distinct clades (Fna C1 and Fna C2). Of these, only Fna C2 dominates the CRC tumour niche. Inter-Fna analyses identified 195 Fna C2-associated genetic factors consistent with increased metabolic potential and colonization of the gastrointestinal tract. In support of this, Fna C2-treated mice had an increased number of intestinal adenomas and altered metabolites. Microbiome analysis of human tumour tissue from 116 patients with CRC demonstrated Fna C2 enrichment. Comparison of 62 paired specimens showed that only Fna C2 is tumour enriched compared to normal adjacent tissue. This was further supported by metagenomic analysis of stool samples from 627 patients with CRC and 619 healthy individuals. Collectively, our results identify the Fna clade bifurcation, show that specifically Fna C2 drives the reported Fn enrichment in human CRC and reveal the genetic underpinnings of pathoadaptation of Fna C2 to the CRC niche.

Development of Orally Ingestible IgA Antibody Drugs to Maintain Symbiosis Between Humans and Microorganisms.

In recent years, dysbiosis, abnormalities in the gut microbiota, has been reported to be associated with the development of many diseases, and improving the gut microbiota is important for health maintenance. It has been shown that the host recognizes and regulates intestinal bacteria by means of IgA antibodies secreted into the gut, but the precise nature of the commensal gut bacteria recognized by each IgA antibody is unclear. We have cloned monoclonal IgA antibodies from mouse intestinal IgA-producing cells and are searching for bacterial molecules recognized by each IgA clone. Although the interaction of IgA antibodies with intestinal bacteria is still largely unknown and requires further basic research, we discuss the potential use of orally ingestible IgA antibodies as agents to improve intestinal microbiota.

The hyphal-specific toxin candidalysin promotes fungal gut commensalism.

The fungus Candida albicans frequently colonizes the human gastrointestinal tract, from which it can disseminate to cause systemic disease. This polymorphic species can transition between growing as single-celled yeast and as multicellular hyphae to adapt to its environment. The current dogma of C. albicans commensalism is that the yeast form is optimal for gut colonization, whereas hyphal cells are detrimental to colonization but critical for virulence1-3. Here, we reveal that this paradigm does not apply to multi-kingdom communities in which a complex interplay between fungal morphology and bacteria dictates C. albicans fitness. Thus, whereas yeast-locked cells outcompete wild-type cells when gut bacteria are absent or depleted by antibiotics, hyphae-competent wild-type cells outcompete yeast-locked cells in hosts with replete bacterial populations. This increased fitness of wild-type cells involves the production of hyphal-specific factors including the toxin candidalysin4,5, which promotes the establishment of colonization. At later time points, adaptive immunity is engaged, and intestinal immunoglobulin A preferentially selects against hyphal cells1,6. Hyphal morphotypes are thus under both positive and negative selective pressures in the gut. Our study further shows that candidalysin has a direct inhibitory effect on bacterial species, including limiting their metabolic output. We therefore propose that C. albicans has evolved hyphal-specific factors, including candidalysin, to better compete with bacterial species in the intestinal niche.

Bacillus halotolerans SW207 alleviates enterotoxigenic Escherichia coli-induced inflammatory responses in weaned piglets by modulating the intestinal epithelial barrier, the TLR4/MyD88/NF-κB pathway, and intestinal microbiota.

Enterotoxigenic Escherichia coli (ETEC) is one of the major pathogens contributing to piglet diarrhea, with significant implications for both piglet health and the economic aspects of the livestock industry. SW207 is an isolate of Bacillus halotolerans isolated from the cold- and disease-resistant Leixiang pigs in Northeastern China. We have discovered that SW207 can survive in the pig's gastrointestinal fluid and under conditions of high bile salt concentration, displaying potent antagonistic activity against ETEC. In this study, we established a weaned piglet diarrhea model infected with ETEC to investigate the role of SW207 in preventing diarrhea and improving intestinal health. Results indicate that SW207 upregulates the expression of tight junction proteins, including claudin-1, occludin, and zonula occludens-1, at both the transcriptional and translational levels. Furthermore, SW207 reduces serum endotoxin, D-lactic acid, and various oxidative stress markers while enhancing piglet mechanical barrier function. In terms of immune barrier, SW207 suppressed the activation of the TLR4/MyD88/NF-κB pathway, reducing the expression of various inflammatory factors and upregulating the expression of small intestine mucosal sIgA. Concerning the biological barrier, SW207 significantly reduces the content of E. coli in the intestines and promotes the abundance of beneficial bacteria, thereby mitigating the microbiota imbalance caused by ETEC. In summary, SW207 has the potential to prevent weaned piglet diarrhea caused by ETEC, alleviate intestinal inflammation and epithelial damage, and facilitate potential beneficial changes in the intestinal microbiota. This contributes to elucidating the potential mechanisms of host-microbe interactions in preventing pathogen infections.IMPORTANCEEnterotoxigenic Escherichia coli (ETEC) has consistently been one of the significant pathogens causing mortality in weaned piglets in pig farming. The industry has traditionally relied on antibiotic administration to control ETEC-induced diarrhea. However, the overuse of antibiotics has led to the emergence of drug-resistant zoonotic bacterial pathogens, posing a threat to public health. Therefore, there is an urgent need to identify alternatives to control pathogens and reduce antibiotic usage. In this study, we assessed the protective effect of a novel probiotic in a weaned piglet model infected with ETEC and analyzed its mechanisms both in vivo and in vitro. The study results provide theoretical support and reference for implementing interventions in the gut microbiota to alleviate early weaned piglet diarrhea and improve intestinal health.

Interactions between Gut Microbiota and Oral Antihyperglycemic Drugs: A Systematic Review.

The intestinal microbiota refers to the collection of microorganisms that exist in the human gut. It has been said that bacteria influence the development of metabolic diseases, such as diabetes mellitus, as they have roles in immunomodulation, protection against pathogens, blood vessel growth, repairing the intestinal wall, and the development of the neurological system. In this review, we look at the latest research regarding interactions between gut microbiota and oral antihyperglycemic drugs and we present data suggesting that the microbiome may help counteract the reduced glucose tolerance and insulin resistance associated with metabolic disorders. We found that antidiabetic drugs can have significant impacts on gut microbiota composition and function, potentially influencing both the efficacy and side effects of these medications. Additionally, we discovered that microbial-based therapeutics, including probiotics, prebiotics, and postbiotics, and fecal microbiota can be considered when discussing preventive measures and personalized treatment options for type 2 diabetes mellitus. Understanding how antidiabetic drugs modulate gut microbiota composition and function is essential for optimizing their therapeutic efficacy and minimizing potential adverse effects. The relationship between the gut microbiota and glycemic agents, not fully understood, is currently the subject of increasing research and discussion. It has been proven that the microbiome can impact the effectiveness of the medications, but further research in this field may uncover novel therapeutic strategies for diabetes and other metabolic disorders by targeting the gut microbiota.

Distinct intestinal microbial signatures linked to accelerated systemic and intestinal biological aging.

BACKGROUND: People living with HIV (PLWH), even when viral replication is controlled through antiretroviral therapy (ART), experience persistent inflammation. This inflammation is partly attributed to intestinal microbial dysbiosis and translocation, which may lead to non-AIDS-related aging-associated comorbidities. The extent to which living with HIV - influenced by the infection itself, ART usage, sexual orientation, or other associated factors - affects the biological age of the intestines is unclear. Furthermore, the role of microbial dysbiosis and translocation in the biological aging of PLWH remains to be elucidated. To investigate these uncertainties, we used a systems biology approach, analyzing colon and ileal biopsies, blood samples, and stool specimens from PLWH on ART and people living without HIV (PLWoH) as controls. RESULTS: PLWH exhibit accelerated biological aging in the colon, ileum, and blood, as measured by various epigenetic aging clocks, compared to PLWoH. Investigating the relationship between microbial translocation and biological aging, PLWH had decreased levels of tight junction proteins in the intestines, along with increased microbial translocation. This intestinal permeability correlated with faster biological aging and increased inflammation. When investigating the relationship between microbial dysbiosis and biological aging, the intestines of PLWH had higher abundance of specific pro-inflammatory bacteria, such as Catenibacterium and Prevotella. These bacteria correlated with accelerated biological aging. Conversely, the intestines of PLWH had lower abundance of bacteria known for producing the anti-inflammatory short-chain fatty acids, such as Subdoligranulum and Erysipelotrichaceae, and these bacteria were associated with slower biological aging. Correlation networks revealed significant links between specific microbial genera in the colon and ileum (but not in feces), increased aging, a rise in pro-inflammatory microbe-related metabolites (e.g., those in the tryptophan metabolism pathway), and a decrease in anti-inflammatory metabolites like hippuric acid. CONCLUSIONS: We identified specific microbial compositions and microbiota-related metabolic pathways that are intertwined with intestinal and systemic biological aging. This microbial signature of biological aging is likely reflecting various factors including the HIV infection itself, ART usage, sexual orientation, and other aspects associated with living with HIV. A deeper understanding of the mechanisms underlying these connections could offer potential strategies to mitigate accelerated aging and its associated health complications. Video Abstract.

Intestinal lysozyme1 deficiency alters microbiota composition and impacts host metabolism through the emergence of NAD+-secreting ASTB Qing110 bacteria.

The intestine plays a pivotal role in nutrient absorption and host defense against pathogens, orchestrated in part by antimicrobial peptides secreted by Paneth cells. Among these peptides, lysozyme has multifaceted functions beyond its bactericidal activity. Here, we uncover the intricate relationship between intestinal lysozyme, the gut microbiota, and host metabolism. Lysozyme deficiency in mice led to altered body weight, energy expenditure, and substrate utilization, particularly on a high-fat diet. Interestingly, these metabolic benefits were linked to changes in the gut microbiota composition. Cohousing experiments revealed that the metabolic effects of lysozyme deficiency were microbiota-dependent. 16S rDNA sequencing highlighted differences in microbial communities, with ASTB_g (OTU60) highly enriched in lysozyme knockout mice. Subsequently, a novel bacterium, ASTB Qing110, corresponding to ASTB_g (OTU60), was isolated. Metabolomic analysis revealed that ASTB Qing110 secreted high levels of NAD+, potentially influencing host metabolism. This study sheds light on the complex interplay between intestinal lysozyme, the gut microbiota, and host metabolism, uncovering the potential role of ASTB Qing110 as a key player in modulating metabolic outcomes. IMPORTANCE: The impact of intestinal lumen lysozyme on intestinal health is complex, arising from its multifaceted interactions with the gut microbiota. Lysozyme can both mitigate and worsen certain health conditions, varying with different scenarios. This underscores the necessity of identifying the specific bacterial responses elicited by lysozyme and understanding their molecular foundations. Our research reveals that a deficiency in intestinal lysozyme1 may offer protection against diet-induced obesity by altering bacterial populations. We discovered a strain of bacterium, ASTB Qing110, which secretes NAD+ and is predominantly found in lyz1-deficient mice. Qing110 demonstrates positive effects in both C. elegans and mouse models of ataxia telangiectasia. This study sheds light on the intricate role of lysozyme in influencing intestinal health.

Distribution and roles of Ligilactobacillus murinus in hosts.

Ligilactobacillus murinus, a member of the Ligilactobacillus genus, holds significant potential as a probiotic. While research on Ligilactobacillus murinus has been relatively limited compared to well-studied probiotic lactic acid bacteria such as Limosilactobacillus reuteri and Lactobacillus gasseri, a mounting body of evidence highlights its extensive involvement in host intestinal metabolism and immune activities. Moreover, its abundance exhibits a close correlation with intestinal health. Notably, beyond the intestinal context, Ligilactobacillus murinus is gaining recognition for its contributions to metabolism and regulation in the oral cavity, lungs, and vagina. As such, Ligilactobacillus murinus emerges as a potential probiotic candidate with a pivotal role in supporting host well-being. This review delves into studies elucidating the multifaceted roles of Ligilactobacillus murinus. It also examines its medicinal potential and associated challenges, underscoring the imperative to delve deeper into unraveling the mechanisms of its actions and exploring its health applications.

The reproductive microbiome and maternal transmission of microbiota via eggs in Sceloporus virgatus.

Maternal transmission of microbes occurs across the animal kingdom and is vital for offspring development and long-term health. The mechanisms of this transfer are most well-studied in humans and other mammals but are less well-understood in egg-laying animals, especially those with no parental care. Here, we investigate the transfer of maternal microbes in the oviparous phrynosomatid lizard, Sceloporus virgatus. We compared the microbiota of three maternal tissues-oviduct, cloaca, and intestine-to three offspring sample types: egg contents and eggshells on the day of oviposition, and hatchling intestinal tissue on the day of hatching. We found that maternal identity is an important factor in hatchling microbiome composition, indicating that maternal transmission is occurring. The maternal cloacal and oviductal communities contribute to offspring microbiota in all three sample types, with minimal microbes sourced from maternal intestines. This indicates that the maternal reproductive microbiome is more important for microbial inheritance than the gut microbiome, and the tissue-level variation of the adult S. virgatus microbiota must develop as the hatchling matures. Despite differences between adult and hatchling communities, offspring microbiota were primarily members of the Enterobacteriaceae and Yersiniaceae families (Phylum Proteobacteria), consistent with this and past studies of adult S. virgatus microbiomes.

High-fat diet disrupts the gut microbiome, leading to inflammation, damage to tight junctions, and apoptosis and necrosis in Nyctereutes procyonoides intestines.

Given the burgeoning Nyctereutes procyonoides breeding industry and its growing scale, it is imperative to investigate the impact of high-fat diets on the health of these animals. This study involved 30 male Nyctereutes procyonoides of comparable weights (3 kg ±0.5), randomly assigned to either a control group or a high-fat diet group (n = 15 each). The latter group was fed a mixture of lard and basal diet in a 2:5 ratio, establishing a high-fat diet model in Nyctereutes procyonoides. This diet induced diarrhea and histopathological changes in the Nyctereutes procyonoides. Analysis of the small intestine contents using 16S rRNA sequencing revealed a high-fat diet-induced disruption in the gut microbiota. Specifically, Escherichia-Shigella emerged as the biomarker in the high-fat diet group (P = 0.049), while Vagococcus was prevalent in the control group (P = 0.049), indicating a significant increase in harmful bacteria in the high-fat diet group. Furthermore, this disrupted gut flora correlated with inflammation and oxidative stress, as evidenced by marked increases in TNF-α (P < 0.01), IL-1ß (P < 0.05), and IL-6 (P < 0.05) levels, measured via q-PCR, Western blot, and oxidative stress assays. In addition, q-PCR analysis revealed significant upregulation of apoptosis and necrosis markers, including Bax, Caspase3, Caspase9, Caspase12, RIPK3, and RIPK1 (P < 0.01 to P < 0.001), and a concurrent downregulation of the anti-apoptotic gene Bcl-2 (P < 0.01) in the high-fat diet group, consistent with protein expression trends. These findings suggest that a high-fat diet alters the gut microbiome toward a more harmful bacterial composition, escalating inflammatory responses and intestinal tissue permeability, culminating in intestinal cell apoptosis and necrosis.IMPORTANCEThis study examines the impact of high-fat diets on Nyctereutes procyonoides. Our research established a Nyctereutes procyonoides model on a high-fat diet, revealing significant health impacts, such as diarrhea, histological anomalies, and alterations in the gut microbiota. These findings emphasize the importance of preventing health issues and promoting sustainable industry growth. They highlight the significant impact of diet on gut microbiota and overall animal health.

Citric Acid Promotes Immune Function by Modulating the Intestinal Barrier.

Amidst increasing concern about antibiotic resistance resulting from the overuse of antibiotics, there is a growing interest in exploring alternative agents. One such agent is citric acid, an organic compound commonly used for various applications. Our research findings indicate that the inclusion of citric acid can have several beneficial effects on the tight junctions found in the mouse intestine. Firstly, the study suggests that citric acid may contribute to weight gain by stimulating the growth of intestinal epithelial cells (IE-6). Citric acid enhances the small intestinal villus-crypt ratio in mice, thereby promoting intestinal structural morphology. Additionally, citric acid has been found to increase the population of beneficial intestinal microorganisms, including Bifidobacterium and Lactobacillus. It also promotes the expression of important protein genes such as occludin, ZO-1, and claudin-1, which play crucial roles in maintaining the integrity of the tight junction barrier in the intestines. Furthermore, in infected IEC-6 cells with H9N2 avian influenza virus, citric acid augmented the expression of genes closely associated with the influenza virus infection. Moreover, it reduces the inflammatory response caused by the viral infection and thwarted influenza virus replication. These findings suggest that citric acid fortifies the intestinal tight junction barrier, inhibits the replication of influenza viruses targeting the intestinal tract, and boosts intestinal immune function.

Genetic mutation in Escherichia coli genome during adaptation to the murine intestine is optimized for the host diet.

Mammalian gut microbes colonize the intestinal tract of their host and adapt to establish a microbial ecosystem. The host diet changes the nutrient profile of the intestine and has a high impact on microbiota composition. Genetic mutations in Escherichia coli, a prevalent species in the human gut, allow for adaptation to the mammalian intestine, as reported in previous studies. However, the extent of colonization fitness in the intestine elevated by genetic mutation and the effects of diet change on these mutations in E. coli are still poorly known. Here, we show that notable mutations in sugar metabolism-related genes (gatC, araC, and malI) were detected in the E. coli K-12 genome just 2 weeks after colonization in the germ-free mouse intestine. In addition to elevated fitness by deletion of gatC, as previously reported, deletion of araC and malI also elevated E. coli fitness in the murine intestine in a host diet-dependent manner. In vitro cultures of medium containing nutrients abundant in the intestine (e.g., galactose, N-acetylglucosamine, and asparagine) also showed increased E. coli fitness after deletion of the genes-of-interest associated with their metabolism. Furthermore, the host diet was found to influence the developmental trajectory of gene mutations in E. coli. Taken together, we suggest that genetic mutations in E. coli are selected in response to the intestinal environment, which facilitates efficient utilization of nutrients abundant in the intestine under laboratory conditions. Our study offers some insight into the possible adaptation mechanisms of gut microbes.IMPORTANCEThe gut microbiota is closely associated with human health and is greatly impacted by the host diet. Bacteria such as Escherichia coli live in the gut all throughout the life of a human host and adapt to the intestinal environment. Adaptive mutations in E. coli are reported to enhance fitness in the mammalian intestine, but to what extent is still poorly known. It is also unknown whether the host diet affects what genes are mutated and to what extent fitness is affected. This study suggests that genetic mutations in the E. coli K-12 strain are selected in response to the intestinal environment and facilitate efficient utilization of abundant nutrients in the germ-free mouse intestine. Our study provides a better understanding of these intestinal adaptation mechanisms of gut microbes.

Impaired intestinal immunity and microbial diversity in common carp exposed to cadmium.

Waterborne cadmium (Cd) accumulates in the fish intestine and causes irreversible toxicity by disrupting intestinal immunity and microbial diversity. To explore the toxicity of environmentally available high Cd concentration on intestinal immunity and microbial diversity of fish, we selected the widely used bioindicator model species, Common carp (Cyprinus carpio). Literature review and Cd pollution data supported sequential doses of 0.2, 0.4, 0.8, 1.6, 3.2, and 6.4 mg/L Cd for 30 days. Based on intestinal tissue Cd accumulation, previous studies, and environmentally available Cd data, 0.4 and 1.6 mg/L Cd were selected for further studies. Intestinal Cd bioaccumulation increased significantly to ~100 times in fish exposed to 1.6 mg/L Cd. We observed villous atrophy, increased goblet cells with mucus production, muscularis erosion, and thickened lamina propria due to intense inflammatory cell infiltration in the intestine at this Cd concentration. Cd-induced immunosuppression occurred with increased lysozyme, alkaline phosphate (AKP), and acid phosphate (ACP). High levels of catalase (CAT), total antioxidant capacity (T-AOC), malondialdehyde (MDA), and hydrogen peroxide (H2O2) suggested induced oxidative stress and poor metabolism by α-amylase and lipase suppression for Cd toxicity. Proteobacteria (41.2 %), Firmicutes (21.8 %), and Bacteroidetes (17.5 %) were the dominant bacterial phyla in the common carp intestine. Additionally, potential pathogenic Cyanobacteria increased in Cd-treated fish. The decrease of beneficiary bacteria like Aeromonas, and Cetobacterium indicated Cd toxicity. Overall, these findings indicate harmful consequences of high Cd concentration in the intestinal homeostasis and health status of fish.

Postbiotics: An alternative and innovative intervention for the therapy of inflammatory bowel disease.

Inflammatory Bowel Disease (IBD) is a persistent gastrointestinal (GI) tract inflammatory disease characterized by downregulated mucosal immune activities and a disrupted microbiota environment in the intestinal lumen. The involvement of bacterium postbiotics as mediators between the immune system and gut microbiome could be critical in determining why host-microbial relationships are disrupted in IBD. Postbiotics including Short-chain fatty acids (SCFAs), Organic acids, Proteins, Vitamins, Bacteriocins, and Tryptophan (Trp) are beneficial bioactive compounds formed via commensal microbiota in the gut environment during the fermentation process that can be used to improve consumer health. The use of metabolites or fragments from microorganisms can be a very attractive treatment and prevention technique in modern medicine. Postbiotics are essential in the immune system's development since they alter the barrier tightness, and the gut ecology and indirectly shape the microbiota's structure. As a result, postbiotics may be beneficial in treating or preventing various diseases, even some for which there is no effective causative medication. Postbiotics may be a promising tool for the treatment of IBD in individuals of all ages, genders, and even geographical locations. Direct distribution of postbiotics may provide a new frontier in microbiome-based therapy for IBD since it allows both the management of host homeostasis and the correction of the negative implications of dysbiosis. Further studies of the biological effects of these metabolites are expected to reveal innovative applications in medicine and beyond. This review attempts to explore the possible postbiotic-based interventions for the treatment of IBD.