Immune checkpoint inhibitors (ICIs) constitute a major breakthrough in the field of cancer therapy; their use has resulted in improved outcomes across various tumour types. However, ICIs can cause a diverse range of immune-related adverse events (irAEs) that present a considerable challenge to the efficacy and safety of these treatments. The gut microbiota has been demonstrated to have a crucial role in modulating the tumour immune microenvironment and thus influences the effectiveness of ICIs. Accumulating evidence indicates that alterations in the composition and function of the gut microbiota are also associated with an increased risk of irAEs, particularly ICI-induced colitis. Indeed, these changes in the gut microbiota can contribute to the pathogenesis of irAEs. In this Review, we first summarize the current clinical challenges posed by irAEs. We then focus on reported correlations between alterations in the gut microbiota and irAEs, especially ICI-induced colitis, and postulate mechanisms by which these microbial changes influence the occurrence of irAEs. Finally, we highlight the potential value of gut microbial changes as biomarkers for predicting irAEs and discuss gut microbial interventions that might serve as new strategies for the management of irAEs, including faecal microbiota transplantation, probiotic, prebiotic and/or postbiotic supplements, and dietary modulations.

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a rare neurodevelopmental disorder often associated with gastrointestinal (GI) issues and subclinical immune dysregulation, suggesting a link to the gut microbiota. We analyze the fecal microbiota composition in two CDKL5 knockout (KO) mouse models at postnatal days (P) 25, 32 (youth), and 70 (adulthood), revealing significant microbial imbalances, particularly during juvenile stages. To investigate the role of the intestinal microbiota in CDD and assess causality, we administer antibiotics, which lead to improved visual cortical responses and reduce hyperactivity. Additionally, microglia morphology changes, indicative of altered surveillance and activation states, are reversed. Strikingly, fecal transplantation from CDKL5 KO to wild-type (WT) recipient mice successfully transfers both visual response deficits and hyperactive behavior. These findings show that gut microbiota alterations contribute to the severity of neurological symptoms in CDD, shedding light on the interplay between microbiota, microglia, and neurodevelopmental outcomes.

Tumor necrosis factor (TNF) is a pleiotropic cytokine that plays a critical role in the pathogenesis of immune-mediated diseases including inflammatory bowel disease (IBD). The stability of its mRNA transcript, determined in part by destabilizing sequences in its AAUU repeats (ARE) gene region, is an important regulator of its tissue and systemic levels. A deletion in the ARE region of the gene resulted in IBD and arthritis in mice and pigs, supporting a critical role for the cytokine in human IBD and several human arthritides. A mutation in the same area of the mouse genome by Genentech scientists (T.Y., M.K.) resulted in a similar but not identical phenotype.

Here, we compare histopathological, cellular, and molecular features of the strains and propose reasons for their distinct phenotypes. First, while homozygous TNFΔARE mice develop severe arthritis and die after weaning, homozygous Genentech TNFΔARE (ΔG/ΔG) mice have normal lifespans, and males are often fertile.

We found that while the ileitic phenotype had peaked at 12 weeks of age in all mice, colitis progressed mostly after 20 weeks of age in heterozygous mice. Their variably penetrant arthritic phenotype progressed mostly after 20 weeks, also in heterozygous mice from both strains. There was expansion of central memory T and B cells in lymphoid organs of TNF-overproducing strains and their transcriptional profile shared well-known pathogenetic pathways with human IBD. Finally, we found differences in the mutated sequences within the ARE regions of the TNF gene and in their microbiota composition and genetic background. These differences likely explain their phenotypic differences.

In summary, we describe a different strain of TNF-overproducing mice with an overlapping, yet not identical phenotype, which may have differential applications than the original strain.

The fermentation products of soybean are rich in beneficial bacteria, which play Shenghui Chu a significant role in maintaining the balance of intestinal microbiota and improving intestinal health. To investigate the immunomodulatory effects of soybean fermentation broth (S-FB) on loach (Misgurnus anguillicaudatus) with lipopolysaccharide (LPS)-induced enteritis, 16S rDNA high-throughput sequencing technology was employed to analyze the composition and structure of intestinal microbiota in two groups: the LPS-treated group (fed with soybean broth) and the control group (normal feeding conditions). The results revealed that the relative abundance of beneficial bacteria, such as Lactobacillus and Muribaculaceae, significantly increased in the treatment group, while the relative abundance of harmful bacteria, including Aeromonas and Shewanella, decreased. These findings suggest that soybean fermentation broth can repair intestinal damage and maintain intestinal health by enhancing the abundance of beneficial bacteria and reducing the pathogenic effects of harmful bacteria on the host. Functional prediction studies of microbial communities also showed that treatment groups primarily affected metabolic and genetic information processing. The research results analyzed the changes in the structure and distribution of intestinal microflora in different groups of loach, providing new insights into the possible role of soybean fermentation liquid in intestinal inflammation.

Fermentation of Astragalus by Lactobacillus plantarum and Bacillus coagulans can increase the release of active components and degrade its macromolecular substances. This study investigated the effect of fermentation products (Astragalus + L. plantarum + B. coagulans, ALB) on largemouth bass. We specifically focused on growth performance, serum biochemical indices, intestinal microbial diversity, intestinal enzyme activity, immune gene expression and resistance to infections by Aeromonas hydrophila and largemouth bass ranavirus (LMBRaV). The largemouth bass were divided into five groups based on the amount of ALB added to the feed as following, (1) ALB0 (no ALB, ALB0.5 [0.5% addition of ALB], ALB1 [1% addition of ALB], ALB3 [3% addition of ALB], ALB5 [5% addition of ALB]). The feeding trial spanned 28 days. Comprehensively comparing the feeding results of different ALB concentration, the ALB0.5 group showed the best effect. The ALB0.5 group had significantly increased weight gain rate, alkaline phosphatase, total protein, albumin, digestive enzymes activities of lipase, trypsin and increased intestinal villi and thickness of muscularis propria. And it decreased feed conversion ratio, aspartate aminotransferase and alanine aminotransferase of largemouth bass. Furthermore, the ALB0.5 group improved the richness and diversity of the intestinal microbiota. Increased abundance of dominant phylum and genus in the intestine of largemouth bass included Fusobacteria and Cetobacterium, which promoted the growth and immune performance of largemouth bass. After infection with A. hydrophila and LMBRaV, the survival rates were higher in ALB addition experimental groups than in the ALB0 group, respectively. And the survival rate of ALB0.5 group was higher than other groups. Meanwhile, the ALB added to the feed could regulated the immune gene expression (Mx, IRF-3, TNF-α, IL-1β and IL-10), which also promoted the largemouth bass resistance to disease. In summary, adding 0.5% ALB to the diet of largemouth bass can boost its growth performance, immune genes expression, intestinal health and disease resistance.

Avian influenza virus (AIV) poses significant threats to poultry and human health. This study investigates the impact of H9N2 AIV infection on the respiratory microbiota of chickens using 16S rRNA gene sequencing. Total 48 one-day-old specific pathogen-free chickens were assigned to six groups: a control and five post-infection groups (days 1, 3, 5, 7, and 9). After a 15-day microbiota stabilization period, the infected chickens received a viral inoculum (107 TCID50/ml) via ocular, intra-nasal, and intra-tracheal routes. Tracheal and broncho-alveolar lavage samples were analyzed. Significant reductions in microbiota diversity were observed on days 5, 7, and 9 post-infection, compared to d0 controls. Permutational Multivariate Analysis of Variance confirmed significant beta diversity differences (P = 0.001) between infected and uninfected groups. The microbial shifts from d5 to d9 were marked by increased Proteobacteria, decreased Actinobacteria and Firmicutes, and a rise in Dickeya. Elevated type-I interferon (IFN-β) and viperin gene expression at d5 coincided with reduced microbiota diversity, highlighting the respiratory microbiota's role in modulating host responses to AIV H9N2 infection and suggesting potential biomarkers for respiratory dysbiosis.

Drug-induced dysbiosis, particularly from antibiotics, has emerged as a significant contributor to chronic diseases by disrupting gut microbiota composition and function. Plant-derived secondary metabolites, such as polysaccharides, polyphenols, alkaloids, and saponins, show potential in mitigating antibiotic-induced dysbiosis. This review aims to consolidate evidence from preclinical studies on the therapeutic effects of secondary metabolites in restoring gut microbial balance, emphasizing their mechanisms and efficacy.

A narrative review was conducted using PubMed, Scopus, and Web of Science. Studies were selected based on specific inclusion criteria, focusing on animal models treated with secondary metabolites for antibiotic-induced dysbiosis. The search terms included "gut microbiota", "antibiotics", and "secondary metabolites". Data extraction focused on microbial alterations, metabolite-specific effects, and mechanisms of action. Relevant findings were systematically analyzed and summarized.

Secondary metabolites demonstrated diverse effects in mitigating the impact of dysbiosis by modulating gut microbial composition, reducing inflammation, and supporting host biological markers. Polysaccharides and polyphenols restored the Firmicutes/Bacteroidetes ratio, increased beneficial taxa such as Lactobacillus and Bifidobacterium, and suppressed pathogenic bacteria like Escherichia-Shigella. Metabolites such as triterpenoid saponins enhanced gut barrier integrity by upregulating tight junction proteins, while alkaloids reduced inflammation by modulating proinflammatory cytokines (e.g., TNF-α, IL-1β). These metabolites also improved short-chain fatty acid production, which is crucial for gut and systemic health. While antibiotic-induced dysbiosis was the primary focus, other drug classes (e.g., PPIs, metformin) require further investigation.

Plant-derived secondary metabolites show promise in managing antibiotic-induced dysbiosis by restoring microbial balance, reducing inflammation, and improving gut barrier function. Future research should explore their applicability to other types of drug-induced dysbiosis and validate findings in human studies to enhance clinical relevance.

The toxigenic Klebsiella oxytoca strains secrete tilymicin and tilivalline enterotoxins, which cause antibiotic-associated hemorrhagic colitis. Both enterotoxins are non-ribosomal peptides synthesized by enzymes encoded in two divergent operons clustered in a pathogenicity island. The transcriptional regulator Lrp (leucine-responsive regulatory protein) controls the expression of several bacterial genes involved in virulence. In this work, we have uncovered novel findings that have significant implications. We determined the transcriptional expression of aroX and npsA, the first genes of each tilimycin (TM)/tilivalline (TV) biosynthetic operon in K. oxytoca MIT 09-7231 wild-type and its derivatives Δlrp mutant and complemented strains. Our results suggest that Lrp directly activates the transcription of both aroX and npsA genes by binding to the intergenic regulatory region in a leucine-dependent manner. Furthermore, the lack of Lrp significantly diminished the cytotoxicity of K. oxytoca on HeLa cells due to reduced production of TM and TV. Altogether, our data present a new perspective on the role of Lrp as a regulator in cytotoxin-producing K. oxytoca strains and how it controls the expression of genes involved in the biosynthesis of their main virulence factors.IMPORTANCETilimycin (TM) and tilivalline (TV) are enterotoxins that are a hallmark for the cytotoxin-producing Klebsiella oxytoca strains, which cause antibiotic-associated hemorrhagic colitis. The biosynthesis of TM and TV is driven by enzymes encoded by the aroX- and NRPS-operons. In this study, we discovered that the transcriptional regulator Lrp plays a crucial role in activating the expression of the aroX- and NRPS-operons, thereby initiating TM and TV biosynthesis. Our results underscore a molecular mechanism by which TM and TV production by toxigenic K. oxytoca strains is regulated and shed further light on developing strategies to prevent the intestinal illness caused by this enteric pathogen.

The bacteria living in the human gut are essential for host health. Though the composition and metabolism of these bacteria are well described in both healthy hosts and those with intestinal disease, less is known about the metabolic activity of the gut bacteria prior to, and during, disease development-especially regarding gut bacterial replication. Here, we use a recently developed single-cell technique alongside existing metagenomics-based tools to identify, track, and quantify replicating gut bacteria both ex vivo and in situ in the dextran sodium sulfate (DSS) mouse model of colitis. We show that the proportion of replicating gut bacteria decreases when mice have the highest levels of inflammation and returns to baseline levels as mice begin recovering. In addition, we report significant alterations in the composition of the replicating gut bacterial community ex vivo during colitis development. On the taxa level, we observe significant changes in the abundance of taxa such as the mucus-degrading Akkermansia and the poorly described Erysipelatoclostridium genus. We further demonstrate that many taxa exhibit variable replication rates in situ during colitis, including Akkermansia muciniphila. Lastly, we show that colitis development is positively correlated with increases in the presence and abundance of bacteria in situ which are predicted to be fast replicators. This could suggest that taxa with the potential to replicate quickly may have an advantage during intestinal inflammation. These data support the need for additional research using activity-based approaches to further characterize the gut bacterial response to intestinal inflammation and its consequences for both the host and the gut microbial community.IMPORTANCEIt is well known that the bacteria living inside the gut are important for human health. Indeed, the type of bacteria that are present and their metabolism are different in healthy people versus those with intestinal disease. However, less is known about how these gut bacteria are replicating, especially as someone begins to develop intestinal disease. This is particularly important as it is thought that metabolically active gut bacteria may be more relevant to health. Here, we begin to address this gap using several complementary approaches to characterize the replicating gut bacteria in a mouse model of intestinal inflammation. We reveal which gut bacteria are replicating, and how quickly, as mice develop and recover from inflammation. This work can serve as a model for future research to identify how actively growing gut bacteria may be impacting health, or why these particular bacteria tend to thrive during intestinal inflammation.

The term "gut microbiota" primarily refers to the ecological community of various microorganisms in the gut, which constitutes the largest microbial community in the human body. Although adequate bowel preparation can improve the results of colonoscopy, it may interfere with the gut microbiota. Bowel preparation for colonoscopy can lead to transient changes in the gut microbiota, potentially affecting an individual's health, especially in vulnerable populations, such as patients with inflammatory bowel disease. However, measures such as oral probiotics may ameliorate these adverse effects. We focused on the bowel preparation-induced changes in the gut microbiota and host health status, hypothesized the factors influencing these changes, and attempted to identify measures that may reduce dysbiosis, thereby providing more information for individualized bowel preparation for colonoscopy in the future.

The presence of skin flora (SF) has been identified as a significant factor in the onset and progression of cutaneous melanoma (CM). However, the vast diversity and abundance of SF present challenges to fully understanding the causal relationship between SF and CM.

A Two Sample Mendelian Randomization (TSMR) analysis was conducted to investigating the causal relationship between SF and CM. The Inverse-Variance Weighted (IVW) method was utilized as the primary approach to assess the causal relationship under investigation. Furthermore, an independent external cohort was employed to validate the initial findings, followed by a meta-analysis of the consolidated results. To address potential confounding factors related to the influence of SF on CM, a Multivariate Mendelian Randomization (MVMR) analysis was also conducted. Finally, a Reverse Mendelian Randomization (RMR) was conducted to further validate the causal association.

TSMR results showed that 9 SF have a causal relationship with CM in the training cohort. Although these 9 SF weren't confirmed in the testing cohort, 4 SF remained significant in the meta-analysis after integrating results from both cohorts. MVMR analysis indicated that 3 SF were still significantly associated with CM after accounting for the interactions between different SF in the training cohort. No reverse causal relationship was identified in RMR analysis.

A total of 9 SF were identified as having a potential causal relationship with CM; however, a large randomized controlled trial is needed to verify these results.

Alpinia oxyphylla, a perennial herb belonging to the Zingiberaceae family, has a long history of traditional medicinal use. The present study evaluated the efficacy of different concentrations of Alpinia oxyphylla essential oil (AEO) on the growth performance, serum antioxidation capacities, immune function, apparent digestibility of nutrients, and gut microbiota in fattening pigs. A total of 120 pigs were divided into five treatments, with six replicates each and four pigs per replicate. The pigs were fed a basal diet or basal diet with chlortetracycline (CTC) alone or AEO at 250, 500, and 1,000 mg/kg (referred to as groups AEO1, AEO2, and AEO3, respectively) for 35 days, preceded by a 7-day pre-feed period. The results show that there were no statistically significant differences in growth performance for any dose of AEO supplementation. AEO increased L-DLC content, total protein content and the activity of GSH in serum (p < 0.05). The AEO also exhibited a linear increase in serum IgG content (p < 0.05). Dietary supplementation with AEO improved apparent digestibility of crude ash and calcium (p < 0.05). In gut microbiota, AEO modified the diversity and abundance of bacterial communities in fattening pigs. The abundance of Dorea, Blautia, Butyricicoccus, Bulleidia, and Lactobacillus was higher in the AEO groups compared to the control group, while Clostridium and Turicibacter were lower. The Bifidobacteriales and Pseudomonas were abundant in group AEO1 and AEO3, respectively. In conclusion, dietary supplementation of 1,000 mg/kg AEO has the potential to improve growth performance, immunological, biochemical, and antioxidant statuses. Additionally, AEO can increase the efficiency of nutrient digestion and absorption through the regulation of gut microbiota.

Obesity is one of the public health issues that seriously threatens human health. This study aimed to investigate the effects of wheat bran oil (WBO) on body weight and fat/lipid accumulation in high-fat diet (HFD)-induced obese rats and further explore the possible mechanisms by microbiome and metabolome analyses.

Fifty Sprague-Dawley (SD) rats were fed either a normal chow diet (B group, n = 10) or HFD (n = 40) for 14 weeks to establish an obesity model. The HFD-induced obese rats were further divided into four groups and given WBO at 0 mL/kg (M group), 1.25 mL/kg (WBO-L group), 2.5 mL/kg (WBO-M group), and 5 mL/kg (WBO-H group) by oral gavage for 9 weeks. The body weight of rats was weighed weekly. The gut microbiota structure was analyzed using 16 S rDNA high-throughput sequencing. The liver metabolite profile was determined using UHPLC-QE-MS non-target metabolomics technology.

In this study, WBO treatment reduced body weight gain, fat and lipid accumulation, and ameliorated hepatic steatosis and inflammation. WBO treatment increased the relative abundance of Romboutsia and Allobaculum and decreased that of Candidatus_Saccharimonas, Alloprevotella, Rikenellaceae_RC9_gut_group, Alistipes, Parabacteroides, UCG-005, Helicobacter, Colidextribacter, and Parasutterella compared with the M group. A total of 22 liver metabolites were significantly altered by WBO treatment, which were mainly involved in taurine and hypotaurine metabolism, nicotinate and nicotunamide metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and ether lipid metabolism.

WBO alleviated body weight gain and fat/lipid accumulation in HFD-induced obese rats, which may be related to altered gut microbiota and liver metabolites.

Correlative studies have linked human gut microbes to specific health conditions. Alistipes is one such microbial genus negatively linked to inflammatory bowel disease (IBD). However, the protective role of Alistipes in IBD has not been studied and the underlying molecular mechanisms also remain unknown. In this study, colonization of Il10 -deficient mice with Alistipes timonensis DSM 27924 delays the development of colitis. Colonization with Alistipes does not significantly alter the gut microbiome composition during colitis development, but instead shifts the host plasma lipidome, increasing phosphatidic acids while decreasing triglycerides. Outer membrane vesicles (OMVs) derived from Alistipes are also detected in the plasma of colonized mice, which carry metabolites with immunomodulatory potential into the host circulatory system. We further demonstrate that fractions of A. timonensis OMVs suppress LPS-induced Il6 , Il1b , and Tnfa expression in vitro in murine macrophages. We detect immunomodulatory sulfonolipids (SoLs) in the active fraction, which are also increased in the blood of A. timonensis -colonized mice; and we identify other putative bioactive lipids in the A. timonensis OMVs. Thus, A. timonensis OMVs represent a potential mechanism for Alistipes -mediated delay of colitis progression in Il10 -deficient mice through the delivery of immunomodulatory lipids, including SoLs, and modulation of the host plasma lipidome.

Currently, most studies focus on the functions of probiotic-fermented milk, whereas there are relatively few studies on the function of postbiotic-fermented milk in relieving constipation. In this study, we aimed to assess the modulation of constipation symptoms and its mechanism of action by different concentrations of Lacticaseibacillus paracasei-fermented milk as a postbiotic in a loperamide hydrochloride-induced constipation model in BALB/c mice. By comparing the relevant indexes, colon histological analysis, gene expression level, and intestinal flora structure in the constipation model of mice, we found that high and ultra-high doses of fermented milk can effectively relieve constipation. Fermented milk effectively reduced defecation time, increased the rate of small intestinal propulsion in constipated mice, and alleviated colonic inflammation, safeguarding the normal function of the intestinal tract. In addition, it can regulate the intestinal flora, downregulate the abundance of Proteobacteria, upregulate the abundance of species of Firmicutes and Actinobacteriota, and improve the overall abundance level of intestinal flora in mice.

The imbalance of commensal bacteria is called dysbiosis in intestinal microflora. Secreted IgA in the intestinal lumen plays an important role in the regulation of microbiota. Although dysbiosis of gut bacteria is reported in IBD patients, it remains unclear what makes dysbiosis of their microflora. The intervention method for remedy of dysbiosis in IBD patients is not well established. In this study, we focused on the quality of human endogenous IgA and investigated whether mouse monoclonal IgA which binds to selectively colitogenic bacteria can modulate human gut microbiota with IBD patients.

IgA-bound and -unbound bacteria were sorted by MACS and cell sorter. Sorted bacteria were analyzed by 16S rRNA sequencing to investigate what kinds of bacteria endogenous IgA or mouse IgA recognized in human gut microbiota. To evaluate the effect of mouse IgA, gnotobiotic mice with IBD patient microbiota were orally administrated with mouse IgA and analyzed gut microbiota.

We show that human endogenous IgA has abnormal binding activity to gut bacteria in IBD patients. Mouse IgA can bind to human microbiota and bind to selectively colitogenic bacteria. The rW27, especially, has a growth inhibitory activity to human colitogenic bacteria. Furthermore, oral administration of mouse IgA reduced an inflammation biomarker, fecal lipocalin 2, in mice colonized with IBD patient-derived microbiota, and improved dysbiosis of IBD patient sample.

Oral treatment of mouse IgA can treat gut dysbiosis in IBD patients by modulating gut microbiota.

Understanding the cause vs consequence relationship of gut inflammation and microbial dysbiosis in inflammatory bowel diseases (IBD) requires a reproducible mouse model of human-microbiota-driven experimental colitis.

Our study demonstrated that human fecal microbiota transplant (FMT) transfer efficiency is an underappreciated source of experimental variability in human microbiota-associated (HMA) mice. Pooled human IBD patient fecal microbiota engrafted germ-free (GF) mice with low amplicon sequence variant (ASV)-level transfer efficiency, resulting in high recipient-to-recipient variation of microbiota composition and colitis severity in HMA Il-10-/- mice. In contrast, mouse-to-mouse transfer of mouse-adapted human IBD patient microbiota transferred with high efficiency and low compositional variability resulting in highly consistent and reproducible colitis phenotypes in recipient Il-10-/- mice. Engraftment of human-to-mouse FMT stochastically varied with individual transplantation events more than mouse-adapted FMT. Human-to-mouse FMT caused a population bottleneck with reassembly of microbiota composition that was host inflammatory environment specific. Mouse-adaptation in the inflamed Il-10-/- host reassembled a more aggressive microbiota that induced more severe colitis in serial transplant to Il-10-/- mice than the distinct microbiota reassembled in non-inflamed WT hosts.

Our findings support a model of IBD pathogenesis in which host inflammation promotes aggressive resident bacteria, which further drives a feed-forward process of dysbiosis exacerbated by gut inflammation. This model implies that effective management of IBD requires treating both the dysregulated host immune response and aggressive inflammation-driven microbiota. We propose that our mouse-adapted human microbiota model is an optimized, reproducible, and rigorous system to study human microbiome-driven disease phenotypes, which may be generalized to mouse models of other human microbiota-modulated diseases, including metabolic syndrome/obesity, diabetes, autoimmune diseases, and cancer. Video Abstract.

Humans produce 350 million metric tons of plastic waste per year, leading to microplastic pollution and widespread environmental contamination, particularly in aquatic environments. This subsequently impacts aquatic organisms in myriad ways, yet the vast majority of research is conducted in marine, rather than freshwater systems. In this study, we exposed eggs and hatchlings of the Chinese soft-shelled turtle (Pelodiscus sinensis) to 80-nm polystyrene nanoplastics (PS-NPs) and monitored the impacts on development, behavior and the gut microbiome. We demonstrate that 80-nm PS-NPs can penetrate the eggshell and move into developing embryos. This led to metabolic impairments, as evidenced by bradycardia (a decreased heart rate), which persisted until hatching. We found no evidence that nanoplastic exposure affected hatchling morphology, growth rates, or levels of boldness and exploration, yet we discuss some potential caveats here. Exposure to nanoplastics reduced the diversity and homogeneity of gut microbiota in P. sinensis, with the level of disruption correlating to the length of environmental exposure (during incubation only or post-hatching also). Thirteen core genera (with an initial abundance >1 %) shifted after nanoplastic treatment: pathogenic bacteria increased, beneficial probiotic bacteria decreased, and there was an increase in the proportion of negative correlations between bacterial genera. These changes could have profound impacts on the viability of turtles throughout their lives. Our study highlights the toxicity of environmental NPs to the embryonic development and survival of freshwater turtles. We provide insights about population trends of P. sinensis in the wild, and future directions for research.

Edible plant-derived nanovesicles (ePDNs) have shown potential as a non-pharmacological option for inflammatory bowel disease (IBD) by maintaining gut health and showing anti-inflammatory effects. However, the effects of Allium tuberosum-derived nanovesicles (ADNs) on colitis have not been studied to date. Here, we extracted exosome-like nanovesicles from Allium tuberosum and investigated whether they have an anti-inflammatory effect in RAW 264.7 cells and colitis mice. The results showed that ADNs reduced the elevated levels of inflammatory factors such as IL-1β, IL-6, TNF-α, and NF-κB pathway-related proteins as a consequence of lipopolysaccharide (LPS) stimulation in RAW 264.7 cells. Furthermore, our mouse experiments demonstrated that ADNs could ameliorate dextran sulfate sodium (DSS)-induced colitis symptoms (e.g., increased disease activity index score, intestinal permeability, and histological appearance). Additionally, ADNs counteracted DSS-induced colitis by downregulating the expression of serum amyloid A (SAA), IL-1β, IL-6, and TNF-α and increasing the expression of tight junction proteins (ZO-1 and occludin) and the anti-inflammatory cytokine IL-10. 16S rRNA gene sequencing showed that ADN intervention restored the gut microbial composition, which was similar to that of the DSS non-treated group, by decreasing the ratio of Firmicutes to Bacteroidetes and the relative abundance of Proteobacteria. Furthermore, ADNs induced acetic acid production along with an increase in the abundance of Lactobacillus. Overall, our findings suggest that ADN supplementation has a crucial role in maintaining gut health and is a novel preventive therapy for IBD.

Gut microbiota plays a crucial role in human health homeostasis, and the result of its alteration, known as dysbiosis, leads to several pathologies (e.g., inflammatory bowel disease, metabolic syndrome, and Crohn's disease). Traditional methods used to assess dysbiosis include the dual sugar absorption test and the urinary lactulose/mannitol ratio (LMR) measurement using mass spectrometry. Despite its precision, this approach is costly and requires specialized equipment. Hence, we developed a rapid and reliable spectrofluorimetric method for measuring LMR in urine, offering a more accessible alternative. This spectrofluorimetric assay quantifies the fluorescence of nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH) produced during the enzymatic oxidation of mannitol and lactulose, respectively. The assay requires 100 µL of urine samples and detects LMR values lower (eubiosis) and higher (dysbiosis) than 0.05, ultimately being amenable to high-throughput screening and automatization, making it practical for clinical and research settings. A validation of the method demonstrated its high precision, accuracy, and robustness. Additionally, this study confirmed analyte stability under various storage conditions, ensuring reliable results even with delayed analysis. Overall, this spectrofluorimetric technique reduces costs, time, and the environmental impact associated with traditional mass spectrometry methods, making it a viable option for widespread use in the assessment of dysbiosis.

Acupuncture, an important green and side effect-free therapy in traditional Chinese medicine, is widely use both domestically and internationally. Acupuncture can interact with the gut microbiota and influence various diseases, including metabolic diseases, gastrointestinal diseases, mental disorders, nervous system diseases, and other diseases. This review presents a thorough analysis of these interactions and their impacts and examines the alterations in the gut microbiota and the potential clinical outcomes following acupuncture intervention to establish a basis for the future utilization of acupuncture in clinical treatments.

The calf's gastrointestinal tract (GIT) microbiome undergoes rapid shifts during early post-natal life, which can directly affect calf performance. The objectives of this study were to characterise and compare differences in the establishment and succession of GIT microbiota, GIT morphological changes, and the growth of dairy calves from birth until weaned. Forty-four newborn Holstein-Friesian calves were randomly selected and assigned to Treatment (TRT) and Control (CON) groups. The TRT group calves received a once-daily dose of a direct-fed microbial (DFM) liquid product containing Lacticaseibacillus paracasei, Lentilactobacillus buchneri, and Lacticaseibacillus casei, all formerly known as Lactobacillus. Fresh faecal samples were manually taken from the rectum of all calves, and gross necropsy was performed on the forestomachs and gastrointestinal tracts. Bacterial DNA was extracted from frozen faecal samples for 16S rRNA gene amplicon sequencing. Calves in the TRT group had greater live weights (p = 0.02) at weaning compared with calves in the CON group (mean = 69.18 kg, SD = 13.37 kg). The average daily live weight gain (ADG) and total feed intake were similar between the two groups. Calves in the TRT group had greater duodenum, abomasum, and reticulum weights (p = 0.05). Rumen and intestinal development (p < 0.05) and faecal microbial diversity (p < 0.05) were more pronounced in the TRT group. The relative abundances of eight genera differed (p < 0.001) between the groups. Supplementing calves with the LAB-based DFM increased live weight at weaning and had a more pronounced effect on the development of rumen and the gastrointestinal tract and on microbiota diversity and evenness. Future work is needed to better understand the potential association of LAB-DFM products on gut mucosa-associated microbiota.

Huntington's disease (HD) is a neurodegenerative disorder involving psychiatric, cognitive and motor deficits, as well as peripheral symptoms, including gastrointestinal dysfunction. The R6/1 HD mouse model expresses a mutant human huntingtin transgene and has been shown to provide an accurate disease model. Recent evidence of gut microbiome disruption was shown in preclinical and clinical HD. Therefore, we aimed to assess the potential role of gut microbial modulation in the treatment of HD. The R6/1 HD mice and wild-type littermate controls were randomised to receive diets containing different amounts of fibre: high-fibre (10 % fibre), control (5 % fibre), or zero-fibre (0 % fibre), from 6 to 20 weeks of age. We characterized the onset and progression of motor, cognitive and affective deficits, as well as gastrointestinal function and gut morphological changes. Faeces were collected for gut microbiome profiling using 16S rRNA sequencing, at 14 and 20 weeks of age. When compared to the control diet, high-fibre diet improved the performance of HD mice in behavioral tests of cognitive and affective function, as well as the gastrointestinal function of both HD and wild-type mice. While the diets changed the beta diversity of wild-type mice, no statistical significance was observed at 14 or 20 weeks of age within the HD mice. Analysis of Composition of Microbiomes with Bias Correction (ANCOM-BC) models were performed to evaluate microbiota composition, which identified differences, including a decreased relative abundance of the phyla Actinobacteriota, Campylobacterota and Proteobacteria and an increased relative abundance of the families Bacteroidaceae, Oscillospiraceae and Ruminococcaceae in HD mice when compared to wild-type mice after receiving high-fibre diet. PICRUSt2 revealed that high-fibre diet also decreased potentially pathogenic functional pathways in HD. In conclusion, high-fibre intake was effective in enhancing gastrointestinal function, cognition and affective behaviors in HD mice. These findings indicate that dietary fibre interventions may have therapeutic potential in Huntington's disease to delay clinical onset, and have implications for related disorders exhibiting dysfunction of the gut-brain axis.

Understanding the cause vs consequence relationship of gut inflammation and microbial dysbiosis in inflammatory bowel diseases (IBD) requires a reproducible mouse model of human-microbiota-driven experimental colitis. Our study demonstrated that human fecal microbiota transplant (FMT) transfer efficiency is an underappreciated source of experimental variability in human microbiota associated (HMA) mice. Pooled human IBD patient fecal microbiota engrafted germ-free (GF) mice with low amplicon sequence variant (ASV)-level transfer efficiency, resulting in high recipient-to-recipient variation of microbiota composition and colitis severity in HMA Il-10-/- mice. In contrast, mouse-to-mouse transfer of mouse-adapted human IBD patient microbiota transferred with high efficiency and low compositional variability resulting in highly consistent and reproducible colitis phenotypes in recipient Il-10-/- mice. Human-to-mouse FMT caused a population bottleneck with reassembly of microbiota composition that was host inflammatory environment specific. Mouse-adaptation in the inflamed Il-10-/- host reassembled a more aggressive microbiota that induced more severe colitis in serial transplant to Il-10-/- mice than the distinct microbiota reassembled in non-inflamed WT hosts. Our findings support a model of IBD pathogenesis in which host inflammation promotes aggressive resident bacteria, which further drives a feed-forward process of dysbiosis exacerbated gut inflammation. This model implies that effective management of IBD requires treating both the dysregulated host immune response and aggressive inflammation-driven microbiota. We propose that our mouse-adapted human microbiota model is an optimized, reproducible, and rigorous system to study human microbiome-driven disease phenotypes, which may be generalized to mouse models of other human microbiota-modulated diseases, including metabolic syndrome/obesity, diabetes, autoimmune diseases, and cancer.

Ulcerative colitis is a chronic inflammatory disease with a complex pathogenesis for which there is no definitive therapeutic agent. Fermentation, as a green and efficient bioprocessing technique, has been shown to enhance the biological activity of food ingredients. Soluble dietary fiber isolated from plants is thought to have the potential to prevent and alleviate ulcerative colitis. This work was designed to study the differences in the chemical properties of the soluble dietary fiber from wheat bran fermented by Isaria cicadae Miq. (FSDF) and the unfermented soluble dietary fiber from wheat bran (UFSDF) and their effects on colitis mice. The results showed that FSDF and UFSDF differed in molecular weight, monosaccharide compositions, and surface morphology. In addition, supplementation with UFSDF and FSDF ameliorated the symptoms of DSS-induced colitis in mice by attenuating body weight loss, decreasing the disease activity index and splenic index, shortening the length of the colon, and attenuating colonic tissue damage. UFSDF and FSDF also increased the production of the anti-inflammatory cytokine IL-10 and inhibited the expression of IL-6, IL-1β, and TNF-α. The results of gut flora and short-chain fatty acid analyses showed that UFSDF and FSDF improved the diversity of gut microbiota, up-regulated the abundance of some beneficial bacteria such as Akkermansia and Muribaculaceae, increased the levels of acetic acid, propionic acid, and butyric acid, and restored dextran sodium sulfate (DSS)-induced dysbiosis of the intestinal flora in mice. These findings provide guidance for the development of FSDF and UFSDF as functional foods for the relief of ulcerative colitis.

The intestine is the largest organ in terms of surface area in the human body. It is responsible not only for absorbing nutrients but also for protection against the external world. The gut microbiota is essential in maintaining a properly functioning intestinal barrier, primarily through producing its metabolites: short-chain fatty acids, bile acids, and tryptophan derivatives. Ethanol overconsumption poses a significant threat to intestinal health. Not only does it damage the intestinal epithelium, but, maybe foremostly, it changes the gut microbiome. Those ethanol-driven changes shift its metabolome, depriving the host of the protective effect the physiological gut microbiota has. This literature review discusses the impact of ethanol consumption on the gut, the gut microbiota, and its metabolome, providing a comprehensive overview of the mechanisms through which ethanol disrupts intestinal homeostasis and discussing potential avenues for new therapeutic intervention.

Whether nanoplastics with differential charges cause intestinal impairment via distinct mechanisms remains unclear. We investigated the relationship between fecal metabolites and the gut microbiome, and potential biomarkers thereof, in mice following exposure to differentially charged polystyrene nanoplastics (PS-NPs). Metagenomic analysis revealed that exposure to differentially charged PS-NPs resulted in alterations in the abundances of Bilophila_wadsworthia, Helicobacter apodemus, and Helicobacter typhlonius. A total of 237 fecal metabolites were significantly altered in mice that exhibited intestinal impairment, and these included 10 gut microbiota-related fecal metabolites that accurately discriminated impaired intestinal samples from the control. Additionally, the specific gut microbiome-related fecal metabolite-based model approach for the prediction of intestinal impairment in mice had an area under the curve (AUC) of 1.0 in the PS (without charge) group, an AUC of 0.94 in the PS-NH2 (positive charge) group, and an AUC of 0.86 in the PS-COOH (negative charge) group. Thus, the model showed promising evaluable accuracy for the prediction of intestinal impairment induced by nanoplastics in a charge-specific manner. Our study demonstrates that the fecal metabolome of mice with intestinal impairment following exposure to differentially charged nanoplastics is associated with changes in the gut microbiome. The identified biomarkers have potential application for the detection of intestinal impairment after exposure to negative, positive, or noncharged nanomaterials.

Inflammatory bowel disease (IBD) patients experience recurrent episodes of intestinal inflammation and often follow an unpredictable disease course. Mucosal colonization with adherent-invasive Escherichia coli (AIEC) are believed to perpetuate intestinal inflammation. However, it remains unclear if the 24-year-old AIEC in vitro definition fully predicts mucosal colonization in vivo. To fill this gap, we have developed a novel molecular barcoding approach to distinguish strain variants in the gut and have integrated this approach to explore mucosal colonization of distinct patient-derived E. coli isolates in gnotobiotic mouse models of colitis.

Germ-free inflammation-susceptible interleukin-10-deficient (Il10-/-) and inflammation-resistant WT mice were colonized with a consortium of AIEC and non-AIEC strains, then given a murine fecal transplant to provide niche competition. E. coli strains isolated from human intestinal tissue were each marked with a unique molecular barcode that permits identification and quantification by barcode-targeted sequencing. 16S rRNA sequencing was used to evaluate the microbiome response to E. coli colonization. Our data reveal that specific AIEC and non-AIEC strains reproducibly colonize the intestinal mucosa of WT and Il10-/- mice. These E. coli expand in Il10-/- mice during inflammation and induce compositional dysbiosis to the microbiome in an inflammation-dependent manner. In turn, specific microbes co-evolve in inflamed mice, potentially diversifying E. coli colonization patterns. We observed no selectivity in E. coli colonization patterns in the fecal contents, indicating minimal selective pressure in this niche from host-microbe and interbacterial interactions. Because select AIEC and non-AIEC strains colonize the mucosa, this suggests the in vitro AIEC definition may not fully predict in vivo colonization potential. Further comparison of seven E. coli genomes pinpointed unique genomic features contained only in highly colonizing strains (two AIEC and two non-AIEC). Those colonization-associated features may convey metabolic advantages (e.g., iron acquisition and carbohydrate consumption) to promote efficient mucosal colonization.

Our findings establish the in vivo mucosal colonizer, not necessarily AIEC, as a principal dysbiosis driver through crosstalk with host and associated microbes. Furthermore, we highlight the utility of high-throughput screens to decode the in vivo colonization dynamics of patient-derived bacteria in murine models. Video Abstract.

Necrotizing enterocolitis (NEC) is a significant cause of morbidity and mortality among neonates and low birth weight children in the United States. Current treatment options, such as antibiotics and intestinal resections, often result in complications related to pediatric nutrition and development. This systematic review aimed to identify alternative dietary bioactive compounds that have shown promising outcomes in ameliorating NEC in vivo studies conducted within the past six years. Following PRISMA guidelines and registering in PROSPERO (CRD42023330617), we conducted a comprehensive search of PubMed, Scopus, and Web of Science. Our analysis included 19 studies, predominantly involving in vivo models of rats (Rattus norvegicus) and mice (Mus musculus). The findings revealed that various types of compounds have demonstrated successful amelioration of NEC symptoms. Specifically, six studies employed plant phenolics, seven utilized plant metabolites/cytotoxic chemicals, three explored the efficacy of vitamins, and three investigated the potential of whole food extracts. Importantly, all administered compounds exhibited positive effects in mitigating the disease. These results highlight the potential of natural cytotoxic chemicals derived from medicinal plants in identifying and implementing powerful alternative drugs and therapies for NEC. Such approaches have the capacity to impact multiple pathways involved in the development and progression of NEC symptoms.

The intestinal barrier maintains intestinal homeostasis and metabolism and protects against harmful pollutants. Some environmental pollutants seriously affect intestinal barrier function. However, it remains unclear whether or how chlorothalonil (CTL) impacts the intestinal barrier function in animals. Herein, 6-week-old male mice were acutely exposed to different CTL concentrations (100 and 300 mg/kg BW) via intragastric administration once a day for 7 days. Histopathological examination revealed obvious inflammation in the mice' colon and ileum. Most notably, CTL exposure increased the intestinal permeability, particularly in the CTL-300 group. CTL exposure reduced the secretion of colonic epithelial mucus and changed the transcription levels of genes bound up with ion transport and ileal antimicrobial peptide (AMP) secretion, indicating intestinal chemical barrier damage. The results of terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay and Ki67 staining revealed abnormal apoptosis and increased intestinal epithelial cell proliferation, suggesting that CTL exposure led to cytotoxicity and inflammation. The results of 16S rRNA sequencing revealed that CTL exposure altered the intestinal microbiota composition and reduced its diversity and richness in the colon contents. Thus, acute CTL exposure affected the different intestinal barrier- and gut microenvironment-related endpoints in mice.

Soil ingestion by livestock is common in grazing ecosystems, but few studies have been conducted to assess its effect on the animal organism. The topic is worthy of attention because these potential effects are likely to be enriched in the food chain and interfere with animal and human health. In this study, we present an indoor feeding trial conducted based on a completely randomized design to comprehensively evaluate the effects of simulated soil ingestion during grazing on nutrient digestibility, rumen fermentation, and microflora, and mineral deposition in the organs and tissues of sheep. Eighteen Mutton Merino crossbred sheep (42.7 ± 2.34 kg) were randomly allotted to three treatments and fed diets containing 0% (Control), 5% (SOIL5), and 10% (SOIL10) for 62 d, including a 7-d metabolism trial. It was found that soil intake altered the rumen fermentation in sheep, as evidenced by a decrease in total volatile fatty acids (VFA) and acetate concentrations in rumen fluid of 50.6% and 51.3%, respectively (p < 0.01), with soil proportion in the diet increased from 0% to 10%. Soil ingestion also reduced the species richness of rumen bacteria, with the relative abundance of Bacteroidetes decreasing significantly (p < 0.01), while that of Firmicutes and Proteobacteria increased considerably (p < 0.05). In terms of mineral elements deposition, higher levels of iron (Fe) were detected in the spleen and liver, and a higher concentration of copper (Cu) and zinc (Zn) in the liver were found in sheep fed a diet containing 5% soil compared to the other two groups (p < 0.05). Moreover, the concentrations of lead (Pb) in the liver and kidney, and arsenic (As) in the heart were also clearly increased after ingestion of soil (p < 0.05). Our findings indicate that although soil intake had no significant effect on the growth performance of sheep, it altered ruminal fermentation and increased the risk of excessive Fe, Pb, and As in their organism. This study supplies a theoretical basis for risk assessment of soil ingestion in grazing livestock.

Eighty percent of antibody secreting cells (ASCs) are found in the intestine, where they produce grams of immunoglobulin (Ig) A daily. immunoglobulin A is actively transcytosed into the lumen, where it plays a critical role in modulating the gut microbiota. Although loss of immune tolerance to bacterial antigens is the likely trigger of the dysregulated immune response that characterizes inflammatory bowel disease (IBD), little effort has been placed on understanding the interface between B cells, IgA, and the microbiota during initiation or progression of disease. This may be in part due to the misleading fact that IgA-deficient humans are mostly asymptomatic, likely due to redundant role of secretory (S) IgM. Intestinal B cell recruitment is critically dependent on integrin α4β7-MAdCAM-1 interactions, yet antibodies that target α4β7 (ie, vedolizumab), MAdCAM-1 (ie, ontamalimab), or both β7 integrins (α4β7 and αE [CD103] β7; etrolizumab) are in clinical use or development as IBD therapeutics. The effect of such interventions on the biology of IgA is largely unknown, yet a single dose of vedolizumab lowers SIgA levels in stool and weakens the oral immunization response to cholera vaccine in healthy volunteers. Thus, it is critical to further understand the role of these integrins for the migration of ASC and other cellular subsets during homeostasis and IBD-associated inflammation and the mode of action of drugs that interfere with this traffic. We have recently identified a subset of mature ASC that employs integrin αEβ7 to dock with intestinal epithelial cells, predominantly in the pericryptal region of the terminal ileum. This role for the integrin had not been appreciated previously, nor the αEβ7-dependent mechanism of IgA transcytosis that it supports. Furthermore, we find that B cells more than T cells are critically dependent on α4β7-MAdCAM-1 interactions; thus MAdCAM-1 blockade and integrin-β7 deficiency counterintuitively hasten colitis in interleukin-10-deficient mice. In both cases, de novo recruitment of IgA ASC to the intestinal lamina propria is compromised, leading to bacterial overgrowth, dysbiosis, and lethal colitis. Thus, despite the safe and effective use of anti-integrin antibodies in patients with IBD, much remains to be learned about their various cell targets.

The intestinal mucosa is continually exposed to diverse microbial and dietary Ags, requiring coordinated efforts by specialized populations of regulatory T cells (Tregs) to maintain homeostasis. Suppressive mechanisms used by intestinal Tregs include the secretion of anti-inflammatory cytokines such as IL-10 and TGF-β. Defects in IL-10 signaling are associated with severe infantile enterocolitis in humans, and mice deficient in IL-10 or its receptors develop spontaneous colitis. To determine the requirement of Foxp3+ Treg-specific IL-10 for protection against colitis, we generated Foxp3-specific IL-10 knockout (KO) mice (IL-10 conditional KO [cKO] mice). Colonic Foxp3+ Tregs isolated from IL-10cKO mice showed impaired ex vivo suppressive function, although IL-10cKO mice maintained normal body weights and developed only mild inflammation over 30 wk of age (in contrast to severe colitis in global IL-10KO mice). Protection from colitis in IL-10cKO mice was associated with an expanded population of IL-10-producing type 1 Tregs (Tr1, CD4+Foxp3-) in the colonic lamina propria that produced more IL-10 on a per-cell basis compared with wild-type intestinal Tr1 cells. Collectively, our findings reveal a role for Tr1 cells in the gut, as they expand to fill a tolerogenic niche in conditions of suboptimal Foxp3+ Treg-mediated suppression and provide functional protection against experimental colitis.

The gut microbiome is clearly linked to the development of various autoimmune diseases, however, its association with immune thrombocytopenia (ITP) is less well understood. The current study collected 73 samples, including 36 from healthy individuals and 37 from ITP patients. The gut microbial community was assessed using 16s rRNA sequencing. Findings illustrated that the abundance of key microbiota was significantly higher in the ITP group. This group was further divided into three subgroups that received different treatments for ITP. A random forest model was used to predict the key microbiota and the identified bacteria were shown to easily distinguish between the healthy and the ITP treatment groups. Microbial function annotation and difference analysis showed that drug treatment changed the gut microbiota and may play a role in inducing host autoimmune responses by changing microbial metabolism pathways. Clinical indices also correlated negatively with changes in the microbiota after treatment. In summary, ITP patients who received drug treatment had significant differences in their microbiota along with a high abundance of bacteria. Thus, the microbiome could be used as a biomarker to distinguish between healthy and ITB groups. The key differential bacteria could help to regulate the number of platelets in ITP patients and provide a red blood cell overstock.

Inflammatory bowel disease (IBD) patients experience recurrent episodes of intestinal inflammation and often follow an unpredictable disease course. Mucosal colonization with adherent-invasive Escherichia coli (AIEC) are believed to perpetuate intestinal inflammation. However, it remains unclear if the 24-year-old AIEC in-vitro definition fully predicts mucosal colonization in-vivo. To fill this gap, we have developed a novel molecular barcoding approach to distinguish strain variants in the gut and have integrated this approach to explore mucosal colonization of distinct patient-derived E. coli isolates in gnotobiotic mouse models of colitis.

Germ-free inflammation-susceptible interleukin-10-deficient (Il10-/-) and inflammation-resistant WT mice were colonized with a consortia of AIEC and non-AIEC strains, then given a murine fecal transplant to provide niche competition. E. coli strains isolated from human intestinal tissue were each marked with a unique molecular barcode that permits identification and quantification by barcode-targeted sequencing. 16S rRNA sequencing was used to evaluate the microbiome response to E. coli colonization. Our data reveal that specific AIEC and non-AIEC strains reproducibly colonize the intestinal mucosa of WT and Il10-/- mice. These E. coli expand in Il10-/- mice during inflammation and induce compositional dysbiosis to the microbiome in an inflammation-dependent manner. In turn, specific microbes co-evolve in inflamed mice, potentially diversifying E. coli colonization patterns. We observed no selectivity in E. coli colonization patterns in the fecal contents, indicating minimal selective pressure in this niche from host-microbe and interbacterial interactions. Because select AIEC and non-AIEC strains colonize the mucosa, this suggests the in vitro AIEC definition may not fully predict in vivo colonization potential. Further comparison of seven E. coli genomes pinpointed unique genomic features contained only in highly colonizing strains (two AIEC and two non-AIEC). Those colonization-associated features may convey metabolic advantages (e.g., iron acquisition and carbohydrate consumption) to promote efficient mucosal colonization.

Our findings establish the in-vivo mucosal colonizer, not necessarily AIEC, as a principal dysbiosis driver through crosstalk with host and associated microbes. Furthermore, we highlight the utility of high-throughput screens to decode the in-vivo colonization dynamics of patient-derived bacteria in murine models.

Despite Toxoplasma gondii infection leading to dysbiosis and enteritis, the function of gut microbiota in toxoplasmosis has not been explored.

Here, shotgun metagenomics was employed to characterize the composition and function of mouse microbial community during acute and chronic T. gondii infection, respectively.

The results revealed that the diversity of gut bacteria was decreased immediately after T. gondii infection, and was increased with the duration of infection. In addition, T. gondii infection led to gut microbiota dysbiosis both in acute and chronic infection periods. Therein, several signatures, including depression of Firmicutes to Bacteroidetes ratio and infection-enriched Proteobacteria, were observed in the chronic period, which may contribute to aggravated gut inflammation and disease severity. Functional analysis showed that a large amount of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and carbohydrate-active enzymes (CAZy) family displayed distinct variation in abundance between infected and healthy mice. The lipopolysaccharide biosynthesis related pathways were activated in the chronic infection period, which might lead to immune system imbalance and involve in intestinal inflammation. Moreover, microbial and functional spectrums were more disordered in chronic than acute infection periods, thus implying gut microbiota was more likely to participate in disease process in the chronically infected mice, even exacerbated immunologic derangement and disease progression.

Our data indicate that the gut microbiota plays a potentially important role in protecting mice from T. gondii infection, and contributes to better understand the association between gut microbiota and toxoplasmosis.

Inflammatory bowel disease (IBD) is a non-specific chronic inflammatory disease of the intestine. In addition to genetic susceptibility, environmental factors and dysregulated host immunity, the gut microbiota is implicated in the pathogenesis of Crohn's disease (CD) or ulcerative colitis (UC), the two primary types of IBD. The P2X4 receptor has been demonstrated to have a crucial role in preventing infection, inflammation, and organ damage. However, it remains unclear whether the P2X4 receptor affects IBD and the underlying mechanisms.

Colitis was induced in mice administrated with dextran sodium sulphate (DSS). 16S rDNA sequencing was used to analyze the gut microbiota in knockout and wild-type mice. Clinical and histopathological parameters were monitored throughout the disease progression.

Gene Expression Omnibus analysis showed the downregulation of P2RX4 (P2rx4) expression in colonic tissues from patients or mice with IBD. However, its expression at the protein levels was upregulated on day 4 or 6 and then downregulated on day 7 in C57BL/6 mice treated with DSS. Gene ablation of P2rx4 aggravated DSS-induced colitis accompanying gut microbiota dysbiosis in mice. Moreover, P2X4 receptor-positive modulator ivermectin alleviated colitis and corrected dysregulated microbiota in wild-type C57BL/6 mice. Further antibiotic-treated gut microbiota depletion, cohousing experiment, and fecal microbiota transplantation proved that gut microbiota dysbiosis was associated with the aggravation of colitis in the mouse model initiated by P2rx4.

Our findings elaborate on an unrevealed etiopathophysiological mechanism by which microbiota dysbiosis induced by the P2X4 receptor influences the development of colitis, indicating that the P2X4 receptor represents a promising target for treating patients with CD and UC.

Mice lacking IL-10 are prone to gut inflammation. Additionally, decreased production of short-chain fatty acids (SCFAs) plays a significant role in the high-fat (HF) diet-induced loss of gut epithelial integrity. We have previously shown that wheat germ (WG) supplementation increased ileal expression of IL-22, an important cytokine in maintaining gut epithelial homeostasis.

This study investigated the effects of WG supplementation on gut inflammation and epithelial integrity in IL-10 knockout mice fed a pro-atherogenic diet.

Eight-week-old female C57BL/6 wild type mice were fed a control diet (10% fat kcal), and age-matched knockout mice were randomly assigned to 1 of 3 diets (n = 10/group): control, high-fat high-cholesterol (HFHC) [(43.4% fat kcal (∼49% saturated fat, 1% cholesterol)], or HFHC + 10% WG (HFWG) for 12 wk. Fecal SCFAs and total indole, ileal, and serum proinflammatory cytokines, gene or protein expression of tight junctions, and immunomodulatory transcription factors were assessed. Data were analyzed by 1-way ANOVA, and P < 0.05 was considered statistically significant.

Fecal acetate, total SCFAs, and indole increased (P < 0.05) by at least 20% in HFWG compared with the other groups. WG increased (P < 0.0001, 2-fold) ileal Il22 (interleukin 22) to Il22ra2 (interleukin 22 receptor, alpha 2) mRNA ratio and prevented the HFHC diet-mediated increase in ileal protein expression of indoleamine 2,3 dioxygenase and pSTAT3 (phosphorylated signal transducer and activator of transcription 3). WG also prevented the HFHC diet-mediated reduction (P < 0.05) in ileal protein expression of the aryl hydrocarbon receptor and the tight junction protein, zonula occludens-1. Serum and ileal concentrations of the proinflammatory cytokine, IL-17, were lower (P < 0.05) by at least 30% in the HFWG group than in the HFHC group.

Our findings demonstrate that the anti-inflammatory potential of WG in IL-10 KO mice consuming an atherogenic diet is partly attributable to its effects on the IL-22 signaling and pSTAT3-mediated production of T helper 17 proinflammatory cytokines.

Intestinal colonization of the oral bacterium Haemophilus parainfluenzae has been associated with Crohn's disease (CD) severity and progression. This study examines the role of periodontal disease (PD) as a modifier for colonization of H. parainfluenzae in patients with CD and explores the mechanisms behind H. parainfluenzae-mediated intestinal inflammation. Fifty subjects with and without CD were evaluated for the presence of PD, and their oral and fecal microbiomes were characterized. PD is associated with increased levels of H. parainfluenzae strains in subjects with CD. Oral inoculation of H. parainfluenzae elicits strain-dependent intestinal inflammation in murine models of inflammatory bowel disease, which is associated with increased intestinal interferon-γ (IFN-γ)+ CD4+ T cells and disruption of the host hypusination pathway. In summary, this study establishes a strain-specific pathogenic role of H. parainfluenzae in intestinal inflammation and highlights the potential effect of PD on intestinal colonization by pathogenic H. parainfluenzae strains in patients with CD.