Paneth cells secrete antimicrobial peptides (AMPs) to modulate composition of gut microbiota and host defense. AMPs are typically packaged into dense core vesicles (DCVs) and secreted into the intestinal lumen. However, the mechanisms underlying DCV biogenesis and secretion are still elusive. Here we identified that ERAdP was highly expressed in Paneth cells that acted as a sensor for a bacterial second messenger c-di-AMP. ERAdP deficiency caused impaired DCV biogenesis and dysfunction of Paneth cells. Mechanistically, by sensing c-di-AMP, ERAdP interacted with NLRP6 and further recruited ANXA2 onto the DCV membrane in Paneth cells. The ERAdP-NLRP6-ANXA2 complex facilitated DCV biogenesis, which enhanced antibacterial ability of intestines. Disruption of ERAdP-NLRP6-ANXA2 axis led to loss of DCVs in Paneth cells and increased susceptibility to bacterial infection. Of note, ERAdP-NLRP6-ANXA2 proteins were lowly expressed in IBD patients, and c-di-AMP treatment enhanced antibacterial capacity in antibiotic-treated mice. Our findings reveal that c-di-AMP stimulation might provide a potential therapeutic strategy for infectious disease and gut inflammation.

Effects of alcohol use on the gut, inflammation, and organ injury: A summary of the 2025 Alcohol and Immunology Research Interest Group (AIRIG) meeting.

Oral administration of probiotics holds great promise for regulating gut microbiota and maintaining intestinal homeostasis. However, its practical effectiveness can be limited due to the digestive tract's harsh environment. Natural polysaccharide-based hydrogel microsphere systems are increasingly used for probiotic protection and oral delivery; the conventional materials used in these systems exhibit defects such as poor structural strength and instability in gelation, causing premature probiotic release. Here, we created hydrogel microspheres with gut-adaptive structures (GG/GN-TA HMs) using gellan gum (GG) as the backbone and β-glucan-tannic acid (GN-TA) as the antioxidative, adhesive, and gut-targeting prebiotic donor, involving structural enhancement via TA-Ca2+ metal-phenol networks during cross-linking. The structurally optimized microspheres exhibited excellent structural integrity at low pH conditions while disassembling in the gut environment to release probiotics. Such advantages of GG/GN-TA HMs enabled the survival of probiotics in harsh environments and subsequent promotion of probiotic colonization in the colon. In colitis mice, EcN@GG/GN-TA exhibited superior therapeutic effects compared to those of other groups. GG/GN-TA HMs promoted probiotic-prebiotic synergy, which resulted in significant alleviation of gut inflammation, gut barrier repair, and gut microbiota remodeling. Given its simple preparation and efficacy, the GG/GN-TA HMs system has great potential for the protection and targeted delivery of probiotics.

Background The pathogenesis of gestational diabetes mellitus (GDM) is not fully understood, with gut microbiota dysbiosis emerging as a potential contributing factor. Existing animal models primarily mimic type 1 or type 2 diabetes, inadequately representing GDM. This study aimed to investigate whether fecal microbiota transplantation (FMT) from GDM patients is associated with the development of GDM-like phenotypes in mice, comparing this approach to traditional modeling methods. Methods Fecal microbiota from GDM patients and healthy controls were transplanted into antibiotic-treated pregnant mice, creating trimester-specific FMT models. Control groups included mice on a high-fat diet (HFD) and HFD combined with streptozotocin (STZ). Metabolic phenotypes were assessed via glucose and insulin tolerance tests, fasting blood glucose, and insulin measurements. Serum inflammatory markers were analyzed, and gut inflammation was evaluated. 16S rRNA sequencing was performed on key model groups. Results Mice receiving FMT from mid-late trimester GDM donors or traditional treatments developed significant glucose intolerance, insulin resistance, and gestational weight gain. Serum levels of inflammatory factors (e.g., IL-1β, MMP-9) were elevated. 16S rRNA sequencing revealed markedly reduced gut microbiota diversity and increased Firmicutes/Bacteroidota ratio in both GDM-FMT and traditional model groups, with similar microbial community structures and alterations in metabolic and inflammation-related pathways. Conclusion Gut microbiota from GDM patients may disrupt glucose homeostasis and contribute to a pro-inflammatory state during pregnancy. The GDM-FMT model effectively recapitulates key metabolic, inflammatory, and microbial dysbiosis features of GDM, providing a novel and reliable experimental tool for mechanistic studies.

This review delves into the complex relationship between short-chain fatty acids (SCFAs) produced by the gut microbiota and inflammatory bowel disease (IBD). IBD, which includes Crohn's disease and ulcerative colitis, is a group of chronic gastrointestinal disorders with an increasing global incidence. Despite extensive research, the exact etiopathogenesis remains elusive, although a complex interplay involving genetic predisposition, environmental influences, and abnormal immune responses against commensal gut microbes is widely recognized. SCFAs, primarily acetate and butyrate, emerge as key microbial metabolites derived from the fermentation of dietary fiber. They exert profound effects on gut homeostasis, notably with butyrate serving as an essential energy source for colonocytes, strengthening epithelial integrity, actively modulating local and systemic immune functions, suppressing the expression of pro-inflammatory cytokines, and enhancing mucosal defense mechanisms. However, clinical trials exploring SCFA administration have frequently yielded variable and inconsistent results due to differences in study design and patient characteristics. This review thoroughly analyzes the diverse roles of SCFAs in the large intestine, focusing on the intestinal barrier, immune modulation, and microbiota. It critically examines the therapeutic potential of SCFAs, including acetate and propionate, in addition to the well-known butyrate, in IBD management.

Abstract Oral conditions such as periodontitis are associated with extra-oral diseases, including inflammatory bowel disease (IBD). Approximately 50% of IBD patients present with oral manifestations, which correlate with worse clinical outcomes. However, the persistence of oral inflammation-imprinted risk remains poorly understood. Here, we investigated the long-term impact of oral inflammation on IBD susceptibility and the mechanisms linking oral-gut mucosal inflammation. Oral inflammation was induced in mice using ligature-induced periodontitis (LIP). After ligature removal and recovery (LIP-R), mice remained more susceptible to DSS-induced colitis than controls, indicating that not only active but also past oral inflammation confers persistent susceptibility to gut inflammation. This inflammatory memory response persisted in Rag1-deficient mice, which lack adaptive immunity. Analysis of immune alterations revealed increased bone marrow (BM) myelopoiesis in LIP mice. Consistently, BM transplantation from LIP mice transferred colitis susceptibility to naïve recipients, demonstrating that oral inflammation imprints memory in BM myeloid progenitors. Moreover, colonization by the oral pathobiont Klebsiella aerogenes was required to recall this memory in the gut and exacerbate colitis. To investigate mechanisms of recall specificity, we performed single-cell RNA sequencing of mononuclear phagocytes (MNPs) from a competitive BM transfer model. LIP-derived MNPs displayed upregulation of interferon (IFN)-responsive genes. Functionally, while monocytes from control and LIP-R mice responded similarly to LPS alone, IFN-γ priming selectively amplified LPS-induced pro-inflammatory cytokines in LIP-R monocytes. Importantly, gut colonization by K. aerogenes increased mucosal IFN-γ levels. Thus, pathobiont-induced IFN-γ appears essential for recalling oral inflammation-imprinted memory in the gut. Together, our findings reveal that oral inflammation imprints long-lasting innate immune memory in BM myeloid progenitors. This memory persists after resolution of oral disease and can be reactivated in the gut mucosa by IFN-γ-inducing pathobionts such as K. aerogenes. These results provide new mechanistic insights into the oral–gut axis in IBD pathogenesis.

Abstract Based on the known perturbations in microbiome composition and the efficacy of fecal microbial transplantation, microbiome therapies are promising new options for ulcerative colitis (UC). Bacterial consortia as therapeutics have not yet demonstrated effectiveness in UC. An oral microbiome therapeutic is an attractive option for treating mild to moderate UC as monotherapy and potentially in combination with other therapies across the spectrum of disease severity. While probiotics such as Escherichia coli Nissle 1917 (EcN) have marginal efficacy in treating acute flares, they have shown similar efficacy to 5-ASA therapy in remission maintenance. We hypothesized that probiotic and live biotherapeutic product (LBP) efficacy is limited because of failure to colonize the inflamed colon. This failure may be due to vulnerability to oxidative stress. To overcome this, we genetically engineered EcN to enhance colonization. We inserted the ttr operon from Salmonella enterica, which enables tetrathionate (TTR), a gut inflammation byproduct, to be an energy source, providing EcN with a selective advantage during inflammation. EcN::ttr is designed to replicate in response to the degree of underlying inflammation, based on TTR availability, providing a finely tuned therapeutic effect titrated to induce and maintain remission. In both DSS and Muc2-/- murine colitis models, EcN::ttr was significantly more effective in ameliorating colitis than both the unmodified parental strain and 5-ASA therapy. For clinical trials of EcN::ttr, we developed a proprietary oral microencapsulation formulation that optimizes colonic delivery to further enhance colonization. In a 7-day DSS porcine model of colitis, a single dose of orally administered EcN::ttr markedly reduced mortality, with untreated pigs having 20% mortality and severe illness, while treated animals resembled healthy controls clinically and histologically. EcN::ttr treatment preserved gut mucosal integrity and was well tolerated. Two dosing regimens were effective, with evidence of a dose-response for some parameters. This efficacy was achieved with modest doses that can be manufactured efficiently at low cost, providing compelling rationale to advance EcN::ttr as a next-generation microbiome therapeutic into human trials. EcN::ttr may be particularly effective in the maintenance of remission, where the parent EcN strain has previously shown some efficacy albeit in high dosing regimens. A phase 1 trial in 2026 will establish safety and tolerability, followed by an efficacy study initially focused on maintenance of remission and flare prevention in UC. We have shown that the addition of ttr enhances the efficacy of EcN’s anti-inflammatory effects resulting from successful colonization. EcN::ttr may be a novel therapy for UC due to its enhanced ability to successfully colonize the inflamed gut.

The purpose of this research was to investigate how adding dietary guar gum to high‐lipid diets affected the fish growth and gut health of common carp (Cyprinus carpio). A normal‐lipid diet (5% crude lipid; control) and four high‐lipid diets (10% crude lipid) with 0% (high‐fat [HF]), 0.3% (GG0.3), 1% (GG1), and 3% (GG3) of guar gum were developed and fed to fish (4.53 g) for 8 weeks. The findings showed that HF induced impairment of intestinal morphology and mucosal barrier, oxidative stress, gut dysbiosis, and gut inflammation. Compared to the HF, guar gum‐containing diets substantially improved gut villus height, upregulated the expression levels of nuclear factor erythroid 2-related factor 2 and zonula occludens-1, and downregulated the expression levels of toll-like receptor 1 (tlr1), tlr5, myeloid differentiation factor 88, interleukin-1β (il-1β), il-6, and il-8. Moreover, the GG0.3 and GG1 diets dramatically increased catalase (cat) and occludin expression levels. Furthermore, the GG1 and GG3 diets improved the microbiota composition by increasing Fusobacteria and Cetobacterium abundance while lowering Proteobacteria, Acidovorax, Acinetobacter, Serratia, and Comamonas abundance. Correlation analysis revealed that guar gum improved gut health by modulating gut microbiota and tight junction proteins. The findings indicated that guar gum can ameliorate HF diet‐induced intestinal damage in fish.

BackgroundPregnant individuals with inflammatory bowel diseases (IBD) exhibit gut inflammation and dysbiosis; however, there is limited knowledge about their vaginal environment. This is important as vaginal inflammation and high vaginal microbiota diversity are associated with adverse pregnancy outcomes.ObjectivesWe aimed to compare vaginal inflammatory markers and microbiota diversity of pregnant individuals with and without IBD in their third trimester of pregnancy and determine the role of diet in the vaginal microbiota diversity.MethodsWe recruited pregnant individuals who provided vaginal swabs at 27–29 weeks of pregnancy. We characterized the vaginal microbiota by sequencing the V3-V4 region of the 16S rRNA and surveyed nine key pro and anti-inflammatory cytokines by qRT-PCR from the vaginal mucosa. Participants completed three validated interviewer-led nutrition assessments of 24-hour dietary intake around the same time as the collection of vaginal samples. The nutritional assessments were used to estimate dietary quality using the validated Healthy Eating Index (HEI-2015).ResultsThe cohort included 23 pregnant individuals with IBD (18 with Crohn’s disease and 5 with ulcerative colitis) and 25 healthy controls (HC); 56.5% of the IBD cases were in remission. Vaginal microbiota diversity and composition did not differ significantly between individuals with IBD and HC. However, the vaginal mucosa of the IBD individuals showed increased expression of Th17 pro-inflammatory cytokines (i.e., IL-6, IL-8, IL-17) and decreased expression of Th1 (IFN-γ) and Th2 (IL-4) compared to HC. Expression of IL-6 and TNF- α correlated positively with vaginal microbial diversity. The beneficial Lactobacillus crispatus dominated the vaginal microbiota of individuals with either high dietary quality or those consuming more vegetables or low added sugar, regardless of IBD status. In IBD cases, consumption of vegetables and added sugars were associated with reduced expression of the pro-inflammatory IFN-γ and an increased expression of anti-inflammatory IL-4.ConclusionThe vaginal microbiome did not differ between individuals with IBD and HC; however, IBD cases exhibit a pro-inflammatory tone in the vagina (high IL-6) that is associated with higher vaginal microbial diversity. Regardless of IBD status, healthier diets are positively associated with an increased abundance of the beneficial L. crispatus in the vagina.

The diagnosis and monitoring of inflammatory bowel disease (IBD) relies on histologic and endoscopic analysis, as well as measurements of generic markers of inflammation. However, there are no specific tests that report on T cell-mediated immune responses as a key driver of IBD pathogenesis. Here we detect increasing granzyme A (GzmA) in gut biopsies and confirm that CD8+ T cells secrete its active form to induce interleukin (IL)-8. We then rationally design a non-invasive chemiluminescence assay for measuring active GzmA in stool supernatants from patients with IBD. For our assay, we synthesize peptide-based GzmA-specific inhibitors and chemiluminescent reporters and use them to characterize biosamples from ~150 human patients with IBD and healthy controls. Our results demonstrate that GzmA activity is an indicator of gut inflammation that can enhance the identification of patients with IBD over existing tests and potentially act as a mechanistic biomarker for the dominance of T cell activity. We envision that the selectivity and sensitivity of our GzmA activity-based optical assay will accelerate the design of additional biomedical approaches to enhance precision medicine in IBD.

BackgroundWhile immunoblobulin A(IgA) dominates gut mucosal immunity, the roles of immunoglobulin M (IgM) and immunoglobulin G (IgG) in host-microbiota interactions remain poorly characterized, particularly in schizophrenia (SCZ). Although gut dysbiosis and immune activation have been implicated in SCZ,the contribution of IgG/IgM-coated gut microbiota to disease associated inflammation and behavioral alterations remains unknown.MethodsWe recruited six patients with SCZ, six with other psychiatric disorders (OPD) and six age- and sex- matched healthy controls. IgG/IgM-coated gut microbiota were isolated from 100 mg fecal samples via magnetic-activated cell sorting (MACS) and profiled by 16S rRNA sequencing. A pilot an IgG/IgM-coated fecal microbiota transplantation (FMT) using anaerobically cultured human intestinal microbiota was conducted in mice to assess the effects on gut pathology, peripheral immunity, and behavior. The percentage of neutrophil granulocyte in peripheral blood was quantified microscopically, and statistical analyses were performed using one-way ANOVA in GraphPad Prism 8, with (p < 0.05.ResultsThe proportions of IgM-coated bacteria was significantly higher in patients with SCZ than in healthy controls (p<0.05), with enrichment of Rhodococcuss, Shigella, Clostridium and Streptococcus. Mice receiving a mixture of high-IgM-coated intestinal bacteria mixture showed reduced depletion of peripheral neutrophils, mild colon shortening, and mucosal inflammation compared with those receiving low IgM-coated or uncoated bacteria. In contrast, high IgG-coated bacteria, enriched in Rhodococcuss, Acinetobater and Pseudomonas, decreased in SCZ, but induced similar inflammatory gut changes. No IgG- nor IgM- induced anxiety-like behavior were detect in the mice.ConclusionsOur findings reveal that IgG/IgM-coated intestinal microbiota display distinct immunoreactive microbiota signatures associated with SCZ. These coated communities promote gut inflammation without inducing anxiety-like behavior, highlighting their potential as novel biomarkers of SCZ-associated immune dysregulation and as targets for personalized therapeutic strategies.

IntroductionIn early stage non-small cell lung cancer (NSCLC), recurrence is frequent despite surgery and systemic treatments. Observational studies suggest that physical exercise and nutrition could improve outcomes, such as survival and treatment tolerance; however, solid evidence is lacking. The STARLighT trial aims to assess the effects of a telehealth-delivered combined exercise and nutrition intervention on clinical, biological and patient-reported outcomes in early stage NSCLC.Methods and analysisSTARLighT is a multicentre master protocol study conducted in Italy, comprising two cohorts of patients affected by early stage NSCLC (stages IB–IIIA) epidermal growth factor receptor and anaplastic lymphoma kinase wild type. Cohort A will include 46 patients with resectable NSCLC receiving neoadjuvant treatment and will exploit a single-arm phase II design. Cohort B will enrol 268 patients undergoing adjuvant treatment (including as a part of a perioperative strategy) and proposes a randomised controlled phase III design. Patients in Cohort A and those allocated to the interventional arm in Cohort B will receive a tailored telehealth-delivered exercise and nutritional intervention. The control group will receive the usual care plus educational material. For cohort A, two coprimary endpoints are set: pathological complete response and quality of life, whereas the primary endpoint for cohort B is 2-year disease-free survival. Secondary and exploratory endpoints include a series of clinical (eg, overall survival and safety), biological (immune–inflammatory markers, gut microbiota and transcriptomics) and patient-reported outcomes (eg, sleep habits, physical activity, anxiety and depression and distress) evaluations.Ethics and disseminationThe study is approved by the Ethics Committee of the University of Verona (Prot. No. 33979) and registered on ClinicalTrials.gov (NCT07042724). Findings will be disseminated through peer-reviewed journals, scientific meetings, public forums and guideline updates.Trial registration numberClinicaltrial.gov: NCT07042724.

The intestinal epithelium relies on continuous stem cell-driven renewal to maintain barrier function and recover from injury. While bacterial signals are known to influence intestinal stem cell behaviour, the regenerative capacity of the gut mycobiome has remained largely unexplored. Here we identify the commensal fungus Kazachstania pintolopesii (Kp) as a critical mediator of intestinal regeneration through its secreted protein Ygp1. We found that a 12-amino acid peptide fragment of Ygp1, CD12, was sufficient to promote intestinal organoid differentiation and accelerate intestinal healing in murine models of colitis and chemotherapy-induced injury. Transcriptomics, simulations and molecular interaction experiments revealed that CD12 binds mammalian α-enolase (ENO1), enhancing YAP1 (Yes-associated protein 1) protein levels and activating regenerative transcriptional programmes through the Hippo signalling pathway. Engineered probiotics expressing CD12 replicated its therapeutic benefits, offering a translatable delivery strategy. Our work expands the therapeutic potential of the mycobiome, positioning it as a source of biologics for inflammatory and iatrogenic gut disorders.

Chronic stress, gut dysbiosis, and cholesterol metabolism: Implications for Alzheimer's disease.

The IL17REL gene locus has been associated with susceptibility to inflammatory bowel disease (IBD). However, whether it encodes a functional protein and whether its IBD risk variants causally contribute to disease pathogenesis remain unknown. Here, we demonstrated that IL17REL encodes a decoy receptor capable of binding interleukin-17 (IL-17) family cytokines and suppressing intestinal inflammation. By contrast, proteins encoded by IBD-associated IL17REL variants lacked this function. We also showed that TGFβ1 induced IL17REL transcription, and its expression positively correlated with TGFB1 levels in IBD. Mechanistically, the IL-17REL protein competed with IL-17RA for IL-17A binding, an ability that is lost in the mutant form. Knock-in of IL17REL in mice alleviated 2,4,6-trinitrobenzene sulfonic acid-induced colitis, whereas knock-in of an IBD-associated IL17REL mutant did not. In addition, therapeutic administration of IL-17REL protein alleviated colitis symptoms. Together, these findings implicate IL-17REL variants in the pathogenesis of IBD and highlight IL-17REL as a potential therapeutic target.

HighlightsWhat are the main findings?Ultrasonicated Enterococcus faecium F11.1G effectively alleviates the LPS-induced inflammatory damage in intestinal epithelial cells.108 CFU/mL F11.1G significantly suppresses the excessive secretion of pro-inflammatory factors (IL-6, IL-8, IL-1β, and TNF-α).The anti-inflammatory mechanism of F11.1G primarily involves inhibiting the activation of the NF-κB/MAPK signaling pathways and may synergistically regulate the purine/endocannabinoid metabolic networks.What are the implications of the main findings?These findings provide experimental evidence supporting the potential of ultrasonicated Enterococcus faecium F11.1G as a postbiotic agent for alleviating intestinal inflammation.The study suggests that F11.1G exerts its anti-inflammatory effects through multi-target modulation of inflammatory signaling pathways and metabolic networks.Lipopolysaccharide (LPS)-induced damage to the intestinal epithelial barrier leads to gut inflammation, and intracellular metabolites of lactic acid bacteria may participate in regulating this process to exert probiotic effects. This study aimed to investigate the repair effects and molecular mechanisms of ultrasonic disruption-treated Enterococcus faecium F11.1G (F11.1G) on the model (primary lamb IECs + 5 μg/mL LPS for 6 h). Then, results demonstrated that 108 CFU/mL F11.1G significantly suppressed the excessive secretion of pro-inflammatory factors (IL-6, IL-8, IL-1β, TNF-α) induced by LPS. Gene Ontology (GO) analysis revealed that differentially expressed genes (DEGs) were primarily enriched in cellular response to lipopolysaccharide, inflammatory response, and canonical NF-κB signaling pathways. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed enrichment in NF-κB signaling pathway and MAPK signaling pathway. PPI network identified key genes including IL-1β, TNF, IL-8, RELB, FOS, TNFAIP3, NFKBIA, and MMP9. KEGG analysis indicated differentially abundant metabolites (DAMs) enrichment in purine metabolism and the endocannabinoid system. Spearman correlation analysis revealed positive correlations between pro-inflammatory genes and endogenous protective metabolites, such as adenosine and PEA, while showing negative correlations with multiple purine metabolites. Correlational analysis indicates that F11.1G alleviates intestinal inflammatory damage primarily by suppressing NF-κB/MAPK pathway activation and may synergistically regulate purine and endocannabinoid metabolism.

Background: High-fat or high-fructose consumption may cause abnormal lipid accumulation in the liver, resulting in fatty liver disease, and the intervention of other stress factors may accelerate the progression of this condition. Many studies have demonstrated that long-term exposure to blue light may not only injure the eyes but also cause an increase in oxidative stress, which has been related to metabolic and gut microbiota disorders. However, current research on whether blue light exposure exacerbates fatty liver disease still remains limited. Objective: Therefore, the aim of this study is to investigate the effect of a high-fat, high-fructose diet combined with blue light exposure on fatty liver disease progression. Method: In the first part of the study, we observed that 16 weeks of blue light exposure alone did not achieve significant effects in the liver of male, female, or OVX mice. Therefore, in the second part, we fed ICR mice a high-fat, high-fructose (HFHF) diet to investigate the effect of simultaneous 16-week exposure to blue light. The mice were assigned to three groups, control group (C), HFHF diet group (H), and HFHF diet plus blue light exposure group (HB), to investigate the intervention of unhealthy diet composition and blue light exposure on hepatic oxidative and inflammatory makers and gut microbiota composition. Results: The results showed that exposure to blue light exacerbates oxidative stress (hepatic MDA, p < 0.009), and inflammatory damage (lobular inflammation score, p < 0.0001; hepatic TNF-α, p = 0.0074) caused by an HFHF diet, but this mechanism is not mediated by the TLR4 signaling pathway. Furthermore, exposure to blue light may also partially affect the composition of the gut microbiota. Conclusions: The results of the study suggested that under unhealthy dietary conditions, long-term blue light exposure may be one of the risk factors accelerating the progression of fatty liver disease.

Shifting to a plant-based diet naturally alters protein source choices. In many countries, protein from yellow pea is widely used as a main ingredient in meat alternatives. Still, its biological effects, especially regarding gastrointestinal health, remain incompletely understood. The aim of our study was to investigate how a weekly increase in the intake of a well-characterized pea protein isolate affects surrogate markers of health, fecal short-chain fatty acids and gut microbiota composition in healthy individuals. Male and female adults (N = 29) participated in this exploratory intervention study. A 4-week pre-intervention period for questionnaires and fecal samples collection was followed by a 4-week supplementation. Participants consumed isolated pea protein in weekly increasing amounts, starting from 0.25 g per kg body mass per day in week 5 to 1.00 g per kg body mass per day in week 8. Questionnaire data, fecal samples as well as fasting blood and 24 h urine samples were collected weekly. Data from biological samples and questionnaires confirmed a healthy study population and compliance. Fecal calprotectin levels significantly increased only in a subset of participants, which was accompanied by higher fecal water cytotoxicity in vitro. Short-chain fatty acids mainly rose in those subjects with stable calprotectin levels. Relative abundances of Limosilactobacillus frumenti, Odoribacter splanchnicus and Lactobacillus crispatus increased significantly in the total population during the intervention while the relative abundance of Bifidobacterium longum and Bifidobacterium catenulatum decreased. Our results indicate that an increased intake of pea protein isolate affects the growth of certain beneficial bacterial strains and differentially influences markers related to gut inflammation in healthy individuals.

The exopolysaccharide SREP-1, purified from the fermentation broth of Stropharia rugosoannulata, exhibited antiaging potential. As aging significantly alters gut structure and function, protective effect of SREP-1 was investigated using a d-galactose-induced aging mouse model. SREP-1 administration reversed D-galactose-induced body weight loss and colon damage, as evidenced by improved histopathology. SREP-1 mitigated weight loss and colon damage, enhanced the activities of antioxidants (SOD, GSH-Px, and CAT), and reduced the level of MDA. It decreased proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and elevated IL-10 in colon tissue, while boosting serum immunoglobulins (IgG and IgM). Crucially, these effects were abolished by antibiotic pretreatment, highlighting the role of gut microbiota in SREP-1 bioactivity. This role was further confirmed through fecal microbiota transplantation (FMT) and fecal supernatant transplantation (FST) experiments. Based on 16S rRNA sequencing, SREP-1 restored gut microbial diversity, increased beneficial genera (e.g., Faecalibacterium, Akkermansia, Lactobacillus, and Bacteroides), and decreased harmful bacteria (e.g., Escherichia-Shigella and Collinsella). Furthermore, short-chain fatty acids (SCFAs) levels were elevated in the SREP-1 group, which might regulate GPCRs/NF-κB/Nrf2 signaling pathways and exert biological activity. This study revealed the potential of SREP-1 to alleviate aging-related intestinal dysfunction and underscored the crucial role of gut microbiota in mediating these effects.

Flavonoids are one of the bioactive compounds among polyphenols that are found in fruits and vegetables. The flavonoids mostly get metabolized in the alimentary canal, and their interaction with the gut microbiome becomes inevitable. The gut microbiota continuously interacts with dietary flavonoids and catabolizes them into more minor metabolites directly associated with the host health. The gut microbiota is resilient and highly dependent on environmental entities, such as xenobiotics, antibiotics, and diet patterns. Any abrupt alterations in these exogenous entities cause gut dysbiosis, resulting in different abnormalities and disorders. The flavonoids alter the proportion of Firmicutes to Bacteroidetes in the gut, and those bacteria play a decisive role in the host physiology. This review draws attention to how flavonoids ameliorate gut dysbiosis and inflammation. Additionally, the biomarkers and cell signaling before and after the onset of gut dysbiosis have been discussed. Ultimately, we emphasize how flavonoid-mediated gut microbiome ameliorates intestinal-related metabolic conditions such as obesity, Crohn's disease (CD), and intestinal ulcerative colitis (IUC). In the future, further studies on the clinical level and model-based studies will warrant the use of flavonoids as better therapeutics and understanding of host health correlated with the microbiome.