Irritable Bowel Syndrome (IBS) is a functional gastrointestinal disorder characterized by abdominal pain associated with changes in stool consistency or bowel movement frequency. It is a highly prevalent chronic relapsing disorder that substantially impairs patients’ quality of life and elevates societal healthcare costs. The low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet has emerged as a cornerstone dietary intervention for IBS owing to its demonstrated efficacy in alleviating symptoms. This article systematically reviews the progress in understanding the mechanism of the low FODMAP diet in the treatment of IBS, covering key dimensions such as reduced intestinal gas production, osmotic regulation, gut microbiota balance, abnormal intestinal fermentation, intestinal inflammatory and immune activation, and improvement in the gut-brain axis function. Additionally, this article reviews predictors of treatment response and outlines future research priorities based on recent evidence.

BackgroundGut dysbiosis is hypothesized to be a potential pathological mechanism in patients across the Alzheimer’s disease (AD) spectrum. Nevertheless, despite growing interest, existing findings remain largely inconsistent.PurposeThis systematic review and meta-analysis aimed to compare the composition of gut microbiota (GM) between patients with mild cognitive impairment (MCI) or AD and healthy controls (HC).MethodsPubMed, Embase, MEDLINE and Web of science were searched from January 2022 to November 2025. Eligible studies included observational studies and pre-intervention arms of interventional trials reporting GM abundance in AD spectrum patients vs. HC. Two reviewers independently screened articles, extracted data, and assessed bias risk. Effect sizes were pooled using an inverse-variance weighted random-effects model.ResultsTwenty studies (1,025 HC and 456 AD spectrum patients) were analyzed. AD patients demonstrated reduced GM diversity vs. HC cohort. The abundances of Megamonas and Bacteroides were elevated in AD patients, while Firmicutes and Proteobacteria were reduced. When stratified by clinical stage, Fusobacteria and Lactobacillus abundances showed gradient shift from MCI to AD.ConclusionIndividuals within the AD spectrum exhibit altered GM abundance, with these differences influenced by clinical stage. The present study did not identify any significant trends; it reports only findings that have been statistically substantiated.

INTRODUCTION:Long-term studies characterizing the natural history of functional bowel disorder (FBD) from community-based settings and exploring association with psychological factors are sparse. We aimed to evaluate the evolution of symptoms, health outcomes, and association of FBD with psychological disorders in Chinese population. METHODS:Individuals identified from random sampling of residents of Hangzhou, China, participated in a baseline survey in January 2010. Follow-up phone survey was conducted in December 2018. FBD was diagnosed based on Rome III criteria. RESULTS:Among 452 individuals (mean age 44.6 ± 15.3 years, 174 [38%] male) who completed the study, the prevalence of FBD was 36.3% (95% confidence interval [CI] 32.6-40.0%) at enrollment and 36.1% (95% CI 32.3-39.8%) at follow-up survey ( P = 0.94). However, 214 individuals (47%) had interval change in diagnosis. Although no difference in incidence of organic disease or death was observed, a higher proportion of patients with FBD (16/164, 9.8% vs 9/288, 3.1%; P = 0.003) compared with those without FBD received non-cancer-related abdominal and/or pelvic surgery during follow-up. FBD was associated with anxiety and/or depression at initial (adjusted odds ratio [AOR] = 1.7, 95% CI 1.7-2.7, P = 0.02) and follow-up (AOR = 8.0, 95% CI 3.2-20.0, P < 0.001) surveys. Diagnosis of FBD at baseline was associated with new-onset anxiety and/or depression at follow-up (AOR = 3.2, 95% CI 1.2-8.3, P = 0.01). DISCUSSION:Although the prevalence of FBD remained stable, transformation of symptoms was common over time. Patients with FBD may have increased risk of receiving non-cancer-related abdominal and/or pelvic surgery. FBD symptoms at baseline increased the risk of new-onset anxiety and/or depression by 3.2-fold over the next 9 years.

Declined numbers and weakened functions of intestinal stem cells (ISCs) impair the integrity of the intestinal epithelium during aging. However, the impact of intestinal microbiota on ISCs in this process is unclear. Here, using premature aging mice (telomerase RNA component knockout, Terc-/-), natural aging mice, and in vitro colonoid models, we explore how heat-inactivated Bifidobacterium adolescentis (B. adolescentis) affects colon senescence. We find that B. adolescentis could mitigate colonic senescence-related changes by enhancing intestinal integrity and stimulating the regeneration of Lgr5+ ISCs via Wnt/β-catenin signaling. Furthermore, we uncover the involvement of Paneth-like cells (PLCs) within the colonic stem-cell-supporting niche in the B. adolescentis-induced ISC regeneration. In addition, we identify soluble polysaccharides (SPS) as potential effective components of B. adolescentis. Overall, our findings reveal the role of heat-inactivated B. adolescentis in maintaining the ISCs regeneration and intestinal barrier, and propose a microbiota target for ameliorating colon senescence.

衰老是指年龄增长伴随的机体结构和功能衰退.由于预期寿命的延长,出生率的下降,老年人群比例不断增加.不断加重的老龄化及其带来的健康和社会经济问题已经受到了广泛的关注.老年综合征(geriatric syndrome,GS)和衰弱症已被应用于老年人群的健康状况评估.但是,目前临床上仍缺乏针对一般人群的系统衰老评估手段,忽视衰老与各种疾病的密切联系.这不仅不能从整体视角对老年人进行共病管理,更与"治未病"的公共健康策略背道而驰.前期的基础和临床研究已经初步确定了衰老的相关表现及其机制,并发展了饮食、药物等干预衰老的手段.本文将综述关于衰老的研究进展,对衰老的机制、评估和干预进行详细的分类阐述,并提出老化综合征(senescence syn-drome,SS)这一概念,主张从整体的预防的角度关注老年群体的健康.

Proton pump inhibitors (PPIs) are the mainstay of therapy for gastroesophageal reflux disease (GERD) but up to 60% of patients have inadequate response to therapy. Acid sensing ion channels (ASICs) play important roles in nociception. This study aimed to investigate whether the increased expression of ASICs results in neuronal hyperexcitability in GERD. Esophageal biopsies were taken from GERD patients and healthy subjects to compare expression of ASIC1 and 3. Next, gene and protein expression of ASIC1 and 3 from esophageal mucosa and dorsal root ganglia (DRG) neurons were measured by qPCR, Western-blot and immunofluorescence in rodent models of reflux esophagitis (RE), non-erosive reflux disease (NERD), and sham operated groups. Excitability of DRG neurons in the GERD and sham groups were also tested by whole-cell patch-clamp recordings. We demonstrated that ASIC1 and 3 expression were significantly increased in patients with RE compared with healthy controls. This correlated positively with symptom severity of heartburn and regurgitation (p < .001). Next, ASIC1 and 3 gene and protein expression in rodent models of RE and NERD were similarly increased in esophageal mucosa as well as T3-T5 DRG neurons compared with sham operation. DRG neurons from RE animals showed hyperexcitability compared with sham group. However, intrathecal injection of ASIC specific inhibitors, PcTx1 and APTEx-2, as well as silencing ASIC1 and 3 genes with specific siRNAs prevented visceral hypersensitivity. Overall, upregulation of ASIC1 and 3 may lead to visceral hypersensitivity in RE and NERD and may be a potential therapeutic target for PPI non-responsive patients.

N-6-Methyladenosine (m6A) modification is involved in multiple biological processes including aging. However, the regulation of m6A methyltransferase-like 14 (METTL14) in aging remains unclear. Here, we revealed that the level of m6A modification and the expression of METTL14 were particularly decreased in the intestine of aged mice as compared to young mice. Similar results were confirmed in Drosophila melanogaster. Knockdown of Mettl14 in Drosophila resulted in a short lifespan, associated disrupted intestinal integrity, and reduced climbing ability. In human CCD-18Co cells, knockdown of METTL14 accelerated cellular senescence, and the overexpression of METTL14 rescued senescent phenotypes. We also identified the lamin B receptor (LBR) as a target gene for METTL14-mediated m6A modification. Knockdown of METTL14 decreased m6A level of LBR, resulted in LBR mRNA instability, and thus induced cellular senescence. Our findings suggest that METTL14 plays an essential role in the m6A modification-dependent aging process via the regulation of LBR and provides a potential target for cellular senescence.

Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) are carbohydrates thought to contribute to the symptoms of IBS. A diet in high in FODMAPs (HFM) induces gastrointestinal symptoms in patients with irritable bowel syndrome (IBS), and a diet low in FODMAPs (LFM) improves symptoms in up to 60% of patients with IBS. However, the mechanism by which FODMAPs affect IBS symptoms is unclear. We showed that mice fed on a HFM diet have mast cell activation and colonic barrier loss. Using mast cell-deficient mice with and without mast cell reconstitution, we showed that HFM-mediated colonic barrier loss is dependent on TLR4-dependent mast cell activation. In in vitro studies, we demonstrated that IBS fecal supernatant stimulates mast cells significantly more compared with fecal supernatant from healthy controls. This effect of IBS fecal supernatant on mast cell stimulation is ameliorated in the absence of the TLR4 receptor and after a LFM diet. We found that a LFM diet improves colonic barrier function and reduces mast cell activation while decreasing fecal LPS levels. Our findings indicate that a HFM diet causes mast cell activation via LPS, which in turn leads to colonic barrier loss, and a LFM diet reverses these pathophysiologic mucosal changes.

INTRODUCTION: The prevalence and shedding of fecal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA indicate coronavirus disease 2019 (COVID-19) infection in the gastrointestinal (GI) tract and likely infectivity. We performed a systemic review and meta-analysis to evaluate the prevalence and the duration of shedding of fecal RNA in patients with COVID-19 infection. METHODS: PubMed, Embase, Web of Science, and Chinese databases Chinese National Knowledge Infrastructure and Wanfang Data up to June 2020 were searched for studies evaluating fecal SARS-CoV-2 RNA, including anal and rectal samples, in patients with confirmed COVID-19 infection. The pooled prevalence of fecal RNA in patients with detectable respiratory RNA was estimated. The days of shedding and days to loss of fecal and respiratory RNA from presentation were compared. RESULTS: Thirty-five studies (N = 1,636) met criteria. The pooled prevalence of fecal RNA in COVID-19 patients was 43% (95% confidence interval [CI] 34%–52%). Higher proportion of patients with GI symptoms (52.4% vs 25.9%, odds ratio = 2.4, 95% CI 1.2–4.7) compared with no GI symptoms, specifically diarrhea (51.6% vs 24.0%, odds ratio = 3.0, 95% CI 1.9–4.8), had detectable fecal RNA. After loss of respiratory RNA, 27% (95% CI 15%–44%) of the patients had persistent shedding of fecal RNA. Days of RNA shedding in the feces were longer than respiratory samples (21.8 vs 14.7 days, mean difference = 7.1 days, 95% CI 1.2–13.0). Furthermore, days to loss of fecal RNA lagged respiratory RNA by a mean of 4.8 days (95% CI 2.2–7.5). DISCUSSION: Fecal SARS-CoV-2 RNA is commonly detected in COVID-19 patients with a 3-fold increased risk with diarrhea. Shedding of fecal RNA lasted more than 3 weeks after presentation and a week after last detectable respiratory RNA.

Abstract Background and Aim: Chronic atrophic gastritis is a common gastric disease which shows a positive correlation with the occurrence of gastric cancer. Traditional chinese medicines have been used in the treatment of chronic atrophic gastritis. There is no solid evidence for the curative effects of traditional chinese medicines. This study aimed to investigate the clinical efficacy of Weifuchun tablets on patients with chronic atrophic gastritis. Methods 97 patients of chronic atrophic gastritis without current H. pylori infection were divided into two groups: an experiment group treated with Weifuchun and a control group treated with teprenone and folic acid for six months. Pathological examination of gastric biopsies and clinical symptoms assessment were performed for all patients before and after treatments. Primary outcome was the pathological response rate in each group evaluated by changes of histological scores.Secondary outcome was the clinical symptom scores. Results Twenty four patients in the Weifuchun group and twenty eight patients in the control group completed the study. The pathological response rates for atrophy and intestinal metaplasia were 66.7% and 45.8% in the Weifuchun group and 66.7% and 42.9% in the folic acid group, respectively, without statistical significance between groups.Clinical symptoms failed to improve after treatments in either group. Conclusions Weifuchun is effective to improve pathological changes of chronic atrophic gastritis in patients without current H. pylori infection. Monotherapy of Weifuchun had a similar efficacy to the combined therapy by teprenone and folic acid in the treatment of chronic atrophic gastritis. Trial registration: Evaluation of Weifuchun Pills on chronic atrophic gastritis, ChiCTR-IPR-17013939, Registered 15 December 2017, http://www.chictr.org.cn/ showproj.aspx?proj = 23910.

To identify candidate bacteria associated with aging, we performed fecal microbiota sequencing in young, middle-aged and older adults, and found lower Bifidobacterium adolescentis abundance in older individuals aged ≥60 years. Dietary supplementation of B. adolescentis improved osteoporosis and neurodegeneration in a mouse model of premature aging (Terc −/− ) and increased healthspan and lifespan in Drosophila melanogaster and Caenorhabditis elegans . B. adolescentis supplementation increased the activity of the catalase (CAT) enzyme in skeletal muscle and brain tissue from Terc −/− mice, and suppressed cellular senescence in mouse embryonic fibroblasts. Transgenic deletion of catalase ( ctl-2 ) in C. elegans abolished the effects of B. adolescentis on the lifespan and healthspan. B. adolescentis feeding also led to changes in oxidative stress-associated metabolites in Terc −/− mouse feces. These results suggest a role for B. adolescentis in improving the healthspan and lifespan through the regulation of CAT activity and host metabolism.

BACKGROUNDThe efficacy and factors associated with patient outcomes for a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (LFD) compared with traditional dietary advice (TDA) based on modified National Institute for Clinical Excellence guidelines for irritable bowel syndrome with diarrhea (IBS-D) in regions consuming a non-Western diet are unclear.OBJECTIVESWe aimed to determine the efficacy of an LFD compared with TDA for the treatment of IBS-D in Chinese patients and to investigate the factors associated with favorable outcomes.METHODSOne hundred and eight Chinese IBS-D patients (Rome III criteria) were randomly assigned to an LFD or TDA. The primary endpoint was a ≥50-point reduction in the IBS Severity Scoring System at 3 wk. Fecal samples collected before and after the dietary intervention were assessed for changes in SCFAs and microbiota profiles. A logistic regression model was used to identify predictors of outcomes.RESULTSAmong the 100 patients who completed the study, the primary endpoint was met in a similar number of LFD (30 of 51, 59%) and TDA (26 of 49, 53%) patients (∆6%; 95% CI: -13%, 24%). Patients in the LFD group achieved earlier symptomatic improvement in stool frequency and excessive wind than those following TDA. LFD reduced carbohydrate-fermenting bacteria such as Bifidobacterium and Bacteroides, and decreased saccharolytic fermentation activity. This was associated with symptomatic improvement in the responders. High saccharolytic fermentation activity at baseline was associated with a higher symptom burden (P = 0.01) and a favorable therapeutic response to the LFD (log OR: 4.9; 95% CI: -0.1, 9.9; P = 0.05).CONCLUSIONSAn LFD and TDA each reduced symptoms in Chinese IBS-D patients; however, the LFD achieved earlier symptomatic improvements in stool frequency and excessive wind. The therapeutic effect of the LFD was associated with changes in the fecal microbiota and the fecal fermentation index. At baseline, the presence of severe symptoms and microbial metabolic dysbiosis characterized by high saccharolytic capability predicted favorable outcomes to LFD intervention.This trial was registered at clinicaltrials.gov as NCT03304041.

in mice treated with WAS, WAS and MSG (23.5mg in gavage/day for 5 days) and controls were measured via afferent recordings.Jejunal afferents from WAS-treated mice responded significantly more (24%) at pressures between 40 and 60 mmHg when MSG was applied intraluminally (p<0.01).Similarly, jejunal afferents from mice treated with WAS and MSG gavage responded significantly more; however, at pressures between 10 and 60 mmHg in the presence of MSG (p<0.05)(Figure 1).No significant difference in response was observed in control mice.Based on single-unit analysis of afferent nerve recordings from mice treated with WAS and MSG in vivo, the firing frequencies of high-threshold units (units that respond at pressures greater than 15 mmHg) were significantly increased in the presence of MSG during distension (p<0.05) ( Figure 2).Ussing chamber permeability assays established that WAS-treated jejunum was significantly more permeable to 10 mM MSG (p<0.05) in comparison to control.With this, we decided to apply 10 µM MSG directly to control jejunal preparations; allowing the MSG to directly access visceral afferent nerve terminals without having to traverse the mucosa and observed an increase in distension response specifically at 60 mmHg (25%; p<0.01).These findings demonstrate that in vivo administration of MSG increases visceral sensitivity in a pre-clinical model for IBS.This increase in visceral sensitivity is driven by an increase in high-threshold unit activity and may be attributable to changes in mucosal permeability.

Human intestinal microbiota is affected by the exogenous microenvironment. This study aimed to determine the effects of cigarettes and alcohol on the gut microbiota of healthy men. In total, 116 healthy male subjects were enrolled and divided into four groups: non-smoking and non-drinking (Group A), smoking only (Group B), drinking only (Group C), and smoking and drinking combined (Group D). Fecal samples were collected and sequenced using 16S rRNA to analyze the microbial composition. Short-chain fatty acid (SCFAs) levels in feces were determined by gas chromatography. We found that cigarette and alcohol consumptions can alter overall composition of gut microbiota in healthy men. The relative abundances of phylum Bacteroidetes and Firmicutes and more than 40 genera were changed with cigarette and alcohol consumptions. SCFAs decreased with smoking and alcohol consumption. Multivariate analysis indicated that when compared with group A, group B/C/D had higher Bacteroides , and lower Phascolarctobacterium, Ruminococcaceae_UCG-002, Ruminococcaceae_UCG-003 , and Ruminiclostridium_9 regardless of BMI and age. Additionally, the abundance of Bacteroides was positively correlated with the smoking pack-year (r = 0.207, p < 0.05), the abundance of predicted pathway of bacterial toxins (r = 0.3672, p < 0.001) and the level of carcinoembryonic antigen in host (r = 0.318, p < 0.01). Group D shared similar microbial construction with group B, but exerted differences far from group C with lower abundance of Haemophilus . These results demonstrated that cigarette and alcohol consumption separately affected the intestinal microbiota and function in healthy men; furthermore, the co-occurrence of cigarette and alcohol didn’t exacerbate the dysbiosis and cigarette played the predominated role on the alteration.

INTRODUCTION: A diet high in FODMAPs (HFM) induces symptoms in patients with irritable bowel syndrome (IBS) and a diet low in FODMAPs (LFM) improves symptoms in up to 60% of IBS patients. Studies report increased colonic mast cell abundance and activation in a subset of IBS patients. However, the role of mast cells in pathophysiology of FODMAPs related symptom-generation has not been well studied. METHODS: C57Bl/6 mice and mast cell deficient W-sash c-kit mutant (KitW/W-v) mice were randomized to HFM or regular chow (RC) daily for 2 weeks. Ex vivo and in vivo epithelial barrier function was assessed using trans-epithelial electrical resistance (TEER), and plasma measurement of 4-kDa fluorescein isothiocynate (4-kDa-FITC–dextran) 1-hour after oral gavage. In addition, gene expression of tight junction proteins and inflammatory cytokines were measured. We also measured serum markers of mast cell activation in diarrhea-predominant IBS (IBS-D) patients after LFM. Statistical analysis was performed using t-test and P < 0.05 was considered significant. RESULTS: Wild-type mice (n = 8/group) fed on HFM had 18% reduction in TEER compared to those fed on RC (25.7 Ω.cm2 vs. 31.4 Ω.cm2, P = 0.04) as well as 5-fold increase plasma 4-kDa-FITC–dextran (30.8 µg/ml vs. 6.2 µg/ml, P = 0.04). In addition, HFM-fed rats had 24% reduction in colonic gene expression of occludin and 37% reduction in ZO-1 (P < 0.05 for both) compared to RC group. KitW/W-v mast-cell deficient mice (n = 4/group) fed on HFM did not have any significant changes in TEER measurement, plasma 4-kDa-FITC–dextran concentration and colonic expression of tight junction proteins compared to KitW/W-v mice fed on RC. Furthermore, there was 2-fold increase in gene expression of IFN-γ in wild-type mice fed on HFM compared to those fed on RC (P = 0.04). This increase in IFN-γ gene expression was also not seen in KitW/W-v mast-cell deficient mice fed on HFM compared to mast-cell deficient mice fed on RC. There was no difference in gene expression of TNF-α and IL-1β in wild type mice or mast-cell deficient mice groups. Consistent with this, we also found significant decrease in levels of markers of mast cell activation- serum histamine (P = 0.026) and tryptase (P = 0.034) in eight IBS-D patients after 4 weeks of LFM. CONCLUSION: HFM causes colonic epithelial barrier impairment and mucosal inflammation in wild-type mice but these changes are absent in mast-cell deficient mice. Mast cells play a critical role in HFM-induced colonic epithelial barrier dysfunction and inflammation.

Microbiota-host interaction was involved in aging, while the specific bacterium was undetermined. To identify candidate bacterium with aging, we performed fecal microbiota sequencing. Less richness of gut microbial community, and a reduction of B.adolescentis abundance was observed in elderly individuals. B. adolescentis supplement improved osteoporosis and neurodegeneration in telomerase RNA component deletion (Terc−/−) aged mice. B.adolescentis induced prolongevity and healthspan improvement in Drosophila melanogaster and C. elegans. Transgenic deletion of ctl-2 in C. elegans abolished the effect on lifespan and healthspan by B. adolescentis. The catalase activity was decreased in skeletal muscle and brain tissues of Terc−/− mice, as well as cellular senescence in mouse embryonic fibroblasts. B. adolescentis alleviated ROS accumulation by regulation of oxidative stress-associated metabolites. These results suggest a role for B. adolescentis in improving lifespan and healthspan by regulating catalase activity and host metabolism. Supplement with commensal bacteria is a promising strategy against age related diseases.