This editorial,inspired by a recent study published in the World Journal of Gastrointestinal Oncology,covers the research findings on microbiota changes in various diseases.In recurrent colorectal polyps,the abundances of Klebsiella,Parvimonas,and Clostridium increase,while those of Bifidobacterium and Lactoba-cillus decrease.This dysbiosis may promote the formation and recurrence of polyps.Similar microbial changes have also been observed in colorectal cancer,inflammatory bowel disease,autism spectrum disorder,and metabolic syndrome,indicating the role of increased pathogens and decreased probiotics in these conditions.Regulating the gut microbiota,particularly by increasing probiotic levels,may help prevent polyp recurrence and promote gut health.This microbial intervention strategy holds promise as an adjunctive treatment for patients with colorectal polyps.
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 pro-biotics may ameliorate these adverse effects.We focused on the bowel prepa-ration-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.
Gut dysbiosis,a phenomenon in which the existing commensal microbiome cha-nges to an adverse microenvironment in the colon,is thought to lead to altered cellular signals.How this is involved in producing mucosal outgrowths such as polyps in the colon is intriguing.Deciphering the various mechanisms involved provides an in-depth understanding of the link between gut dysbiosis and colonic polyps.
BACKGROUND Colorectal polyps,which are characterized by a high recurrence rate,represent preneoplastic conditions of the intestine.Due to unclear mechanisms of pathogenesis,first-line therapies for non-hereditary recurrent colorectal polyps are limited to endoscopic resection.Although recent studies suggest a mechanistic link between intestinal dysbiosis and polyps,the exact compositions and roles of bacteria in the mucosa around the lesions,rather than feces,remain unsettled.AIM To clarify the composition and diversity of bacteria in the mucosa surrounding or 10 cm distal to recurrent intestinal polyps.METHODS Mucosal samples were collected from four patients consistently with adenomatous polyps(Ade),seven consistently with non-Ade(Pol),ten with current Pol but previous Ade,and six healthy individuals,and bacterial patterns were evaluated by 16S rDNA sequencing.Linear discriminant analysis and Student’s t-tests were used to identify the genus-level bacteria differences between groups with different colorectal polyp phenotypes.Pearson’s correlation coefficients were used to evaluate the correlation between intestinal bacteria at the genus level and clinical indicators.RESULTS The results confirmed a decreased level of probiotics and an enrichment of pathogenic bacteria in patients with all types of polyps compared to healthy individuals.These changes were not restricted to the mucosa within 0.5 cm adjacent to the polyps,but also existed in histologically normal tissue 10 cm distal from the lesions.Significant differences in bacterial diversity were observed in the mucosa from individuals with normal conditions,Pol,and Ade.Increased abundance of Gram-negative bacteria,including Klebsiella,Plesiomonas,and Cronobacter,was observed in Pol group and Ade group,suggesting that resistance to antibiotics may be one risk factor for bacterium-related harmful environment.Meanwhile,age and gender were linked to bacteria changes,indicating the potential involvement of sex hormones.CONCLUSION These preliminary results suppo
Hyperuricemia(HUA)is a condition associated with a high concentration of uric acid(UA)in the bloodstream and can cause gout and chronic kidney disease.The gut microbiota of patients with gout and HUA is significantly altered compared to that of healthy people.This article focused on the complex interconnection between alterations in the gut microbiota and the development of this disorder.Some studies have suggested that changes in the composition,diversity,and activity of microbes play a key role in establishing and progressing HUA and gout pathogenesis.Therefore,we discussed how the gut microbiota contributes to HUA through purine metabolism,UA excretion,and intestinal inflammatory responses.We examined specific changes in the composition of the gut microbiota associated with gout and HUA,highlighting key bacterial taxa and the metabolic pathways involved.Additionally,we discussed the effect of conventional gout treatments on the gut microbiota composition,along with emerging therapeutic approaches that target the gut microbiome,such as the use of probiotics and prebiotics.We also provided insights into a study regarding the gut microbiota as a possible novel therapeutic intervention for gout treatment and dysbiosis-related diagnosis.
Abhay Kumar SinghSiva Sundara Kumar DurairajanAshok IyaswamyLeonard L Williams
Scavenger receptor class B,member 2(SCARB2)is linked to Gaucher disease and Parkinson’s disease.Deficiency in the SCARB2 gene causes progressive myoclonus epilepsy(PME),a rare group of inherited neurodegenerative diseases characterized by myoclonus.We found that Scarb2 deficiency in mice leads to age-dependent dietary lipid malabsorption,accompanied with vitamin E deficiency.Our investigation revealed that Scarb2 deficiency is associated with gut dysbiosis and an altered bile acid pool,leading to hyperactivation of FXR in intestine.Hyperactivation of FXR impairs epithelium renewal and lipid absorption.Patients with SCARB2 mutations have a severe reduction in their vitamin E levels and cannot absorb dietary vitamin E.Finally,inhibiting FXR or supplementing vitamin E ameliorates the neuromotor impairment and neuropathy in Scarb2 knockout mice.These data indicate that gastrointestinal dysfunction is associated with SCARB2 deficiency-related neurodegeneration,and SCARB2-associated neurodegeneration can be improved by addressing the nutrition deficits and gastrointestinal issues.
Inborn errors of immunity(IEI)disorders,formerly primary immune deficiency diseases,are a heterogeneous group of disorders with variable hereditary transitions,clinical manifestations,complications and varying disease severity.Many of the clinical symptoms,signs and complications in IEI patients can be attributed to inflammatory and immune dysregulatory processes due to loss of microbial diversity(dysbiosis).For example,in common variable immunodeficiency patients,the diversity of bacteria,but not fungi,in the gut microbiota has been found to be reduced and significantly altered.Again,this was associated with a more severe disease phenotype.Compromise of the STAT3/Th17 pathway in hyper-IgE syndrome may lead to dysbiosis of the oral microbiota in these patients,causing Candida albicans to switch from commensal to pathogenic.Modification of the microbiota can be used as a therapeutic approach in patients with IEI.Prebiotics,probiotics,postbiotics and fecal microbiota transplantation can be used to restore the balance of the gut microbiota and reduce pathogenicity in IEI patients.Clinical trials are currently underway to understand the impact of this dysbiosis on the phenotype of IEI diseases and its role in their treatment.
Gut microbiota and circulating metabolite dysbiosis predate important pathological changes in glucose metabolic disorders;however,comprehensive studies on impaired glucose tolerance(IGT),a diabetes mellitus(DM)precursor,are lacking.Here,we perform metagenomic sequencing and metabolomics on 47 pairs of individuals with IGT and newly diagnosed DM and 46 controls with normal glucose tolerance(NGT);patients with IGT are followed up after 4 years for progression to DM.Analysis of baseline data reveals significant differences in gut microbiota and serum metabolites among the IGT,DM,and NGT groups.In addition,13 types of gut microbiota and 17 types of circulating metabolites showed significant differences at baseline before IGT progressed to DM,including higher levels of Eggerthella unclassified,Coprobacillus unclassified,Clostridium ramosum,L-valine,L-norleucine,and L-isoleucine,and lower levels of Eubacterium eligens,Bacteroides faecis,Lachnospiraceae bacterium 3_1_46FAA,Alistipes senegalensis,Megaspaera elsdenii,Clostridium perfringens,α-linolenic acid,10E,12Z-octadecadienoic acid,and dodecanoic acid.A random forest model based on differential intestinal microbiota and circulating metabolites can predict the progression from IGT to DM(AUC=0.87).These results suggest that microbiome and metabolome dysbiosis occur in individuals with IGT and have important predictive values and potential for intervention in preventing IGT from progressing to DM.
The dysfunction of innate immunity components is one of the major drivers for ulcerative colitis(UC),and increasing reports indicate that the gut microbiome serves as an intermediate between genetic mutations and UC development.Here,we find that the IL-17 receptor subunit,CMTM4,is reduced in UC patients and dextran sulfate sodium(DSS)-induced colitis.The deletion of CMTM4(Cmtm4^(-/-))in mice leads to a higher susceptibility to DSS-induced colitis than in wild-type,and the gut microbiome significantly changes in composition.The causal role of the gut microbiome is confirmed with a cohousing experiment.We further identify that S100a8/9 is significantly up-regulated in Cmtm4^(-/-)colitis,with the block of its receptor RAGE that reverses the phenotype associated with the CMTM4 deficiency.CMTM4 deficiency rather suppresses S100a8/9 expression in vitro via the IL17 pathway,further supporting that the elevation of S100a8/9 in vivo is most likely a result of microbial dysbiosis.Taken together,the results suggest that CMTM4 is involved in the maintenance of intestinal homeostasis,suppression of S100a8/9,and prevention of colitis development.Our study further shows CMTM4 as a crucial innate immunity component,confirming its important role in UC development and providing insights into potential targets for the development of future therapies.