More on the interplay between gut microbiota,autophagy,and inflammatory bowel disease is needed

The concept of inflammatory bowel disease(IBD),which encompasses Crohn’s disease and ulcerative colitis,represents a complex and growing global health concern resulting from a multifactorial etiology.Both dysfunctional autophagy and dysbiosis contribute to IBD,with their combined effects exacerbating the related inflammatory condition.As a result,the existing interconnection between gut microbiota,autophagy,and the host’s immune system is a decisive factor in the occurrence of IBD.The factors that influence the gut microbiota and their impact are another important point in this regard.Based on this initial perspective,this manuscript briefly highlighted the intricate interplay between the gut microbiota,autophagy,and IBD pathogenesis.In addition,it also addressed the potential targeting of the microbiota and modulating autophagic pathways for IBD therapy and proposed suggestions for future research within a more specific and expanded context.Further studies are warranted to explore restoring microbial balance and regulating autophagy mechanisms,which may offer new therapeutic avenues for IBD management and to delve into personalized treatment to alleviate the related burden.

Beyond bacteria:Role of non-bacterial gut microbiota species in inflammatory bowel disease and colorectal cancer progression

This letter emphasizes the need to expand discussions on gut microbiome’s role in inflammatory bowel disease(IBD)and colorectal cancer(CRC)by including the often-overlooked non-bacterial components of the human gut flora.It highlights how viral,fungal and archaeal inhabitants of the gut respond towards gut dysbiosis and contribute to disease progression.Viruses such as bacteriophages target certain bacterial species and modulate the immune system.Other viruses found associated include Epstein-Barr virus,human papillomavirus,John Cunningham virus,cytomegalovirus,and human herpes simplex virus type 6.Fungi such as Candida albicans and Malassezia contribute by forming tissue-invasive filaments and producing inflammatory cytokines,respectively.Archaea,mainly methanogens are also found altering the microbial fermentation pathways.This correspondence,thus underscores the significance of considering the pathological and physiological mechanisms of the entire spectrum of the gut microbiota to develop effective therapeutic interventions for both IBD and CRC.

Gut Microbiota: Physiology and Relationship with Inflammatory Bowel Disease

The intestinal microbiota, which evolved over tens of thousands of years along with their human hosts, constitutes a complex and diverse ecosystem whose composition differs from person to person. Accumulating evidence indicates that commensal bacteria exert numerous beneficial physiological effects for humans, including nutrition, protection, metabolism, organ development and immunomodulation. However, mucosal immune responses to intestinal microflora require precise control to allow appropriate defense against potential pathogens but restrict the immune response to beneficial resident bacteria. The task of intestinal homeostasis is accomplished by epithelium and specialized immune system in the gastrointestinal tract. Alternation in the composition of the bacterial community, consisting of increased representation of harmful species or under presence of protective species, or dysbiosis has been linked to various chronic and inflammatory disorders, such as inflammatory bowel disease. An improved understanding of the underlying molecular mechanisms of host-microorganism interactions could bring new insights into onset and pathogenesis of several autoimmune diseases. This review will discuss physiologic properties of commensal microbiota and how dysregulated immune responses to them contribute to chronic mucosal inflammation.

Gut microbiome-based thiamine metabolism contributes to the protective effect of one acidic polysaccharide from Selaginella uncinata(Desv.)Spring against inflammatory bowel disease

Inflammatory bowel disease(IBD)is a serious disorder,and exploration of active compounds to treat it is necessary.An acidic polysaccharide named SUSP-4 was purified from Selaginella uncinata(Desv.)Spring,which contained galacturonic acid,galactose,xylose,arabinose,and rhamnose with the main chain structure of→4)-α-d-GalAp-(1→and→6)-β-d-Galp-(1→and the branched structure of→5)-α-l-Araf-(1→.Animal experiments showed that compared with Model group,SUSP-4 significantly improved body weight status,disease activity index(DAI),colonic shortening,and histopathological damage,and elevated occludin and zonula occludens protein 1(ZO-1)expression in mice induced by dextran sulfate sodium salt(DSS).16S ribosomal RNA(rRNA)sequencing indicated that SUSP-4 markedly downregulated the level of Akkermansia and Alistipes.Metabolomics results confirmed that SUSP-4 obviously elevated thiamine levels compared with Model mice by adjusting thiamine metabolism,which was further confirmed by a targeted metabolism study.Fecal transplantation experiments showed that SUSP-4 exerted an anti-IBD effect by altering the intestinal flora in mice.A mechanistic study showed that SUSP-4 markedly inhibited macrophage activation by decreasing the levels of phospho-nuclear factor kappa-B(p-NF-κB)and cyclooxygenase-2(COX-2)and elevating NF-E2-related factor 2(Nrf2)levels compared with Model group.In conclusion,SUSP-4 affected thiamine metabolism by regulating Akkermania and inhibited macrophage activation to adjust NF-κB/Nrf2/COX-2-mediated inflammation and oxidative stress against IBD.This is the first time that plant polysaccharides have been shown to affect thiamine metabolism against IBD,showing great potential for in-depth research and development applications.

Dual-targeted treatment for inflammatory bowel disease:Whether fecal microbiota transplantation can be an important part of it

Inflammatory bowel disease(IBD)is a chronic gastrointestinal inflammatory disease.With the emergence of biologics and other therapeutic methods,two biologics or one biologic combined with a novel small-molecule drug has been proposed in recent years to treat IBD.Although treatment strategies for IBD are being optimized,their efficacy and risks still warrant further consideration.This editorial explores the current risks associated with dual-targeted treatment for IBD and the great potential that fecal microbiota transplantation(FMT)may have for use in combination therapy for IBD.We are focused on addressing refractory IBD or biologically resistant IBD based on currently available dual-targeted treatment by incorporating FMT as part of this dual-targeted treatment.In this new therapy regimen,FMT represents a promising combination therapy.

Gut microbiota in gastrointestinal diseases:Insights and therapeutic strategies

Considering the bidirectional crosstalk along the gut-liver axis,gut-derived microorganisms and metabolites can be released into the liver,potentially leading to liver injury.In this editorial,we comment on several studies published in the recent issue of the World Journal of Gastroenterology.We focus specifically on the roles of gut microbiota in selected gastrointestinal(GI)diseases that are prevalent,such as inflammatory bowel disease,metabolic dysfunction-associated steatotic liver disease,and hepatitis B virus-related portal hypertension.Over the past few decades,findings from both preclinical and clinical studies have indicated an association between compositional and metabolic changes in the gut microbiota and the pathogenesis of the aforementioned GI disorders.However,studies elucidating the mechanisms underlying the host-microbiota interactions remain limited.The purpose of this editorial is to summarize current findings and provide insights regarding the context-specific roles of gut microbiota.Ultimately,the discovery of microbiome-based biomarkers may facilitate disease diagnosis and the development of personalized medicine.

Navigating new horizons in inflammatory bowel disease:Integrative approaches and innovations

This editorial offers an updated synthesis of the major advancements in the management and treatment of inflammatory bowel disease(IBD),as documented in the World Journal of Gastroenterology between 2023 and early 2024.This editorial explores substantial developments across key research areas,such as intestinal microecology,computational drug discovery,dual biologic therapy,telemedicine,and the integration of lifestyle changes into patient care.Furthermore,the discussion of emerging topics,including bowel preparation in colonoscopy,the impact of the coronavirus disease 2019 pandemic,and the intersection between IBD and mental health,reflects a shift toward a more holistic approach to IBD research.By integrating these diverse areas of research,this editorial seeks to promote a holistic and multidisciplinary approach to IBD treatment,combining emerging technologies,personalized medicine,and conventional therapies to improve patient outcomes.

Critical analysis of the effects of proton pump inhibitors on inflammatory bowel disease:An updated review

This letter critically evaluates the effects of proton pump inhibitors(PPIs)on inflammatory bowel disease,particularly focusing on Crohn's disease(CD)and ulcerative colitis(UC),as discussed in Liang et al’s recent review.While the review provides significant insights,it relies heavily on cross-sectional and observational studies,which limits the ability to draw causal inferences.The heterogeneous study populations and inconsistent definitions of long-term PPI use further complicate the findings.This letter also highlights the need for rigorous control of confounding factors and considers the potential publication bias in the existing literature.The implications of these issues are discussed in the context of both CD and UC,and future research directions are proposed to address these shortcomings.

Gut microbiota,inflammatory bowel disease and colorectal cancer

The gut microbiota is a complex community of microorganisms that inhabit the digestive tracts of humans,living in symbiosis with the host.Dysbiosis,characterized by an imbalance between the beneficial and opportunistic gut microbiota,is associated with several gastrointestinal disorders,such as irritable bowel syndrome(IBS);inflammatory bowel disease(IBD),represented by ulcerative colitis and Crohn’s disease;and colorectal cancer(CRC).Dysbiosis can disrupt the mucosal barrier,resulting in perpetuation of inflammation and carcinogenesis.The increase in some specific groups of harmful bacteria,such as Escherichia coli(E.coli)and enterotoxigenic Bacteroides fragilis(ETBF),has been associated with chronic tissue inflammation and the release of pro-inflammatory and carcinogenic mediators,increasing the chance of developing CRC,following the inflammationdysplasia-cancer sequence in IBD patients.Therefore,the aim of the present review was to analyze the correlation between changes in the gut microbiota and the development and maintenance of IBD,CRC,and IBD-associated CRC.Patients with IBD and CRC have shown reduced bacterial diversity and abundance compared to healthy individuals,with enrichment of Firmicute sand Bacteroidetes.Specific bacteria are also associated with the onset and progression of CRC,such as Fusobacterium nucleatum,E.coli,Enterococcus faecalis,Streptococcus gallolyticus,and ETBF.Future research can evaluate the advantages of modulating the gut microbiota as preventive measures in CRC high-risk patients,directly affecting the prognosis of the disease and the quality of life of patients.

Resveratrol and its derivates improve inflammatory bowel disease by targeting gut microbiota and inflammatory signaling pathways

Inflammatory bowel disease(IBD)is a chronic inflammatory lesion of the intestine,mainly manifested by infiltration of intestinal inflammatory cells and imbalance of gut microbiota.Conventional treatments for IBD include antibiotics,immunosuppressive agents,5-aminosalicylic acid,steroids and surgery,which have high toxic side effects.Resveratrol is a natural polyphenol,and its various derivatives have anti-oxidation and anti-inflammatory properties.In this paper,we comprehensively review the mechanism of resveratrol and its derivates to alleviate IBD by improving intestinal barrier,regulating the unbalanced gut microbiota,and targeting various inflammatory signaling pathways.

Bile acids and their receptors: Potential therapeutic targets in inflammatory bowel disease

Chronic and recurrent inflammatory disorders of the gastrointestinal tract caused by a complex interplay between genetics and intestinal dysbiosis are called inflammatory bowel disease.As a result of the interaction between the liver and the gut microbiota,bile acids are an atypical class of steroids produced in mammals and traditionally known for their function in food absorption.With the development of genomics and metabolomics,more and more data suggest that the pathophysiological mechanisms of inflammatory bowel disease are regulated by bile acids and their receptors.Bile acids operate as signalling molecules by activating a variety of bile acid receptors that impact intestinal flora,epithelial barrier function,and intestinal immunology.Inflammatory bowel disease can be treated in new ways by using these potential molecules.This paper mainly discusses the increasing function of bile acids and their receptors in inflammatory bowel disease and their prospective therapeutic applications.In addition,we explore bile acid metabolism and the interaction of bile acids and the gut microbiota.

Role of the gut microbiota in inflammatory bowel disease pathogenesis: What have we learnt in the past 10 years?

Our understanding of the microbial involvement in inflammatory bowel disease (IBD) pathogenesis has increased exponentially over the past decade. The development of newer molecular tools for the global assessment of the gut microbiome and the identification of nucleotide-binding oligomerization domain-containing protein 2 in 2001 and other susceptibility genes for Crohn’s disease in particular has led to better understanding of the aetiopathogenesis of IBD. The microbial studies have elaborated the normal composition of the gut microbiome and its perturbations in the setting of IBD. This altered microbiome or “dysbiosis” is a key player in the protracted course of inflammation in IBD. Numerous genome-wide association studies have identified further genes involved in gastrointestinal innate immunity (including polymorphisms in genes involved in autophagy: ATG16L1 and IGRM), which have helped elucidate the relationship of the local innate immunity with the adjacent luminal bacteria. These developments have also spurred the search for specific pathogens which may have a role in the metamorphosis of the gut microbiome from a symbiotic entity to a putative pathogenic one. Here we review advances in our understanding of microbial involvement in IBD pathogenesis over the past 10 years and offer insight into how this will shape our therapeutic management of the disease in the coming years.

Gut-lung crosstalk in pulmonary involvement with inflammatory bowel diseases

Pulmonary abnormalities,dysfunction or hyper-reactivity occurs in association with inflammatory bowel disease(IBD) more frequently than previously recognized.Emerging evidence suggests that subtle inflammation exists in the airways among IBD patients even in the absence of any bronchopulmonary symptoms,and with normal pulmonary functions. The pulmonary impairment is more pronounced in IBD patients with active disease than in those in remission. A growing number of case reports show that the IBD patients develop rapidly progressive respiratory symptoms after colectomy,with failure to isolate bacterial pathogens on repeated sputum culture,and often request oral corticosteroid therapy. All the above evidence indicates that the inflammatory changes in both the intestine and lung during IBD. Clinical or subclinical pulmonary inflammation accompanies the main inflammation of the bowel.Although there are clinical and epidemiological reports of chronic inflammation of the pulmonary and intestinal mucosa in IBD,the detailed mechanisms of pulmonaryintestinal crosstalk remain unknown. The lung has no anatomical connection with the main inflammatory site of the bowel. Why does the inflammatory process shift from the gastrointestinal tract to the airways? The clinical and subclinical pulmonary abnormalities,dysfunction,or hyper-reactivity among IBD patients need further evaluation. Here,we give an overview of the concordance between chronic inflammatory reactions in the airways and the gastrointestinal tract. A better understanding of the possible mechanism of the crosstalk among the distant organs will be beneficial in identifying therapeutic strategies for mucosal inflammatory diseases such as IBD and allergy.

Enzyme-like biomimetic oral-agent enabling modulating gut microbiota and restoring redox homeostasis to treat inflammatory bowel disease

Reactive oxygen species(ROS),immune dysregulation-induced inflammatory outbreaks and microbial imbalance play critical roles in the development of inflammatory bowel disease(IBD).Herein,a novel enzyme-like biomimetic oral-agent ZnPBA@YCW has been developed,using yeast cell wall(YCW)as the outer shell and zinc-doped Prussian blue analogue(ZnPBA)nanozyme inside.When orally administered,the ZnPBA@YCW is able to adhere to Escherichia coli occupying the ecological niche in IBD and subsequently release the ZnPBA nanozyme for removal of E.coli,meanwhile exhibiting improved intestinal epithelial barrier repair.Moreover,it is found that the ZnPBA nanozyme exhibits remarkable capability in restoring redox homeostasis by scavenging ROS and inhibiting NF-κB signaling pathway.More importantly,the 16S ribosomal RNA gene sequencing results indicate that post-oral of ZnPBA@YCW can effectively regulate gut microbiota by enhancing the bacterial richness and diversity,significantly increasing the abundance of probiotics with anti-inflammatory phenotype while downgrading pathogenic E.coli to the same level as normal mice.Such a novel nanomedicine provides a new idea for efficient treating those ROS-mediated diseases accompanying with flora disorders.

Causality Between Gut Microbiota and Inflammatory Bowel Disease:A Bidirectional Mendelian Randomization Study

The exact relationship between inflammatory bowel disease(IBD)and gut microbiota(GM)is still unclear.This study aimed to explore the cause-and-effect relationship between IBD and GM by Mendelian randomization analysis.The IBD data used in this study were obtained from Genome-Wide Association Studies.The GM data were from the Dutch Microbiome Project and included 207 taxa and 205 microbiota-associated pathways.Multivariate Mendelian randomization analysis was performed to investigate the relationship between GM and IBD.The results demonstrated that susceptibility to developing IBD is negatively correlated with class Clostridia(OR=0.80,P=0.003),family Sutterellacea(OR=0.87,P=0.014),genus Coprobacter(OR=0.90,P=0.009),order Clostridiales(OR=0.80,P=0.003),phylum Firmicutes(OR=0.82,P=0.002)and Coprobacter fastidiosus(OR=0.90,P=0.009).Conversely,the risk of developing IBD was positively correlated with the phosphopantothenate biosynthesis I pathway(OR=1.17,P=0.006),Bacteroides caccae(OR=1.14,P=0.021)and Bacteroides uniformis(OR=1.26,P=0.003).Reverse causality was found between the phosphopantothenate biosynthesis I pathway and IBD(OR=1.03,P=0.04),but not for the remaining specific GM taxa.In conclusion,our study demonstrated a causal relationship between specific GM features and IBD.

The protective effect of carnosic acid on dextran sulfate sodium-induced colitis based on metabolomics and gut microbiota analysis

Accumulating evidence suggests that the gut microbiota plays an important role in the pathogenesis of inflammatory bowel disease(IBD).Carnosic acid(CA)is a major antioxidant component of rosemary and sage.Herein,we investigated the protective effects of dietary CA on dextran sodium sulfate(DSS)-induced colitis mouse model with an emphasis on its impact on the composition and metabolic function of gut microbiota.We found that CA effectively attenuated DSS-stimulated colitis in mice,as evidenced by reduced disease activity index(DAI),and systemic and colonic inflammation.Additionally,CA restored microbial diversity and improved the composition of gut microbiota in DSS-treated mice.Moreover,Spearman’s correlation coefficient showed a significant correlation between the fecal metabolites and the gut microbiota species.Changes in gut microbiota and the correlated metabolites might partially explain CA’s anti-inflammatory effects against colitis.Future clinical trials are needed to determine the therapeutic effects and mechanisms of CA on IBD in humans.

Immune response modulation in inflammatory bowel diseases by Helicobacter pylori infection

Many studies point to an association between Helicobacter pylori(H.pylori)infection and inflammatory bowel diseases(IBD).Although controversial,this association indicates that the presence of the bacterium somehow affects the course of IBD.It appears that H.pylori infection influences IBD through changes in the diversity of the gut microbiota,and hence in local chemical characteristics,and alteration in the pattern of gut immune response.The gut immune response appears to be modulated by H.pylori infection towards a less aggressive inflammatory response and the establishment of a targeted response to tissue repair.Therefore,a T helper 2(Th2)/macrophage M2 response is stimulated,while the Th1/macrophage M1 response is suppressed.The immunomodulation appears to be associated with intrinsic factors of the bacteria,such as virulence factors-such oncogenic protein cytotoxin-associated antigen A,proteins such H.pylori neutrophil-activating protein,but also with microenvironmental changes that favor permanence of H.pylori in the stomach.These changes include the increase of gastric mucosal pH by urease activity,and suppression of the stomach immune response promoted by evasion mechanisms of the bacterium.Furthermore,there is a causal relationship between H.pylori infection and components of the innate immunity such as the NLR family pyrin domain containing 3 inflammasome that directs IBD toward a better prognosis.

Distinct gut microbiota profiles in patients with primary sclerosing cholangitis and ulcerative colitis

To characterize the gut bacterial microbiota of patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC). METHODSStool samples were collected and relevant clinical data obtained from 106 study participants, 43 PSC patients with (n = 32) or without (n = 11) concomitant inflammatory bowel disease, 32 UC patients, and 31 healthy controls. The V3 and V4 regions of the 16S ribosomal RNA gene were sequenced on Illumina MiSeq platform to cover low taxonomic levels. Data were further processed in QIIME employing MaAsLin and LEfSe tools for analysis of the output data. RESULTSMicrobial profiles in both PSC and UC were characterized by low bacterial diversity and significant change in global microbial composition. Rothia, Enterococcus, Streptococcus, Veillonella, and three other genera were markedly overrepresented in PSC regardless of concomitant inflammatory bowel disease (IBD). Rothia, Veillonella and Streptococcus were tracked to the species level to identify Rothia mucilaginosa, Streptococcus infantus, S. alactolyticus, and S. equi along with Veillonella parvula and V. dispar. PSC was further characterized by decreased abundance of Adlercreutzia equolifaciens and Prevotella copri. Decrease in genus Phascolarctobacterium was linked to presence of colonic inflammation regardless of IBD phenotype. Akkermansia muciniphila, Butyricicoccus pullicaecorum and Clostridium colinum were decreased in UC along with genus Roseburia. Low levels of serum albumin were significantly correlated with enrichment of order Actinomycetales. CONCLUSIONPSC is associated with specific gut microbes independently of concomitant IBD and several bacterial taxa clearly distinguish IBD phenotypes (PSC-IBD and UC).

Pathological and therapeutic interactions between bacteriophages,microbes and the host in inflammatory bowel disease

The intestinal microbiome is a dynamic system of interactions between the host and its microbes. Under physiological conditions,a fine balance and mutually beneficial relationship is present. Disruption of this balance is a hallmark of inflammatory bowel disease(IBD). Whether an altered microbiome is the consequence or the cause of IBD is currently not fully understood. The pathogenesis of IBD is believed to be a complex interaction between genetic predisposition,the immune system and environmental factors. In the recent years,metagenomic studies of the human microbiome have provided useful data that are helping to assemble the IBD puzzle. In this review,we summarize and discuss current knowledge on the composition of the intestinal microbiota in IBD,hostmicrobe interactions and therapeutic possibilities using bacteria in IBD. Moreover,an outlook on the possible contribution of bacteriophages in the pathogenesis and therapy of IBD is provided.

Antioxidant and anti-inflammatory roles of tea polyphenols in inflammatory bowel diseases

Polyphenols,including phenolic acids,flavonoids,and procyanidins,are abundant in food and beverage derived from plants.Tea(Camellia sinensis)is particularly rich in polyphenols(e.g.,catechins,theaflavins,thearubigins,gallic acid,and flavonols),which are thought to contribute to the health benefits of tea.High intake of tea polyphenols has been described to prevent and/or attenuate a variety of chronic pathological conditions like cardiovascular diseases,neurodegenerative diseases,diabetes,and cancer.This review focuses on established antioxidant and anti-inflammatory properties of tea polyphenols and underlying mechanisms of their involvement in inflammatory bowel diseases(IBD).Tea polyphenols act as efficient antioxidants by inducing an endogenous antioxidant defense system and maintaining intracellular redox homeostasis.Tea polyphenols also regulate signaling pathways such as nuclear factor-κB,activator protein 1,signal transducer and activator of transcriptions,and nuclear factor E2-related factor 2,which are associated with IBD development.Accumulating pieces of evidence have indicated that tea polyphenols enhance epithelial barrier function and improve gut microbial dysbiosis,contributing to the management of inflammatory colitis.Therefore,this study suggests that supplementation of tea polyphenols could prevent inflammatory conditions and improve the outcome of patients with IBD.