Interplay between creeping fat and gut microbiota: A brand-new perspective on fecal microbiota transplantation in Crohn's disease

Inflammatory bowel disease,particularly Crohn's disease(CD),has been linked to modifications in mesenteric adipose tissue(MAT)and the phenomenon known as"creeping fat"(CrF).The presence of CrF is believed to serve as a predictor for early clinical recurrence following surgical intervention in patients with CD.Notably,the incorporation of the mesentery during ileocolic resection for CD has been correlated with a decrease in surgical recurrence,indicating the significant role of MAT in the pathogenesis of CD.While numerous studies have indicated that dysbiosis of the gut microbiota is a critical factor in the development of CD,the functional implications of translocated microbiota within the MAT of CD patients remain ambiguous.This manuscript commentary discusses a recent basic research conducted by Wu et al.In their study,intestinal bacteria from individuals were transplanted into CD model mice,revealing that fecal microbiota trans-plantation(FMT)from healthy donors alleviated CD symptoms,whereas FMT from CD patients exacerbated these symptoms.Importantly,FMT was found to affect intestinal permeability,barrier function,and the levels of proinflammatory factors and adipokines.Collectively,these findings suggest that targeting MAT and CrF may hold therapeutic potential for patients with CD.However,the study did not evaluate the composition of the intestinal microbiota of the donors or the subsequent alterations in the gut microbiota.Overall,the gut microbiota plays a crucial role in the histopathology of CD,and thus,targeting MAT and CrF may represent a promising avenue for treatment in this patient population.

Longitudinal assessment of peripheral organ metabolism and the gut microbiota in an APP/PS1 transgenic mouse model of Alzheimer’s disease

Alzheimer’s disease not only affects the brain,but also induces metabolic dysfunction in peripheral organs and alters the gut microbiota.The aim of this study was to investigate systemic changes that occur in Alzheimer’s disease,in particular the association between changes in peripheral organ metabolism,changes in gut microbial composition,and Alzheimer’s disease development.To do this,we analyzed peripheral organ metabolism and the gut microbiota in amyloid precursor protein-presenilin 1(APP/PS1)transgenic and control mice at 3,6,9,and 12 months of age.Twelve-month-old APP/PS1 mice exhibited cognitive impairment,Alzheimer’s disease-related brain changes,distinctive metabolic disturbances in peripheral organs and fecal samples(as detected by untargeted metabolomics sequencing),and substantial changes in gut microbial composition compared with younger APP/PS1 mice.Notably,a strong correlation emerged between the gut microbiota and kidney metabolism in APP/PS1 mice.These findings suggest that alterations in peripheral organ metabolism and the gut microbiota are closely related to Alzheimer’s disease development,indicating potential new directions for therapeutic strategies.

Fecal microbiota transplantation in allergic diseases

Microorganisms such as bacteria,fungi,viruses,parasites living in the human intestine constitute the human intestinal microbiota.Dysbiosis refers to composi-tional and quantitative changes that negatively affect healthy gut microbiota.In recent years,with the demonstration that many diseases are associated with dysbiosis,treatment strategies targeting the correction of dysbiosis in the treat-ment of these diseases have begun to be investigated.Faecal microbiota trans-plantation(FMT)is the process of transferring faeces from a healthy donor to another recipient in order to restore the gut microbiota and provide a therapeutic benefit.FMT studies have gained popularity after probiotic,prebiotic,symbiotic studies in the treatment of dysbiosis and related diseases.FMT has emerged as a potential new therapy in the treatment of allergic diseases as it is associated with the maintenance of intestinal microbiota and immunological balance(T helper 1/T helper 2 cells)and thus suppression of allergic responses.In this article,the definition,application,safety and use of FMT in allergic diseases will be discussed with current data.

Unraveling brain aging through the lens of oral microbiota

The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative diseases.Recent studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention strategies.In this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and neurodegeneration.We also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.

Exploring the interaction between the gut microbiota and cyclic adenosine monophosphate-protein kinase A signaling pathway:a potential therapeutic approach for neurodegenerative diseases

The interaction between the gut microbiota and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enhances communication along the gut–brain axis.The gut microbiota influences the cAMP-PKA signaling pathway through its metabolites,which activates the vagus nerve and modulates the immune and neuroendocrine systems.Conversely,alterations in the cAMP-PKA signaling pathway can affect the composition of the gut microbiota,creating a dynamic network of microbial-host interactions.This reciprocal regulation affects neurodevelopment,neurotransmitter control,and behavioral traits,thus playing a role in the modulation of neurological diseases.The coordinated activity of the gut microbiota and the cAMP-PKA signaling pathway regulates processes such as amyloid-β protein aggregation,mitochondrial dysfunction,abnormal energy metabolism,microglial activation,oxidative stress,and neurotransmitter release,which collectively influence the onset and progression of neurological diseases.This study explores the complex interplay between the gut microbiota and cAMP-PKA signaling pathway,along with its implications for potential therapeutic interventions in neurological diseases.Recent pharmacological research has shown that restoring the balance between gut flora and cAMP-PKA signaling pathway may improve outcomes in neurodegenerative diseases and emotional disorders.This can be achieved through various methods such as dietary modifications,probiotic supplements,Chinese herbal extracts,combinations of Chinese herbs,and innovative dosage forms.These findings suggest that regulating the gut microbiota and cAMP-PKA signaling pathway may provide valuable evidence for developing novel therapeutic approaches for neurodegenerative diseases.

Exploring gut microbiota as a novel therapeutic target in Crohn’s disease: Insights and emerging strategies

Extensive research has investigated the etiology of Crohn’s disease(CD),encompassing genetic predisposition,lifestyle factors,and environmental triggers.Recently,the gut microbiome,recognized as the human body’s second-largest gene pool,has garnered significant attention for its crucial role in the patho-genesis of CD.This paper investigates the mechanisms underlying CD,focusing on the role of‘creeping fat’in disease progression and exploring emerging therapeutic strategies,including fecal microbiota transplantation,enteral nutri-tion,and therapeutic diets.Creeping fat has been identified as a unique patho-logical feature of CD and has recently been found to be associated with dysbiosis of the gut microbiome.We characterize this dysbiotic state by identi-fying key microbiome-bacteria,fungi,viruses,and archaea,and their contributions to CD pathogenesis.Additionally,this paper reviews contemporary therapies,empha-sizing the potential of biological therapies like fecal microbiota transplantation and dietary interventions.By elucidating the complex interactions between host-microbiome dynamics and CD pathology,this article aims to advance our under-standing of the disease and guide the development of more effective therapeutic strategies for managing CD.

Gut microbiota shifts in hepatitis B-related portal hypertension after transjugular intrahepatic portosystemic shunt:Mechanistic and clinical implications

In this article,we provide commentary on the recent article by Zhao et al.We focus on the shifts in the gut microbiota of patients with hepatitis B virus(HBV)-associated cirrhosis/portal hypertension(PH)following transjugular intrahepatic portosystemic shunt(TIPS)and the implications for understanding the mechanisms,diagnosis,and treatment.By comparing the gut microbiota composition and dynamic changes before and after TIPS in patients with and without hepatic encephalopathy,the authors found an increase in non-probiotic bacteria in those who developed hepatic encephalopathy post-TIPS,with Morganella species present only in the hepatic encephalopathy group.The gut microbiota changes post-TIPS among patients without the occurrence of hepatic encephalopathy suggest potential therapeutic benefits through prophylactic microbiome therapies.Furthermore,the specific gut microbiota alterations may hold promise to predict the risk of hepatic encephalopathy in individuals undergoing TIPS for HBVrelated PH.Despite these promising findings,future studies are needed to address limitations,including a small sample size,a relatively short evaluation period for gut microbiota alterations,the absence of data on dynamic alterations in gut microbiota post-TIPS and their correlation with blood ammonia levels,and the lack of validation in animal models.In conclusion,Zhao et al's study has shed new light on the link of gut microbiota with post-TIPS hepatic encephalopathy,potentially through the intricate gut-liver axis,and has important clinical implications for improving the management of patients with HBV-related PH.

Bidirectional regulation of the brain-gut-microbiota axis following traumatic brain injury

Traumatic brain injury is a prevalent disorder of the central nervous system.In addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury;however,the underlying pathogenesis remains unclear,and effective intervention methods are lacking.Intestinal dysfunction is a significant consequence of traumatic brain injury.Being the most densely innervated peripheral tissue in the body,the gut possesses multiple pathways for the establishment of a bidirectional“brain-gut axis”with the central nervous system.The gut harbors a vast microbial community,and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal,hormonal,and immune pathways.A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated complications.We comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury,with a specific focus on the complex biological processes of peripheral nerves,immunity,and microbes triggered by traumatic brain injury,encompassing autonomic dysfunction,neuroendocrine disturbances,peripheral immunosuppression,increased intestinal barrier permeability,compromised responses of sensory nerves to microorganisms,and potential effector nuclei in the central nervous system influenced by gut microbiota.Additionally,we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain injury.This review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effects of the“brain-gut-microbiota axis.”

Creeping fat and gut microbiota in Crohn’s disease

In this article,we explored the role of adipose tissue,especially mesenteric adipose tissue and creeping fat,and its association with the gut microbiota in the pathophysiology and progression of Crohn’s disease(CD).CD is a form of inflammatory bowel disease characterized by chronic inflammation of the gastrointestinal tract,influenced by genetic predisposition,gut microbiota dysbiosis,and environmental factors.Gut microbiota plays a crucial role in modulating immune response and intestinal inflammation and is associated with the onset and progression of CD.Further,visceral adipose tissue,particularly creeping fat,a mesenteric adipose tissue characterized by hypertrophy and fibrosis,has been implicated in CD pathogenesis,inflammation,and fibrosis.The bacteria from the gut microbiota may translocate into mesenteric adipose tissue,contributing to the formation of creeping fat and influencing CD progression.Although creeping fat may be a protective barrier against bacterial invasion,its expansion can damage adjacent tissues,leading to complications.Modulating gut microbiota through interventions such as fecal microbiota transplantation,probiotics,and prebiotics has shown potential in managing CD.However,more research is needed to clarify the mechanisms linking gut dysbiosis,creeping fat,and CD progression and develop targeted therapies for microbiota modulation and fat-related complications in patients with CD.

Gut microbiota-astrocyte axis: new insights into age-related cognitive decline

With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of astrocytes.The microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive function.This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases.This article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial metabolites.Finally,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s diseases.Our findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.

Characteristics of gut microbiota dysbiosis in patients with colorectal polyps

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.

Correlation between gut microbiota and tumor immune microenvironment:A bibliometric and visualized study

BACKGROUND In recent years,numerous reports have been published regarding the relationship between the gut microbiota and the tumor immune microenvironment(TIME).However,to date,no systematic study has been conducted on the relationship between gut microbiota and the TIME using bibliometric methods.AIM To describe the current global research status on the correlation between gut microbiota and the TIME,and to identify the most influential countries,research institutions,researchers,and research hotspots related to this topic.METHODS We searched for all literature related to gut microbiota and TIME published from January 1,2014,to May 28,2024,in the Web of Science Core Collection database.We then conducted a bibliometric analysis and created visual maps of the published literature on countries,institutions,authors,keywords,references,etc.,using CiteSpace(6.2R6),VOSviewer(1.6.20),and bibliometrics(based on R 4.3.2).RESULTS In total,491 documents were included,with a rapid increase in the number of publications starting in 2019.The country with the highest number of publications was China,followed by the United States.Germany has the highest number of citations in literature.From a centrality perspective,the United States has the highest influence in this field.The institutions with the highest number of publications were Shanghai Jiao Tong University and Zhejiang University.However,the institution with the most citations was the United States National Cancer Institute.Among authors,Professor Giorgio Trinchieri from the National Institutes of Health has the most local impact in this field.The most cited author was Fan XZ.The results of journal publications showed that the top three journals with the highest number of published papers were Frontiers in Immunology,Cancers,and Frontiers in Oncology.The three most frequently used keywords were gut microbiota,tumor microenvironment,and immunotherapy.CONCLUSION This study systematically elaborates on the research progress related to gut microbiota and TIME over the past decade.Research results indicate that the number of publications has rapidly increased since 2019,with research hotspots including“gut microbiota”,“tumor microenvironment”and“immunotherapy”.Exploring the effects of specific gut microbiota or derived metabolites on the behavior of immune cells in the TIME,regulating the secretion of immune molecules,and influencing immunotherapy are research hotspots and future research directions.

Effect of dietary fibre on the gastrointestinal microbiota during critical illness:A scoping review

The systemic effects of gastrointestinal(GI)microbiota in health and during chronic diseases is increasingly recognised.Dietary strategies to modulate the GI microbiota during chronic diseases have demonstrated promise.While changes in dietary intake can rapidly change the GI microbiota,the impact of dietary changes during acute critical illness on the microbiota remain uncertain.Dietary fibre is metabolised by carbohydrate-active enzymes and,in health,can alter GI microbiota.The aim of this scoping review was to describe the effects of dietary fibre supplementation in health and disease states,specifically during critical illness.Randomised controlled trials and prospective cohort studies that include adults(>18 years age)and reported changes to GI microbiota as one of the study outcomes using non-culture methods,were identified.Studies show dietary fibres have an impact on faecal microbiota in health and disease.The fibre,inulin,has a marked and specific effect on increasing the abundance of faecal Bifidobacteria.Short chain fatty acids produced by Bifidobacteria have been shown to be beneficial in other patient populations.Very few trials have evaluated the effect of dietary fibre on the GI microbiota during critical illness.More research is necessary to establish optimal fibre type,doses,duration of intervention in critical illness.

Effects of early postnatal gastric and colonic microbiota transplantation on piglet gut health

Background Diarrhea is a major cause of reduced growth and mortality in piglets during the suckling and weaning periods and poses a major threat to the global pig industry.Diarrhea and gut dysbiosis may in part be prevented via improved early postnatal microbial colonization of the gut.To secure better postnatal gut colonization,we hypothesized that transplantation of colonic or gastric content from healthy donors to newborn recipients would prevent diarrhea in the recipients in the post-weaning period.Our objective was to examine the impact of transplanting colonic or gastric content on health and growth parameters and paraclinical parameters in recipient single-housed piglets exposed to a weaning transition and challenged with enterotoxigenic Escherichia coli(ETEC).Methods Seventy-two 1-day-old piglets were randomized to four groups:colonic microbiota transplantation(CMT,n=18),colonic content filtrate transplantation(CcFT,n=18),gastric microbiota transplantation(GMT,n=18),or saline(CON,n=18).Inoculations were given on d 2 and 3 of life,and all piglets were milk-fed until weaning(d 20)and shortly after challenged with ETEC(d 24).We assessed growth,diarrhea prevalence,ETEC concentration,organ weight,blood parameters,small intestinal morphology and histology,gut mucosal function,and microbiota composition and diversity.Results Episodes of diarrhea were seen in all groups during both the milk-and the solid-feeding phase,possibly due to stress associated with single housing.However,CcFT showed lower diarrhea prevalence on d 27,28,and 29 compared to CON(all P<0.05).CcFT also showed a lower ETEC prevalence on d 27(P<0.05).CMT showed a higher alpha diversity and a difference in beta diversity compared to CON(P<0.05).Growth and other paraclinical endpoints were similar across groups.Conclusion In conclusion,only CcFT reduced ETEC-related post-weaning diarrhea.However,the protective effect was marginal,suggesting that higher doses,more effective modalities of administration,longer treatment periods,and better donor quality should be explored by future research to optimize the protective effects of transplantation.

Microbiota treatment of functional constipation:Current status and future prospects

Functional constipation(FC)is a common disorder that is characterized by diffi-cult stool passage,infrequent bowel movement,or both.FC is highly prevalent,recurs often,accompanies severe diseases,and affects quality of life;therefore,safe and effective therapy with long-term benefits is urgently needed.Microbiota treatment has potential value for FC treatment.Microbiota treatments include modulators such as probiotics,prebiotics,synbiotics,postbiotics,and fecal micro-biota transplantation(FMT).Some probiotics and prebiotics have been adopted,and the efficacy of other microbiota modulators is being explored.FMT is con-sidered an emerging field because of its curative effects;nevertheless,substantial work must be performed before clinical implementation.

Gut microbiota dysbiosis contributes toα-synuclein-related pathology associated with C/EBPβ/AEP signaling activation in a mouse model of Parkinson’s disease

Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosis is involved in the pathogenesis of Parkinson’s disease,whether it plays a causal role in motor dysfunction,and the mechanism underlying this potential effect,remain unknown.CCAAT/enhancer binding proteinβ/asparagine endopeptidase(C/EBPβ/AEP)signaling,activated by bacterial endotoxin,can promoteα-synuclein transcription,thereby contributing to Parkinson’s disease pathology.In this study,we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling,α-synuclein-related pathology,and motor symptoms using a rotenone-induced mouse model of Parkinson’s disease combined with antibiotic-induced microbiome depletion and fecal microbiota transplantation.We found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier,as well as activation of the C/EBP/AEP pathway,α-synuclein aggregation,and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor deficits.However,treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with antibiotics.Importantly,we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits,intestinal inflammation,and endotoxemia.Transplantation of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits,intestinal inflammation,endotoxemia,and intestinal barrier impairment.These results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits,C/EBPβ/AEP signaling activation,andα-synuclein-related pathology in a rotenone-induced mouse model of Parkinson’s disease.Additionally,our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that could help ameliorate the progression of motor deficits in patients with Parkinson’s disease.

Bile acids,gut microbiota,and therapeutic insights in hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver malignancy.The interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and progression.Under normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and BAs.The gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal homeostasis.Of note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC development.Therefore,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying hepatocarcinogenesis.In this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in HCC.Additionally,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered bacteria.In summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.

Elucidating the role of gut microbiota dysbiosis in hyperuricemia and gout:Insights and therapeutic strategies

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.

Bringing gut microbiota into the spotlight of clinical research and medical practice

Despite the increasing scientific interest and expanding role of gut microbiota(GM)in human health,it is rarely reported in case reports and deployed in cli-nical practice.Proteins and metabolites produced by microbiota contribute to im-mune system development,energy homeostasis and digestion.Exo-and endoge-nous factors can alter its composition.Disturbance of microbiota,also known as dysbiosis,is associated with various pathological conditions.Specific bacterial taxa and related metabolites are involved in disease pathogenesis and therefore can serve as a diagnostic tool.GM could also be a useful prognostic factor by predicting future disease onset and preventing hospital-associated infections.Ad-ditionally,it can influence response to treatments,including those for cancers,by altering drug bioavailability.A thorough understanding of its function has per-mitted significant development in therapeutics,such as probiotics and fecal trans-plantation.Hence,GM should be considered as a ground-breaking biological parameter,and it is advisable to be investigated and reported in literature in a more consistent and systematic way.

Layer chicken microbiota:a comprehensive analysis of spatial and temporal dynamics across all major gut sections

Background The gut microbiota influences chicken health,welfare,and productivity.A diverse and balanced microbiota has been associated with improved growth,efficient feed utilisation,a well-developed immune system,disease resistance,and stress tolerance in chickens.Previous studies on chicken gut microbiota have predominantly focused on broiler chickens and have usually been limited to one or two sections of the digestive system,under con-trolled research environments,and often sampled at a single time point.To extend these studies,this investigation examined the microbiota of commercially raised layer chickens across all major gut sections of the digestive system and with regular sampling from rearing to the end of production at 80 weeks.The aim was to build a detailed picture of microbiota development across the entire digestive system of layer chickens and study spatial and temporal dynamics.Results The taxonomic composition of gut microbiota differed significantly between birds in the rearing and pro-duction stages,indicating a shift after laying onset.Similar microbiota compositions were observed between proven-triculus and gizzard,as well as between jejunum and ileum,likely due to their anatomical proximity.Lactobacil-lus dominated the upper gut in pullets and the lower gut in older birds.The oesophagus had a high proportion of Proteobacteria,including opportunistic pathogens such as Gallibacterium.Relative abundance of Gallibacterium increased after peak production in multiple gut sections.Aeriscardovia was enriched in the late-lay phase compared to younger birds in multiple gut sections.Age influenced microbial richness and diversity in different organs.The upper gut showed decreased diversity over time,possibly influenced by dietary changes,while the lower gut,specifi-cally cecum and colon,displayed increased richness as birds matured.However,age-related changes were inconsist-ent across all organs,suggesting the influence of organ-specific factors in microbiota maturation.Conclusion Addressing a gap in previous research,this study explored the microbiota across all major gut sections and tracked their dynamics from rearing to the end of the production cycle in commercially raised layer chickens.This study provides a comprehensive understanding of microbiota structure and development which help to develop targeted strategies to optimise gut health and overall productivity in poultry production.