A wheat germ-rich diet preserves bone homeostasis by regulating gut microbiota and plasma metabolites in aged rats

Bone loss caused by ageing has become one of the leading health risk factors worldwide.Wheat germ(WG)is consists of high amounts of bioactive peptides,polyunsaturated fatty acids,and dietary fibre.Currently,WG has been proven to possess strong antioxidant and anti-infl ammatory properties.We recently explored the beneficial effects and relevant mechanisms of a WG-rich diet(2.5%and 5%WG,m/m)on bone homeostasis in aged rats.Our results showed that 5%WG supplementation for 12 months effectively attenuated ageing-induced microstructural damage and differentiation activity changes in the femur.The 5%WG supplementation also signifi cantly increased the levels of total antioxidant capacity(T-AOC),glutathione peroxidase(GSH-Px)(P<0.01),and superoxide dismutase(SOD)(P<0.05),and decreased infl ammatory cytokine levels(tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6))(P<0.01).Furthermore,the WG-rich diet reshaped the composition of the gut microbiota,enhancing short-chain fatty acids(SCFAs)-producing microbes and reducing infl ammation-related microbes.In addition,metabolomics analysis showed that 5%WG supplementation improved plasma metabolites related to bone metabolism.Conclusively,our study purports long-term WG-rich diet may preserve bone homeostasis by regulating gut microbiota and plasma metabolites in aged rats.

Cyanidin-3-O-glucoside alleviates trimethyltin chloride-induced neurodegeneration by maintaining glutamate homeostasis through modulation of the gut microbiota

Trimethyltin chloride(TMT)is a potent neurotoxin to cause neurodegeneration,especially in hippocampus.This study aimed to identify dietary components that can effectively attenuate TMT-induced neurodegeneration in humans.The predominant anthocyanin in human diets,cyanidin-3-O-glucoside(C3G,5 or 50 mg/kg),was given to mice for 16 days,and TMT(2.7 mg/kg)was injected intraperitoneally once on the eighth day.C3G(50 mg/kg)significantly alleviated TMT-induced seizures and subsequent cognitive impairment by ameliorating hippocampal neurodegeneration and synaptic dysfunction.Furthermore,C3G treatment restored glutamate homeostasis in brain and reversed glutamine synthetase(GS)inhibition in reactive astrogliosis and neuroinflammation,which are critical for C3G's neuroprotective effects.Notably,C3G decreased the lipopolysaccharide,tumor necrosis factor-α,interleukin-6,and interleukin-1βlevels in the mice,which potentially by modulating the relative abundance of Atopobiaceae and Lachnospiraceae in the gut.C3G may be a promising and practical dietary component for reducing TMT-induced neurodegeneration.

Soy polysaccharide maintains colonic homeostasis to protect from dextran sulphate sodium-induced colitis by modulating gut microbiota and intestinal epithelial regeneration

Soy polysaccharide(SP)has been reported to possess the properties of modulating gut microbiome diversity.Here,we aimed to explore the protective effects of SP against dextran sulphate sodium(DSS)-induced colitis.Pre-treatment with SP at a dosage of 400 mg/kg·day alleviated colitis symptoms,preventing the weight loss and colon shorten.SP suppressed DSS-induced inflammatory response and enhanced M1 to M2 macrophage polarization.Further investigation showed that SP significantly promoted the regeneration of crypt and the expansion of goblet cell production.In addition,bacterial 16S rRNA sequencing analysis showed that SP modulated the composition of fecal microbiota,including selectively increasing Lactobacillus relative abundance.Notably,SP treatment enriched the production of Lactobacillus-derived lactic acid,which was sensed by its specific G-protein-coupled receptor 81(Gpr81)/Wnt3/β-catenin signaling,and promoted the regeneration of intestinal stem cells.Fecal microbiome transplantation demonstrated that intestinal flora partially contributed to the beneficial effects of SP on preventing against colitis.In conclusion,SP exhibited the protective effects against colitis,which could be partly associated with modulating the composition of gut microbiota and enrichment of lactic acid.This study suggests that SP has potential to be developed as nutritional intervention to prevent colitis.

Theasinensin A attenuated diabetic development by restoring glucose homeostasis, improving hepatic steatosis and modulating gut microbiota in high-fat-diet/streptozotocin-induced diabetic mice

Theasinensin A(TSA),a dimer of epigallocatechin gallate,has been preliminarily demonstrated to have hypoglycemia and anti-inflammatory effects.However,little information is available on its potential mechanisms of anti-diabetes.Therefore,the present study aimed to investigate the influence of TSA on glucose and lipid metabolism and gut microbiota in high-fat-diet/streptozotocin-induced diabetic mice.As result,TSA improved polydipsia,polyphagia and impaired glucose tolerance of diabetic mice,declined the fasting blood glucose and hepatic triglyceride level,and enhanced the expression at mRNA level of insulin receptor substrate,phosphoinositide 3-kinase,protein kinase B and glucagon-like peptide 1 receptor(GLP-1R)in the diabetic liver.Moreover,TSA could restore the disorder of gut microbiota of diabetic mice.High-dose(100 mg/kg)TSA showed better benefi cial effects from the blood biochemical parameters,hepatic function and gut microbiota.In general,high-dose TSA significantly modulated gut microbiota by increasing the relative abundance of Akkermansia and decreasing the relative abundances of Acetatifactor,Anaerotruncus,Pseudofl avonifactor,Oscillibacter and Clostridium clusters.The results indicated that TSA could exert an anti-diabetes effect in diabetic mice through restoring glucose homeostasis,declining hepatic steatosis,activating insulin and GLP-1 signaling pathways,and ameliorating gut microbiota dysbiosis.

Intestinal microbiota participates in nonalcoholic fatty liver disease progression by affecting intestinal homeostasis

Nonalcoholic fatty liver disease(NAFLD)is a chronic liver disease with a pathogenesis that has not been fully elucidated.With the development of the theory of the gut-liver axis and the deepening of related research,the role of the intestinal tract in the pathogenesis of NAFLD has been investigated more.Intestinal microbiota,intestinal metabolites,and intestinal epithelial and immunebased barriers constitute the intestinal environment,which uses crosstalk to maintain the homeostasis of the intestinal environment.This paper reviews the progress in the study of intestinal microbiota,intestinal environment,and NAFLD and suggests that repair of intestinal functional balance may be a new idea for early prevention and intervention of NAFLD.

Intestinal microbiota in health and disease: Role of bifidobacteria in gut homeostasis

The pool of microbes inhabiting our body is known as &#x0201c;microbiota&#x0201d; and their collective genomes as &#x0201c;microbiome&#x0201d;. The colon is the most densely populated organ in the human body, although other parts, such as the skin, vaginal mucosa, or respiratory tract, also harbour specific microbiota. This microbial community regulates some important metabolic and physiological functions of the host, and drives the maturation of the immune system in early life, contributing to its homeostasis during life. Alterations of the intestinal microbiota can occur by changes in composition (dysbiosis), function, or microbiota-host interactions and they can be directly correlated with several diseases. The only disease in which a clear causal role of a dysbiotic microbiota has been demonstrated is the case of Clostridium difficile infections. Nonetheless, alterations in composition and function of the microbiota have been associated with several gastrointestinal diseases (inflammatory bowel disease, colorectal cancer, or irritable bowel syndrome), as well as extra-intestinal pathologies, such as those affecting the liver, or the respiratory tract (e.g., allergy, bronchial asthma, and cystic fibrosis), among others. Species of Bifidobacterium genus are the normal inhabitants of a healthy human gut and alterations in number and composition of their populations is one of the most frequent features present in these diseases. The use of probiotics, including bifidobacteria strains, in preventive medicine to maintain a healthy intestinal function is well documented. Probiotics are also proposed as therapeutic agents for gastrointestinal disorders and other pathologies. The World Gastroenterology Organization recently published potential clinical applications for several probiotic formulations, in which species of lactobacilli are predominant. This review is focused on probiotic preparations containing Bifidobacterium strains, alone or in combination with other bacteria, which have been tested in human clinical studies. In spite of extensive literature on and research into this topic, the degree of scientific evidence of the effectiveness of probiotics is still insufficient in most cases. More effort need to be made to design and conduct accurate human studies demonstrating the efficacy of probiotics in the prevention, alleviation, or treatment of different pathologies.

Internal connections between dietary intake and gut microbiota homeostasis in disease progression of ulcerative colitis:a review

Ulcerative colitis(UC)is a chronic systematic inflammation disorder with increasing incidence,unknown pathogenesis,limited drug treatment,and abundant medical expenses.Dietary intake,as a daily indispensable environment factor,is closely related to UC pathogenesis and prevention.The underlying interactions between dietary intake and UC progression are implicated with the modulation of gut microbiome as well as microbial metabolites,suggesting the complex and systematic characteristics of UC.However,the triangular relationships with dietary intake,gut microbiota homeostasis,and UC have not been well summarized so far.Here we review the recent studies of dietary intake on the regulation of gut microbiome homeostasis as well as modulation of UC progression.These findings suggest that varieties in dietary patterns result in the production of diverse microbial fermentation metabolites,which contribute to gut microbiome homeostasis through multiple manipulations including immune modulation,inftammation restriction as well as epithelial barrier maintenance,thus finally determine the fate of UC progression and give implications for functional food development for prevention and treatment of UC patients.

An Evaluation Method of Human Gut Microbial Homeostasis by Testing Specific Fecal Microbiota

Research on microecology has been carried out with broad perspectives in recent decades,which has enabled a better understanding of the gut microbiota and its roles in human health and disease.It is of great significance to routinely acquire the status of the human gut microbiota;however,there is no method to evaluate the gut microbiome through small amounts of fecal microbes.In this study,we found ten predominant groups of gut bacteria that characterized the whole microbiome in the human gut from a large-sample Chinese cohort,constructed a real-time quantitative polymerase chain reaction(qPCR)method and developed a set of analytical approaches to detect these ten groups of predominant gut bacterial species with great maneuverability,efficiency,and quantitative features.Reference ranges for the ten predominant gut bacterial groups were established,and we found that the concentration and pairwise ratios of the ten predominant gut bacterial groups varied with age,indicating gut microbial dysbiosis.By comparing the detection results of liver cirrhosis(LC)patients with those of healthy control subjects,differences were then analyzed,and a classification model for the two groups was built by machine learning.Among the six established classification models,the model established by using the random forest algorithm achieved the highest area under the curve(AUC)value and sensitivity for predicting LC.This research enables easy,rapid,stable,and reliable testing and evaluation of the balance of the gut microbiota in the human body,which may contribute to clinical work.

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.

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.

Copper homeostasis and neurodegenerative diseases

Copper,one of the most prolific transition metals in the body,is required for normal brain physiological activity and allows various functions to work normally through its range of concentrations.Copper homeostasis is meticulously maintained through a complex network of copper-dependent proteins,including copper transporters(CTR1 and CTR2),the two copper ion transporters the Cu-transporting ATPase 1(ATP7A)and Cu-transporting beta(ATP7B),and the three copper chaperones ATOX1,CCS,and COX17.Disruptions in copper homeostasis can lead to either the deficiency or accumulation of copper in brain tissue.Emerging evidence suggests that abnormal copper metabolism or copper binding to various proteins,including ceruloplasmin and metallothionein,is involved in the pathogenesis of neurodegenerative disorders.However,the exact mechanisms underlying these processes are not known.Copper is a potent oxidant that increases reactive oxygen species production and promotes oxidative stress.Elevated reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial dysfunction.Reactive oxygen species serve as key signaling molecules in copper-induced neuroinflammation,with elevated levels activating several critical inflammatory pathways.Additionally,copper can bind aberrantly to several neuronal proteins,including alphasynuclein,tau,superoxide dismutase 1,and huntingtin,thereby inducing neurotoxicity and ultimately cell death.This study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases,with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease pathogenesis.By synthesizing the current findings on the functions of copper in oxidative stress,neuroinflammation,mitochondrial dysfunction,and protein misfolding,we aim to elucidate the mechanisms by which copper contributes to a wide range of hereditary and neuronal disorders,such as Wilson's disease,Menkes'disease,Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,Huntington's disease,and multiple sclerosis.Potential clinically significant therapeutic targets,including superoxide dismutase 1,D-penicillamine,and 5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline,along with their associated therapeutic agents,are further discussed.Ultimately,we collate evidence that copper homeostasis may function in the underlying etiology of several neurodegenerative diseases and offer novel insights into the potential prevention and treatment of these diseases based on copper homeostasis.

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.

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.”

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.

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.

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.

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.

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.

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.