AIM To investigate gut microbial diversity and the interventional effect of Xiaoyaosan(XYS) in a rat model of functional dyspepsia(FD) with liver depression-spleen deficiency syndrome. METHODS The FD with liver depres...AIM To investigate gut microbial diversity and the interventional effect of Xiaoyaosan(XYS) in a rat model of functional dyspepsia(FD) with liver depression-spleen deficiency syndrome. METHODS The FD with liver depression-spleen deficiency syndrome rat model was established through classic chronic mild unpredictable stimulation every day. XYS group rats received XYS 1 h before the stimulation. The models were assessed by parameters including state ofthe rat, weight, sucrose test result and open-field test result. After 3 wk, the stools of rats were collected and genomic DNA was extracted. PCR products of the V4 region of 16 S rD NA were sequenced using a barcoded Illumina paired-end sequencing technique. The primary composition of the microbiome in the stool samples was determined and analyzed by cluster analysis.RESULTS Rat models were successfully established, per data from rat state, weight and open-field test. The microbiomes contained 20 phyla from all samples. Firmicutes, Bacteroidetes, Proteobacteria, Cyanobacteria and Tenericutes were the most abundant taxonomic groups. The relative abundance of Firmicutes, Proteobacteria and Cyanobacteria in the model group was higher than that in the normal group. On the contrary, the relative abundance of Bacteroidetes in the model group was lower than that in the normal group. Upon XYS treatment, the relative abundance of all dysregulated phyla was restored to levels similar to those observed in the normal group. Abundance clustering heat map of phyla corroborated the taxonomic distribution. CONCLUSION The microbiome relative abundance of FD rats with liver depression-spleen deficiency syndrome was significantly different from the normal cohort. XYS intervention may effectively adjust the gut dysbacteriosis in FD.展开更多
The gut-liver axis denotes the intricate connection and interaction between gut microbiome and liver, in which compositional and functional shifts in gut microbiome affect host metabolism. Hepatic portal vein of the b...The gut-liver axis denotes the intricate connection and interaction between gut microbiome and liver, in which compositional and functional shifts in gut microbiome affect host metabolism. Hepatic portal vein of the blood circulation system has been thought to be the major route for metabolite transportation in the gut-liver axis, but the existence and importance of other routes remain elusive. Here, we perform metabolome comparison in blood circulation and mesenteric lymph systems and identify significantly shifted metabolites in serum and mesentery. Using cellular assays, we find that the majority of decreased metabolites in lymph system under high-fat diet are effective in alleviating metabolic disorders, indicating a high potential of lymph system in regulating liver metabolism. Among those, a representative metabolite, L-carnitine, reduces diet-induced obesity in mice. Metabolic tracing analysis identifies that L-carnitine is independently transported by the mesenteric lymph system, serving as an example that lymph circulation comprises a second route in the gut-liver axis to modulate liver metabolism. Our study provides new insights into metabolite transportation via mesenteric lymph system in the gut-liver axis, offers an extended scope for the investigations in host-gut microbiota metabolic interactions and potentially new targets in the treatment of metabolic disorders.展开更多
BACKGROUND In recent years,the incidence of type 2 diabetes(T2DM)has shown a rapid growth trend.Goto Kakizaki(GK)rats are a valuable model for the study of T2DM and share common glucose metabolism features with human ...BACKGROUND In recent years,the incidence of type 2 diabetes(T2DM)has shown a rapid growth trend.Goto Kakizaki(GK)rats are a valuable model for the study of T2DM and share common glucose metabolism features with human T2DM patients.A series of studies have indicated that T2DM is associated with the gut microbiota composition and gut metabolites.We aimed to systematically characterize the faecal gut microbes and metabolites of GK rats and analyse the relationship between glucose and insulin resistance.AIM To evaluate the gut microbial and metabolite alterations in GK rat faeces based on metagenomics and untargeted metabolomics.METHODS Ten GK rats(model group)and Wistar rats(control group)were observed for 10 wk,and various glucose-related indexes,mainly including weight,fasting blood glucose(FBG)and insulin levels,homeostasis model assessment of insulin resistance(HOMA-IR)and homeostasis model assessment ofβcell(HOMA-β)were assessed.The faecal gut microbiota was sequenced by metagenomics,and faecal metabolites were analysed by untargeted metabolomics.Multiple metabolic pathways were evaluated based on the differential metabolites identified,and the correlations between blood glucose and the gut microbiota and metabolites were analysed.RESULTS The model group displayed significant differences in weight,FBG and insulin levels,HOMA-IR and HOMA-βindexes(P<0.05,P<0.01)and a shift in the gut microbiota structure compared with the control group.The results demonstrated significantly decreased abundances of Prevotella sp.CAG:604 and Lactobacillus murinus(P<0.05)and a significantly increased abundance of Allobaculum stercoricanis(P<0.01)in the model group.A correlation analysis indicated that FBG and HOMA-IR were positively correlated with Allobaculum stercoricanis and negatively correlated with Lactobacillus murinus.An orthogonal partial least squares discriminant analysis suggested that the faecal metabolic profiles differed between the model and control groups.Fourteen potential metabolic biomarkers,including glycochenodeoxycholic acid,uric acid,13(S)-hydroxyoctadecadienoic acid(HODE),N-acetylaspartate,β-sitostenone,sphinganine,4-pyridoxic acid,and linoleic acid,were identified.Moreover,FBG and HOMA-IR were found to be positively correlated with glutathione,13(S)-HODE,uric acid,4-pyridoxic acid and allantoic acid and negatively correlated with 3-α,7-α,chenodeoxycholic acid glycine conjugate and 26-trihydroxy-5-β-cholestane(P<0.05,P<0.01).Allobaculum stercoricanis was positively correlated with linoleic acid and sphinganine(P<0.01),and 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate was negatively associated with Prevotella sp.CAG:604(P<0.01).The metabolic pathways showing the largest differences were arginine biosynthesis;primary bile acid biosynthesis;purine metabolism;linoleic acid metabolism;alanine,aspartate and glutamate metabolism;and nitrogen metabolism.CONCLUSION Metagenomics and untargeted metabolomics indicated that disordered compositions of gut microbes and metabolites may be common defects in GK rats.展开更多
OBJECTIVE: To investigate composition of gut microbial community in a rat model of functional dyspepsia(FD) and to explore the interventional effects of Simo Tang(四磨汤, SMT). METHODS: A rat model of FD was establish...OBJECTIVE: To investigate composition of gut microbial community in a rat model of functional dyspepsia(FD) and to explore the interventional effects of Simo Tang(四磨汤, SMT). METHODS: A rat model of FD was established through the tail-clamping stimulation method. The rat model of FD was assessed by the state of rats, their weight, sucrose preference rate, and intestinal propulsion rate. The DNA was extracted from stool samples after treatment with SMT. Amplified polymerase chain reaction(PCR) products of the 16S r DNA were sequenced using Novase Q6000 after construction of libraries. Composition of gut microbial community in the stool samples was determined and analyzed by cluster analysis, bioinformatic analysis, and analysis of α-diversity and β-diversity.RESULTS: The rat model of FD was successfully established using the tail-clamping stimulation method. The statistical results of cluster analysis of operational taxonomic units(OTUs) showed that the relative abundance of OTUs in the FD group was the lowest, while it was the highest in the normal(N) group. The composition of microbiome in the four groups was similar at phyla level. Compared with the FD group, the abundance of Firmicutes was downregulated, and the abundance of Proteobacteria and Bacteroidetes was upregulated in the Simo Tang(SMT) and high-dose Simo Tang(SMT.G) groups. The ratio of Bacteroidetes/Firmicutes was also elevated. According to the analysis of α-diversity and β-diversity, the abundance of flora in FD rats was significantly reduced. The treatment using SMT appeared beneficial to improve the diversity of flora. SMT could improve the intestinal flora in FD rats. The results showed that FD rats had intestinal flora imbalance, and species diversity increased. The results suggested that SMT could regulate the disorders of intestinal flora caused by FD. CONCLUDIONS: SMT could restore gut homeostasis and maintain gut flora diversity by modulating the gut microbiota and its associated metabolites in rats, thereby treating gastrointestinal diseases.展开更多
Objective Evidence suggests that depleted gut microbialα-diversity is associated with hypertension;however,whether metabolic markers affect this relationship remains unknown.We aimed to determine the potential metabo...Objective Evidence suggests that depleted gut microbialα-diversity is associated with hypertension;however,whether metabolic markers affect this relationship remains unknown.We aimed to determine the potential metabolites mediating the associations ofα-diversity with blood pressure(BP)and BP variability(BPV).Methods Metagenomics and plasma targeted metabolomics were conducted on 523 Chinese participants from the MetaSalt study.The 24-hour,daytime,and nighttime BP and BPV were calculated based on ambulatory BP measurements.Linear mixed models were used to characterize the relationships betweenα-diversity(Shannon and Chao1 index)and BP indices.Mediation analyses were performed to assess the contribution of metabolites to the observed associations.The influence of key metabolites on hypertension was further evaluated in a prospective cohort of 2,169 participants.Results Gut microbial richness(Chao1)was negatively associated with 24-hour systolic BP,daytime systolic BP,daytime diastolic BP,24-hour systolic BPV,and nighttime systolic BPV(P<0.05).Moreover,26 metabolites were strongly associated with richness(Bonferroni P<0.05).Among them,four key metabolites(imidazole propionate,2-hydroxy-3-methylbutyric acid,homovanillic acid,and hydrocinnamic acid)mediated the associations between richness and BP indices(proportions of mediating effects:14.1%–67.4%).These key metabolites were also associated with hypertension in the prospective cohort.For example,each 1-standard deviation unit increase in hydrocinnamic acid significantly reduced the risk of prevalent(OR[95%CI]=0.90[0.82,0.99];P=0.03)and incident hypertension(HR[95%CI]=0.83[0.71,0.96];P=0.01).Conclusion Our results suggest that gut microbial richness correlates with lower BP and BPV,and that certain metabolites mediate these associations.These findings provide novel insights into the pathogenesis and prevention of hypertension.展开更多
Liver transplantation is a conventional treatment for terminal stage liver diseases. However, several complications still hinder the survival rate. Intestinal barrier destruction is widely observed among patients rece...Liver transplantation is a conventional treatment for terminal stage liver diseases. However, several complications still hinder the survival rate. Intestinal barrier destruction is widely observed among patients receiving liver transplant and suffering from ischemia-reperfusion or rejection injuries because of the relationship between the intestine and the fiver, both in anatomy and function. Importantly, the resulting alteration of gut microbiota aggravates graft dysfunctions during the process. This article reviews the research progress for gut microbial alterations and liver transplantation. Especially, this work also evaluates research on the management of gut microbial alteration and the prediction of possible injuries utilizing microbial alteration during liver transplantation. In addition, we propose possible directions for research on gut microbial alteration during liver transplantation and offer a hypothesis on the utilization of microbial alteration in liver transplantation. The aim is not only to predict perioperative injuries but also to function as a method of treatment or even inhibit the rejection of liver transplantation.展开更多
Lepidium meyenii Walp.is a type of food used to fight fatigue,and macamides is the key anti-fatigue component in Lepidium meyenii Walp.water extract(Maca).The mechanisms of action of several foods with anti-fatigue pr...Lepidium meyenii Walp.is a type of food used to fight fatigue,and macamides is the key anti-fatigue component in Lepidium meyenii Walp.water extract(Maca).The mechanisms of action of several foods with anti-fatigue properties lie in the oxidative balance of tissues;however,little attention has been given to the microbiome.The gut microbial community is closely related to dietary choices,as well as exercise-induced skeletal muscle fatigue.As such,this study used a foodomics approach to analyze the anti-fatigue properties of maca amide,a key component in maca,on the gut microbiome.The key components in maca were identified,and after validation in a mouse model,an analysis of the gut microbiome was performed.The results of database searches and network analyses showed that the key anti-fatigue component of maca was N-benzyl-9Z,12Z-octadecadienamide(Mm).Further analyses revealed that the key microbes metabolizing Mm belonged to Alistipes,Alloprevotella,Parabacteroides,and Butyricimonas genera and the Prevotellaceae in mice.The results of microbial analysis showed that Mm could improve exercise-induced skeletal muscle fatigue in mice by modulating the L-glutamate-ornithine-proline axis through the breakdown of histidine,arginine,and proline.Therefore,from foodomics and gut microbial genomics perspectives,this study demonstrates that macamide is the key anti-fatigue component in maca,and these findings provide new insights for the development of foods that fight fatigue.展开更多
Association networks are widely applied for the prediction of bacterial interactions in studies of human gut microbiomes.However,the experimental validation of the predicted interactions is challenging due to the comp...Association networks are widely applied for the prediction of bacterial interactions in studies of human gut microbiomes.However,the experimental validation of the predicted interactions is challenging due to the complexity of gut microbiomes and the limited number of cultivated bacteria.In this study,we addressed this challenge by integrating in vitro time series network(TSN)associations and cocultivation of TSN taxon pairs.Fecal samples were collected and used for cultivation and enrichment of gut microbiome on YCFA agar plates for 13 days.Enriched cells were harvested for DNA extraction and metagenomic sequencing.A total of 198 metagenome-assembled genomes(MAGs)were recovered.Temporal dynamics of bacteria growing on the YCFA agar were used to infer microbial association networks.To experimentally validate the interactions of taxon pairs in networks,we selected 24 and 19 bacterial strains from this study and from the previously established human gut microbial biobank,respectively,for pairwise co-cultures.The co-culture experiments revealed that most of the interactions between taxa in networks were identified as neutralism(51.67%),followed by commensalism(21.67%),amensalism(18.33%),competition(5%)and exploitation(3.33%).Genome-centric analysis further revealed that the commensal gut bacteria(helpers and beneficiaries)might interact with each other via the exchanges of amino acids with high biosynthetic costs,short-chain fatty acids,and/or vitamins.We also validated 12 beneficiaries by adding 16 additives into the basic YCFA medium and found that the growth of 66.7%of these strains was significantly promoted.This approach provides new insights into the gut microbiome complexity and microbial interactions in association networks.Our work highlights that the positive relationships in gut microbial communities tend to be overestimated,and that amino acids,short-chain fatty acids,and vitamins are contributed to the positive relationships.展开更多
Chronic diarrhea remains a frequent and debilitating complication among individuals living with HIV,particularly in the context of advanced immunosuppression.Its multifactorial nature often complicates both diagnosis ...Chronic diarrhea remains a frequent and debilitating complication among individuals living with HIV,particularly in the context of advanced immunosuppression.Its multifactorial nature often complicates both diagnosis and treatment.We present insights from our recent study investigating gut microbial alterations using 16S rRNA sequencing in HIV-positive patients with diarrheal syndrome of unclear etiology.展开更多
Objectives:Colorectal cancer(CRC)is one of the most common cancers all over the world.The progression of CRC is associated with inflammation and disruptions in intestinal flora.3-O-Acetyl-11-keto-β-boswellic acid(AKB...Objectives:Colorectal cancer(CRC)is one of the most common cancers all over the world.The progression of CRC is associated with inflammation and disruptions in intestinal flora.3-O-Acetyl-11-keto-β-boswellic acid(AKBA)has been noted for its potent anti-inflammatory properties.However,the effect of AKBA on colon cancer caused by inflammation and its mechanism are not unclear.The study is to explore the effect of AKBA on CRC and its mechanism.Materials and Methods:Cell proliferation,(5-ethynyl-2′-deoxyuridine,EdU)-DNA synthesis assay and colony formation were used to assess the effect of AKBA on the proliferation of CRC cells.Flow cytometry was employed to analyze the cell cycle and apoptosis rate of cells treated with AKBA.RNA sequencing was done to explore the underlying mechanisms of AKBA.Western blot was used to assess the expression of key proteins in the nuclear factor kappa-B(NF-κB)signaling pathway after the treatment of AKBA.Real-time quantitative PCR(RT-qPCR),enzyme-linked immunosorbent assay(ELISA),and Meso Scale Discovery(MSD)assays were employed to check the anti-inflammation effects of AKBA on Lipopolysaccharide(LPS)-induced RAW264.7 cells and LPS-induced mouse model.Additionally,the Azoxymethane/Dextran sulfate sodium(AOM/DSS)-induced colitis-associated CRC model was used to evaluate the anti-CRC effect of AKBA.Gut microbiota profiling of fecal samples from CRC mice,both with and without AKBA treatment,was conducted through metagenomic sequencing analysis.Results:Our results showed that AKBA reduced the proliferation of HCT116 and SW620 cells,increased apoptosis of cells,and arrested the cell cycle at the G2/M phase.Results from RNA-seq showed that AKBA inhibited CRC by inhibiting the NF-κB signaling pathway and reducing cellular inflammation.Furthermore,AKBA reduced the levels of inflammatory cytokines,including tumor necrosis factor-α(TNF-α),Interferon-γ(IFN-γ),Interleukin-IL-12p70(IL-12p70),Interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)in both the spleen and serum of LPS-induced acute inflammation mice.Additionally,AKBA inhibited the development of AOM/DSS-induced colitis-associated colon cancer in mice and positively influenced gut microbiota.Conclusion:This study highlights the inhibitory effect of AKBA on colitis-associated CRC and reveals a novel aspect of its role in the remodeling of gut microbiota.These findings suggest that AKBA may be used as a potential therapeutic agent for CRC.展开更多
The human microbiota is an aggregate of microorganisms residing in the human body, mostly in the gastrointestinal tract （GIT）. Our gut microbiota evolves with us and plays a pivotal role in human health and disease....The human microbiota is an aggregate of microorganisms residing in the human body, mostly in the gastrointestinal tract （GIT）. Our gut microbiota evolves with us and plays a pivotal role in human health and disease. In recent years, the microbiota has gained increasing attention due to its impact on host metabolism, physiology, and immune system development, but also because the perturbation of the microbiota may result in a number of diseases. The gut microbiota may be linked to malignancies such as gastric cancer and colorectal cancer. It may also be linked to disorders such as nonalcoholic fatty liver disease （NAFLD）; obesity and diabetes, which are characterized as ＂lifestyle diseases＂ of the industrial- ized world; coronary heart disease; and neurological disorders. Although the revolution in molecular technologies has provided us with the necessary tools to study the gut microbiota more accurately, we need to elucidate the relationships between the gut microbiota and several human pathologies more precisely, as understanding the impact that the microbiota plays in various diseases is fundamental for the development of novel therapeutic strategies. Therefore, the aim of this review is to provide the read- er with an updated overview of the importance of the gut microbiota for human health and the poten- tial to manipulate gut microbial composition for purposes such as the treatment of antibiotic-resistant Clostridium difficile （C difficile） infections. The concept of altering the gut community by microbial intervention in an effort to improve health is currently in its infancy. However, the therapeutic implications appear to be very great. Thus, the removal of harmful organisms and the enrichment of beneficial mi- crobes may protect our health, and such efforts will pave the way for the development of more rational treatment options in the future.展开更多
Bee pollen has potential in preventing metabolic syndrome(MetS).The present study aimed to investigate the effect of yeast-fermented wall-broken bee pollen(YB)intervention on ICR mice with MetS induced with a high-fat...Bee pollen has potential in preventing metabolic syndrome(MetS).The present study aimed to investigate the effect of yeast-fermented wall-broken bee pollen(YB)intervention on ICR mice with MetS induced with a high-fat(HF)diet.After YB intervention in mice for 16 weeks,the effect on alleviating MetS was evaluated based on MetS serum parameters,hepatic oxidant status markers and gut microbial populations.The results of animal experiment showed that YB intervention attenuated MetS.Based on multivariate statistical analysis results,YB treatment signifi cantly increased glutathione S-transferase(GST)and catalase(CAT)activities and decreased the malondialdehyde(MDA)level in the liver.Further investigation showed that YB restored the Nrf-2-Keap-1 pathway to alleviate oxidative stress.Additionally,gut microbial community analysis revealed that YB restored the increase in the Firmicutes to Bacteroidetes(F/B)ratio(6.94 for the HF group and 3.74 for HF+YB group)and improved Lactobacillus and Lactococcus abundance induced by the HF diet.Overall,YB improved function and prevented MetS by modulating the gut microbiota and alleviating oxidative stress.展开更多
BACKGROUND The gut microbiota is strongly associated with radiation-induced gut damage.This study aimed to assess the effectiveness and safety of intestinal microecological transplantation for treating patients with c...BACKGROUND The gut microbiota is strongly associated with radiation-induced gut damage.This study aimed to assess the effectiveness and safety of intestinal microecological transplantation for treating patients with chronic radiation enteritis.CASE SUMMARY A 64-year-old female with cervical cancer developed abdominal pain,diarrhea,and blood in the stool 1 year after radiotherapy.An electronic colonoscopy was performed to diagnose chronic radiation enteritis.Two courses of intestinal microecological transplantation and full-length 16S rRNA microbiological analysis were performed.The patient experienced short-and long-term relief from symptoms without adverse effects.Whole 16S rRNA sequencing revealed significant differences in the intestinal flora’s composition between patient and healthy donors.Pathogenic bacteria,such as Escherichia fergusonii and Romboutsia timonensis,were more in the patient.Beneficial bacteria such as Faecalibacterium prausnitzii,Fusicatenibacter saccharivorans,Ruminococcus bromii,and Bifidobacterium longum were more in the healthy donors.Intestinal microbiota transplantation resulted in a significant change in the patient's intestinal flora composition.The composition converged with the donor's flora,with an increase in core beneficial intestinal bacteria,such as Eubacterium rectale,and a decrease in pathogenic bacteria.Changes in the intestinal flora corresponded with the patients'alleviating clinical symptoms.CONCLUSION Intestinal microecological transplantation is an effective treatment for relieving the clinical symptoms of chronic radiation enteritis by altering the composition of the intestinal flora.This study provides a new approach for treating patients with chronic radiation enteritis.展开更多
Psychological stress causes gut microbial dysbiosis and cancer progression,yet how gut microbiota determines psychological stressinduced tumor development remains unclear.Here we showed that psychological stress promo...Psychological stress causes gut microbial dysbiosis and cancer progression,yet how gut microbiota determines psychological stressinduced tumor development remains unclear.Here we showed that psychological stress promotes breast tumor growth and cancer stemness,an outcome that depends on gut microbiota in germ-free and antibiotic-treated mice.Metagenomic and metabolomic analyses revealed that psychological stress markedly alters the composition and abundance of gut microbiota,especially Akkermansia muciniphila(A.muciniphila),and decreases short-chain fatty acid butyrate.Supplement of active A.muciniphila,butyrate or a butyrateproducing high fiber diet dramatically reversed the oncogenic property and anxiety-like behavior of psychological stress in a murine spontaneous tumor model or an orthotopic tumor model.Mechanistically,RNA sequencing analysis screened out that butyrate decreases LRP5 expression to block the activation of Wnt/β-catenin signaling pathway,dampening breast cancer stemness.Moreover,butyrate as a HDAC inhibitor elevated histone H3K9 acetylation level to transcriptionally activate ZFP36,which further accelerates LRP5 mRNA decay by binding adenine uridine-rich(AU-rich)elements of LRP5 transcript.Clinically,fecal A.muciniphila and serum butyrate were inversely correlated with tumoral LRP5/β-catenin expression,poor prognosis and negative mood in breast cancer patients.Altogether,our findings uncover a microbiota-dependent mechanism of psychological stress-triggered cancer stemness,and provide both clinical biomarkers and potential therapeutic avenues for cancer patients undergoing psychological stress.展开更多
The gut has been a focal point in the research of digestive system disorders.The internal microbiota generates metabolites that function as signaling molecules and substrates,interacting with the intestinal wall and i...The gut has been a focal point in the research of digestive system disorders.The internal microbiota generates metabolites that function as signaling molecules and substrates,interacting with the intestinal wall and influ-encing host physiology and pathology.Besides,the gut microbiota and metabolites owe highly diverse types and quantities,posing challenges for quantitative analysis,and monitoring frequent interactions between diges-tive tract metabolites and the intestinal wall remains a challenge.However,research targeting gut microbiota metabolites has elucidated their relevance to digestive diseases.By modulating metabolites such as short-chain fatty acids,bile acids,and lipopolysaccharides,it is possible to intervene in the progression of diseases such as inflammatory bowel disease and non-alcoholic fatty liver disease.Currently,research on gut microbiota is advancing,and more work is required to explore the interactions between host,microbes and underlying mech-anisms.In this review,we have revisited the generation of gut microbiota-related metabolites,their impact on diseases,and modes of interaction,emphasizing the significant role of metabolites in digestive system disorders.It is believed that the linkage between gut microbiota and diseases in current research can be established through metabolites,providing a framework and foundation for research in the field of metabolomics and fundamental mechanisms.展开更多
As the significance of the gut microbiota has become increasingly realized,a large number of related studies have emerged.With respect to the gut microbial composition of fish,the predominant gut microbes and core gut...As the significance of the gut microbiota has become increasingly realized,a large number of related studies have emerged.With respect to the gut microbial composition of fish,the predominant gut microbes and core gut microbiota have been reported by many researchers.Our understanding of fish gut microbiota,especially its functional roles,has fallen far behind that of terrestrial vertebrates,although previous studies using gnotobiotic zebrafish models have revealed that the gut microbiota performs a significant role in gut development,nutrient metabolism and immune responses.Given that environmental factors of marine habitats are very different from those of freshwater habitats,a distinct difference may exist in the gut microbiota between freshwater and marine fish.Therefore,this review aims to address the advances in marine fish gut microbiota in terms of methodologies,the gut microbial composition,and gnotobiotic models of marine fish,the important factors(host genotype and three environmental factors:temperature,salinity and diet)that drive marine fish gut microbiota,and significant roles of the gut microbiota in marine fish.展开更多
Multilevel society is one of the most complex social systems in natural ecosystems and is a typical feature among some primates.Given the potential connection between social behavior and gut microbiome composition,the...Multilevel society is one of the most complex social systems in natural ecosystems and is a typical feature among some primates.Given the potential connection between social behavior and gut microbiome composition,the multilevel social system could affect the primate gut microbiome.Here,based on long-term observation(e.g.social unit dynamics,transfer,and behavior),we investigated this potential integrating 16S rRNA gene amplicon sequencing and behavior data in Yunnan snub-nosed monkeys(Rhinopithecus bieti),which possess a multilevel social group based on one male units(OMUs,each unit with several breeding females and their offspring)and all-male unit(AMU,several bachelor males residing together).We found that the mean unweighted Unifrac distance between adult males from different OMUs was significantly lower than that between adult females from different OMUs(paired Wilcoxon test,P=0.007).There was no significant difference in the mean unweighted Unifrac distance between females within the same OMU or between females from different OMUs.These findings indicated the potential connection between the defense and invasion of social units and the gut microbiome community in wild Yunnan snub-nosed monkeys.We speculated that the resident males of OMUs displaying a significantly higher similarity in the gut microbial community than that of adult females in separate OMUs might be associated with the sexual differences in their interactions and from previously having cohabitated together in the AMU.Therefore,this study suggested that multilevel societies might have an effect on the gut microbial community in this wild nonhuman primate species.展开更多
基金Supported by National Natural Science Foundation of China,No.81273919 and No.81673727National Basic Research Program of China(973 Program)No.2013CB531703
文摘AIM To investigate gut microbial diversity and the interventional effect of Xiaoyaosan(XYS) in a rat model of functional dyspepsia(FD) with liver depression-spleen deficiency syndrome. METHODS The FD with liver depression-spleen deficiency syndrome rat model was established through classic chronic mild unpredictable stimulation every day. XYS group rats received XYS 1 h before the stimulation. The models were assessed by parameters including state ofthe rat, weight, sucrose test result and open-field test result. After 3 wk, the stools of rats were collected and genomic DNA was extracted. PCR products of the V4 region of 16 S rD NA were sequenced using a barcoded Illumina paired-end sequencing technique. The primary composition of the microbiome in the stool samples was determined and analyzed by cluster analysis.RESULTS Rat models were successfully established, per data from rat state, weight and open-field test. The microbiomes contained 20 phyla from all samples. Firmicutes, Bacteroidetes, Proteobacteria, Cyanobacteria and Tenericutes were the most abundant taxonomic groups. The relative abundance of Firmicutes, Proteobacteria and Cyanobacteria in the model group was higher than that in the normal group. On the contrary, the relative abundance of Bacteroidetes in the model group was lower than that in the normal group. Upon XYS treatment, the relative abundance of all dysregulated phyla was restored to levels similar to those observed in the normal group. Abundance clustering heat map of phyla corroborated the taxonomic distribution. CONCLUSION The microbiome relative abundance of FD rats with liver depression-spleen deficiency syndrome was significantly different from the normal cohort. XYS intervention may effectively adjust the gut dysbacteriosis in FD.
基金supported by the National Natural Science Foundation of China (91857101)the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB29020000)the National Key Research and Development Program of China (2018YFC2000500)
文摘The gut-liver axis denotes the intricate connection and interaction between gut microbiome and liver, in which compositional and functional shifts in gut microbiome affect host metabolism. Hepatic portal vein of the blood circulation system has been thought to be the major route for metabolite transportation in the gut-liver axis, but the existence and importance of other routes remain elusive. Here, we perform metabolome comparison in blood circulation and mesenteric lymph systems and identify significantly shifted metabolites in serum and mesentery. Using cellular assays, we find that the majority of decreased metabolites in lymph system under high-fat diet are effective in alleviating metabolic disorders, indicating a high potential of lymph system in regulating liver metabolism. Among those, a representative metabolite, L-carnitine, reduces diet-induced obesity in mice. Metabolic tracing analysis identifies that L-carnitine is independently transported by the mesenteric lymph system, serving as an example that lymph circulation comprises a second route in the gut-liver axis to modulate liver metabolism. Our study provides new insights into metabolite transportation via mesenteric lymph system in the gut-liver axis, offers an extended scope for the investigations in host-gut microbiota metabolic interactions and potentially new targets in the treatment of metabolic disorders.
基金Supported by the University Scientific Research Projects of Anhui,No. KJ2020A0401 and 2022AH050491the open fund of the Ministry of Education Key Laboratory of Glucolipid Metabolic Disorder,No. GYDKFXM01+5 种基金the Anhui University Collaborative Innovation Project,No. GXXT-2020-025the National Natural Science Foundation of China,No. 82174153the National Key Research and Development Program,No. 2018YFC1704202the Anhui Provincial Quality Engineering Project of Universities,No. 2021jyxm0834the Major and Difficult Diseases Project of Anhui Province,No. 2021zdynjb06the Clinical Research Project of Anhui University of Traditional Chinese Medicine,No. 2021yfylc01
文摘BACKGROUND In recent years,the incidence of type 2 diabetes(T2DM)has shown a rapid growth trend.Goto Kakizaki(GK)rats are a valuable model for the study of T2DM and share common glucose metabolism features with human T2DM patients.A series of studies have indicated that T2DM is associated with the gut microbiota composition and gut metabolites.We aimed to systematically characterize the faecal gut microbes and metabolites of GK rats and analyse the relationship between glucose and insulin resistance.AIM To evaluate the gut microbial and metabolite alterations in GK rat faeces based on metagenomics and untargeted metabolomics.METHODS Ten GK rats(model group)and Wistar rats(control group)were observed for 10 wk,and various glucose-related indexes,mainly including weight,fasting blood glucose(FBG)and insulin levels,homeostasis model assessment of insulin resistance(HOMA-IR)and homeostasis model assessment ofβcell(HOMA-β)were assessed.The faecal gut microbiota was sequenced by metagenomics,and faecal metabolites were analysed by untargeted metabolomics.Multiple metabolic pathways were evaluated based on the differential metabolites identified,and the correlations between blood glucose and the gut microbiota and metabolites were analysed.RESULTS The model group displayed significant differences in weight,FBG and insulin levels,HOMA-IR and HOMA-βindexes(P<0.05,P<0.01)and a shift in the gut microbiota structure compared with the control group.The results demonstrated significantly decreased abundances of Prevotella sp.CAG:604 and Lactobacillus murinus(P<0.05)and a significantly increased abundance of Allobaculum stercoricanis(P<0.01)in the model group.A correlation analysis indicated that FBG and HOMA-IR were positively correlated with Allobaculum stercoricanis and negatively correlated with Lactobacillus murinus.An orthogonal partial least squares discriminant analysis suggested that the faecal metabolic profiles differed between the model and control groups.Fourteen potential metabolic biomarkers,including glycochenodeoxycholic acid,uric acid,13(S)-hydroxyoctadecadienoic acid(HODE),N-acetylaspartate,β-sitostenone,sphinganine,4-pyridoxic acid,and linoleic acid,were identified.Moreover,FBG and HOMA-IR were found to be positively correlated with glutathione,13(S)-HODE,uric acid,4-pyridoxic acid and allantoic acid and negatively correlated with 3-α,7-α,chenodeoxycholic acid glycine conjugate and 26-trihydroxy-5-β-cholestane(P<0.05,P<0.01).Allobaculum stercoricanis was positively correlated with linoleic acid and sphinganine(P<0.01),and 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate was negatively associated with Prevotella sp.CAG:604(P<0.01).The metabolic pathways showing the largest differences were arginine biosynthesis;primary bile acid biosynthesis;purine metabolism;linoleic acid metabolism;alanine,aspartate and glutamate metabolism;and nitrogen metabolism.CONCLUSION Metagenomics and untargeted metabolomics indicated that disordered compositions of gut microbes and metabolites may be common defects in GK rats.
基金National Natural Science Foundation of China:Changes of Ras Homolog Gene Family Member A/Rho-associated Coiled-coil Kinase Signaling Pathway in Liver-Stomach Disharmony Functional Dyspepsia Rats and Intervention Mechanism of Simo Tang (No. 81803896)the Role of Gut Microbiota-diaminopimelic Acid Nucleotide-binding and Oligomerization Domain1-receptorinteracting Protein 2 Signal Pathway in Severe Process of Acute Pancreatitis and the Intervention Mechanism of Qingxia Therapy (No. 81873156)Research Project of Liaoning Provincial Department of Education:the Role of Mitochondria-Derived Reactive Oxygen Species Mediated Autophagy Activation in Myocardial Injury in Sepsis (No. LZ2020036)。
文摘OBJECTIVE: To investigate composition of gut microbial community in a rat model of functional dyspepsia(FD) and to explore the interventional effects of Simo Tang(四磨汤, SMT). METHODS: A rat model of FD was established through the tail-clamping stimulation method. The rat model of FD was assessed by the state of rats, their weight, sucrose preference rate, and intestinal propulsion rate. The DNA was extracted from stool samples after treatment with SMT. Amplified polymerase chain reaction(PCR) products of the 16S r DNA were sequenced using Novase Q6000 after construction of libraries. Composition of gut microbial community in the stool samples was determined and analyzed by cluster analysis, bioinformatic analysis, and analysis of α-diversity and β-diversity.RESULTS: The rat model of FD was successfully established using the tail-clamping stimulation method. The statistical results of cluster analysis of operational taxonomic units(OTUs) showed that the relative abundance of OTUs in the FD group was the lowest, while it was the highest in the normal(N) group. The composition of microbiome in the four groups was similar at phyla level. Compared with the FD group, the abundance of Firmicutes was downregulated, and the abundance of Proteobacteria and Bacteroidetes was upregulated in the Simo Tang(SMT) and high-dose Simo Tang(SMT.G) groups. The ratio of Bacteroidetes/Firmicutes was also elevated. According to the analysis of α-diversity and β-diversity, the abundance of flora in FD rats was significantly reduced. The treatment using SMT appeared beneficial to improve the diversity of flora. SMT could improve the intestinal flora in FD rats. The results showed that FD rats had intestinal flora imbalance, and species diversity increased. The results suggested that SMT could regulate the disorders of intestinal flora caused by FD. CONCLUDIONS: SMT could restore gut homeostasis and maintain gut flora diversity by modulating the gut microbiota and its associated metabolites in rats, thereby treating gastrointestinal diseases.
基金supported by the National Science and Technology Major Program for Noncommunicable Chronic Diseases(2023ZD0503500)the National Natural Science Foundation of China(82030102,12126602,91857118)+1 种基金the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2M-1-010,2019-I2M-2-003)the National High Level Hospital Clinical Research Funding(2022-GSP-GG-1,2022-GSP-GG-2)。
文摘Objective Evidence suggests that depleted gut microbialα-diversity is associated with hypertension;however,whether metabolic markers affect this relationship remains unknown.We aimed to determine the potential metabolites mediating the associations ofα-diversity with blood pressure(BP)and BP variability(BPV).Methods Metagenomics and plasma targeted metabolomics were conducted on 523 Chinese participants from the MetaSalt study.The 24-hour,daytime,and nighttime BP and BPV were calculated based on ambulatory BP measurements.Linear mixed models were used to characterize the relationships betweenα-diversity(Shannon and Chao1 index)and BP indices.Mediation analyses were performed to assess the contribution of metabolites to the observed associations.The influence of key metabolites on hypertension was further evaluated in a prospective cohort of 2,169 participants.Results Gut microbial richness(Chao1)was negatively associated with 24-hour systolic BP,daytime systolic BP,daytime diastolic BP,24-hour systolic BPV,and nighttime systolic BPV(P<0.05).Moreover,26 metabolites were strongly associated with richness(Bonferroni P<0.05).Among them,four key metabolites(imidazole propionate,2-hydroxy-3-methylbutyric acid,homovanillic acid,and hydrocinnamic acid)mediated the associations between richness and BP indices(proportions of mediating effects:14.1%–67.4%).These key metabolites were also associated with hypertension in the prospective cohort.For example,each 1-standard deviation unit increase in hydrocinnamic acid significantly reduced the risk of prevalent(OR[95%CI]=0.90[0.82,0.99];P=0.03)and incident hypertension(HR[95%CI]=0.83[0.71,0.96];P=0.01).Conclusion Our results suggest that gut microbial richness correlates with lower BP and BPV,and that certain metabolites mediate these associations.These findings provide novel insights into the pathogenesis and prevention of hypertension.
文摘Liver transplantation is a conventional treatment for terminal stage liver diseases. However, several complications still hinder the survival rate. Intestinal barrier destruction is widely observed among patients receiving liver transplant and suffering from ischemia-reperfusion or rejection injuries because of the relationship between the intestine and the fiver, both in anatomy and function. Importantly, the resulting alteration of gut microbiota aggravates graft dysfunctions during the process. This article reviews the research progress for gut microbial alterations and liver transplantation. Especially, this work also evaluates research on the management of gut microbial alteration and the prediction of possible injuries utilizing microbial alteration during liver transplantation. In addition, we propose possible directions for research on gut microbial alteration during liver transplantation and offer a hypothesis on the utilization of microbial alteration in liver transplantation. The aim is not only to predict perioperative injuries but also to function as a method of treatment or even inhibit the rejection of liver transplantation.
基金supported by the National Key Research and Development Program of China(Nos.2020YFC1606800).
文摘Lepidium meyenii Walp.is a type of food used to fight fatigue,and macamides is the key anti-fatigue component in Lepidium meyenii Walp.water extract(Maca).The mechanisms of action of several foods with anti-fatigue properties lie in the oxidative balance of tissues;however,little attention has been given to the microbiome.The gut microbial community is closely related to dietary choices,as well as exercise-induced skeletal muscle fatigue.As such,this study used a foodomics approach to analyze the anti-fatigue properties of maca amide,a key component in maca,on the gut microbiome.The key components in maca were identified,and after validation in a mouse model,an analysis of the gut microbiome was performed.The results of database searches and network analyses showed that the key anti-fatigue component of maca was N-benzyl-9Z,12Z-octadecadienamide(Mm).Further analyses revealed that the key microbes metabolizing Mm belonged to Alistipes,Alloprevotella,Parabacteroides,and Butyricimonas genera and the Prevotellaceae in mice.The results of microbial analysis showed that Mm could improve exercise-induced skeletal muscle fatigue in mice by modulating the L-glutamate-ornithine-proline axis through the breakdown of histidine,arginine,and proline.Therefore,from foodomics and gut microbial genomics perspectives,this study demonstrates that macamide is the key anti-fatigue component in maca,and these findings provide new insights for the development of foods that fight fatigue.
基金supported by the National Key Research and Development Program of China(2021YFA0717002)Taishan Young Scholars(tsqn202306029).
文摘Association networks are widely applied for the prediction of bacterial interactions in studies of human gut microbiomes.However,the experimental validation of the predicted interactions is challenging due to the complexity of gut microbiomes and the limited number of cultivated bacteria.In this study,we addressed this challenge by integrating in vitro time series network(TSN)associations and cocultivation of TSN taxon pairs.Fecal samples were collected and used for cultivation and enrichment of gut microbiome on YCFA agar plates for 13 days.Enriched cells were harvested for DNA extraction and metagenomic sequencing.A total of 198 metagenome-assembled genomes(MAGs)were recovered.Temporal dynamics of bacteria growing on the YCFA agar were used to infer microbial association networks.To experimentally validate the interactions of taxon pairs in networks,we selected 24 and 19 bacterial strains from this study and from the previously established human gut microbial biobank,respectively,for pairwise co-cultures.The co-culture experiments revealed that most of the interactions between taxa in networks were identified as neutralism(51.67%),followed by commensalism(21.67%),amensalism(18.33%),competition(5%)and exploitation(3.33%).Genome-centric analysis further revealed that the commensal gut bacteria(helpers and beneficiaries)might interact with each other via the exchanges of amino acids with high biosynthetic costs,short-chain fatty acids,and/or vitamins.We also validated 12 beneficiaries by adding 16 additives into the basic YCFA medium and found that the growth of 66.7%of these strains was significantly promoted.This approach provides new insights into the gut microbiome complexity and microbial interactions in association networks.Our work highlights that the positive relationships in gut microbial communities tend to be overestimated,and that amino acids,short-chain fatty acids,and vitamins are contributed to the positive relationships.
文摘Chronic diarrhea remains a frequent and debilitating complication among individuals living with HIV,particularly in the context of advanced immunosuppression.Its multifactorial nature often complicates both diagnosis and treatment.We present insights from our recent study investigating gut microbial alterations using 16S rRNA sequencing in HIV-positive patients with diarrheal syndrome of unclear etiology.
基金financially supported by Beijing Natural Science Foundation[7252202,25JL008,China]from Beijing Natural Science Foundation CommitteeThis work was also supported by CAMS Innovation Fund for Medical Sciences[2021-I2M-1-029,2023-12M-2-006,China]and[2021-I2M-1-028,China]from Chinese Academy of Medical Science&Peking Union Medical College(CAMS&PUMC)+1 种基金National Natural Science Foundation of China[81703536 and 22278443,China]from Natural Science Foundation CommitteeInternational Cooperation Project of Qinghai Province[2020-HZ-803,China]from Science and Technology Department of Qinghai Province.
文摘Objectives:Colorectal cancer(CRC)is one of the most common cancers all over the world.The progression of CRC is associated with inflammation and disruptions in intestinal flora.3-O-Acetyl-11-keto-β-boswellic acid(AKBA)has been noted for its potent anti-inflammatory properties.However,the effect of AKBA on colon cancer caused by inflammation and its mechanism are not unclear.The study is to explore the effect of AKBA on CRC and its mechanism.Materials and Methods:Cell proliferation,(5-ethynyl-2′-deoxyuridine,EdU)-DNA synthesis assay and colony formation were used to assess the effect of AKBA on the proliferation of CRC cells.Flow cytometry was employed to analyze the cell cycle and apoptosis rate of cells treated with AKBA.RNA sequencing was done to explore the underlying mechanisms of AKBA.Western blot was used to assess the expression of key proteins in the nuclear factor kappa-B(NF-κB)signaling pathway after the treatment of AKBA.Real-time quantitative PCR(RT-qPCR),enzyme-linked immunosorbent assay(ELISA),and Meso Scale Discovery(MSD)assays were employed to check the anti-inflammation effects of AKBA on Lipopolysaccharide(LPS)-induced RAW264.7 cells and LPS-induced mouse model.Additionally,the Azoxymethane/Dextran sulfate sodium(AOM/DSS)-induced colitis-associated CRC model was used to evaluate the anti-CRC effect of AKBA.Gut microbiota profiling of fecal samples from CRC mice,both with and without AKBA treatment,was conducted through metagenomic sequencing analysis.Results:Our results showed that AKBA reduced the proliferation of HCT116 and SW620 cells,increased apoptosis of cells,and arrested the cell cycle at the G2/M phase.Results from RNA-seq showed that AKBA inhibited CRC by inhibiting the NF-κB signaling pathway and reducing cellular inflammation.Furthermore,AKBA reduced the levels of inflammatory cytokines,including tumor necrosis factor-α(TNF-α),Interferon-γ(IFN-γ),Interleukin-IL-12p70(IL-12p70),Interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)in both the spleen and serum of LPS-induced acute inflammation mice.Additionally,AKBA inhibited the development of AOM/DSS-induced colitis-associated colon cancer in mice and positively influenced gut microbiota.Conclusion:This study highlights the inhibitory effect of AKBA on colitis-associated CRC and reveals a novel aspect of its role in the remodeling of gut microbiota.These findings suggest that AKBA may be used as a potential therapeutic agent for CRC.
基金This work was supported by grants from the National Natural Science Foundation of China （21375144 and 21105115） and the National Basic Research Program of China （2012CB934004）.
文摘The human microbiota is an aggregate of microorganisms residing in the human body, mostly in the gastrointestinal tract （GIT）. Our gut microbiota evolves with us and plays a pivotal role in human health and disease. In recent years, the microbiota has gained increasing attention due to its impact on host metabolism, physiology, and immune system development, but also because the perturbation of the microbiota may result in a number of diseases. The gut microbiota may be linked to malignancies such as gastric cancer and colorectal cancer. It may also be linked to disorders such as nonalcoholic fatty liver disease （NAFLD）; obesity and diabetes, which are characterized as ＂lifestyle diseases＂ of the industrial- ized world; coronary heart disease; and neurological disorders. Although the revolution in molecular technologies has provided us with the necessary tools to study the gut microbiota more accurately, we need to elucidate the relationships between the gut microbiota and several human pathologies more precisely, as understanding the impact that the microbiota plays in various diseases is fundamental for the development of novel therapeutic strategies. Therefore, the aim of this review is to provide the read- er with an updated overview of the importance of the gut microbiota for human health and the poten- tial to manipulate gut microbial composition for purposes such as the treatment of antibiotic-resistant Clostridium difficile （C difficile） infections. The concept of altering the gut community by microbial intervention in an effort to improve health is currently in its infancy. However, the therapeutic implications appear to be very great. Thus, the removal of harmful organisms and the enrichment of beneficial mi- crobes may protect our health, and such efforts will pave the way for the development of more rational treatment options in the future.
基金This study was supported by the National Natural Science Foundation of China(No.31972628 and 31472155)a special fund(NYCYTX-43)the fund of the Beijing Laboratory for Food Quality and Safety,Beijing Technology and Business University.
文摘Bee pollen has potential in preventing metabolic syndrome(MetS).The present study aimed to investigate the effect of yeast-fermented wall-broken bee pollen(YB)intervention on ICR mice with MetS induced with a high-fat(HF)diet.After YB intervention in mice for 16 weeks,the effect on alleviating MetS was evaluated based on MetS serum parameters,hepatic oxidant status markers and gut microbial populations.The results of animal experiment showed that YB intervention attenuated MetS.Based on multivariate statistical analysis results,YB treatment signifi cantly increased glutathione S-transferase(GST)and catalase(CAT)activities and decreased the malondialdehyde(MDA)level in the liver.Further investigation showed that YB restored the Nrf-2-Keap-1 pathway to alleviate oxidative stress.Additionally,gut microbial community analysis revealed that YB restored the increase in the Firmicutes to Bacteroidetes(F/B)ratio(6.94 for the HF group and 3.74 for HF+YB group)and improved Lactobacillus and Lactococcus abundance induced by the HF diet.Overall,YB improved function and prevented MetS by modulating the gut microbiota and alleviating oxidative stress.
文摘BACKGROUND The gut microbiota is strongly associated with radiation-induced gut damage.This study aimed to assess the effectiveness and safety of intestinal microecological transplantation for treating patients with chronic radiation enteritis.CASE SUMMARY A 64-year-old female with cervical cancer developed abdominal pain,diarrhea,and blood in the stool 1 year after radiotherapy.An electronic colonoscopy was performed to diagnose chronic radiation enteritis.Two courses of intestinal microecological transplantation and full-length 16S rRNA microbiological analysis were performed.The patient experienced short-and long-term relief from symptoms without adverse effects.Whole 16S rRNA sequencing revealed significant differences in the intestinal flora’s composition between patient and healthy donors.Pathogenic bacteria,such as Escherichia fergusonii and Romboutsia timonensis,were more in the patient.Beneficial bacteria such as Faecalibacterium prausnitzii,Fusicatenibacter saccharivorans,Ruminococcus bromii,and Bifidobacterium longum were more in the healthy donors.Intestinal microbiota transplantation resulted in a significant change in the patient's intestinal flora composition.The composition converged with the donor's flora,with an increase in core beneficial intestinal bacteria,such as Eubacterium rectale,and a decrease in pathogenic bacteria.Changes in the intestinal flora corresponded with the patients'alleviating clinical symptoms.CONCLUSION Intestinal microecological transplantation is an effective treatment for relieving the clinical symptoms of chronic radiation enteritis by altering the composition of the intestinal flora.This study provides a new approach for treating patients with chronic radiation enteritis.
基金supported by the Science Fund for Creative Research Groups of the National Natural Science Foundation of China(82321003)the National Natural Science Foundation of China(82273480,82341020,82473131,82373096,82173361)+4 种基金National Key R&D Program of China(2022YFA1104002)Applied Basic Research Planning Project of Liaoning(2023JH2/101600019)Science and technology innovation team project of basic scientific research project of Liaoning Provincial Department of Education(LJ222410161065)the Science and Technology Talent Innovation Support Policy Implementation Program of Dalian-Outstanding young scientific and technological talents(2023RY013)the Shenzhen Bay Laboratory ResearchFunds(SZBL2021080601001toQL).
文摘Psychological stress causes gut microbial dysbiosis and cancer progression,yet how gut microbiota determines psychological stressinduced tumor development remains unclear.Here we showed that psychological stress promotes breast tumor growth and cancer stemness,an outcome that depends on gut microbiota in germ-free and antibiotic-treated mice.Metagenomic and metabolomic analyses revealed that psychological stress markedly alters the composition and abundance of gut microbiota,especially Akkermansia muciniphila(A.muciniphila),and decreases short-chain fatty acid butyrate.Supplement of active A.muciniphila,butyrate or a butyrateproducing high fiber diet dramatically reversed the oncogenic property and anxiety-like behavior of psychological stress in a murine spontaneous tumor model or an orthotopic tumor model.Mechanistically,RNA sequencing analysis screened out that butyrate decreases LRP5 expression to block the activation of Wnt/β-catenin signaling pathway,dampening breast cancer stemness.Moreover,butyrate as a HDAC inhibitor elevated histone H3K9 acetylation level to transcriptionally activate ZFP36,which further accelerates LRP5 mRNA decay by binding adenine uridine-rich(AU-rich)elements of LRP5 transcript.Clinically,fecal A.muciniphila and serum butyrate were inversely correlated with tumoral LRP5/β-catenin expression,poor prognosis and negative mood in breast cancer patients.Altogether,our findings uncover a microbiota-dependent mechanism of psychological stress-triggered cancer stemness,and provide both clinical biomarkers and potential therapeutic avenues for cancer patients undergoing psychological stress.
基金supported by Jiangsu Province Youth Fund project(BK20230142).
文摘The gut has been a focal point in the research of digestive system disorders.The internal microbiota generates metabolites that function as signaling molecules and substrates,interacting with the intestinal wall and influ-encing host physiology and pathology.Besides,the gut microbiota and metabolites owe highly diverse types and quantities,posing challenges for quantitative analysis,and monitoring frequent interactions between diges-tive tract metabolites and the intestinal wall remains a challenge.However,research targeting gut microbiota metabolites has elucidated their relevance to digestive diseases.By modulating metabolites such as short-chain fatty acids,bile acids,and lipopolysaccharides,it is possible to intervene in the progression of diseases such as inflammatory bowel disease and non-alcoholic fatty liver disease.Currently,research on gut microbiota is advancing,and more work is required to explore the interactions between host,microbes and underlying mech-anisms.In this review,we have revisited the generation of gut microbiota-related metabolites,their impact on diseases,and modes of interaction,emphasizing the significant role of metabolites in digestive system disorders.It is believed that the linkage between gut microbiota and diseases in current research can be established through metabolites,providing a framework and foundation for research in the field of metabolomics and fundamental mechanisms.
基金This work was financially supported by National Key R&D Program of China(No.2018YFD0900400)National Natural Science Foundation of China(Nos.31872577,41576137)China Agriculture Researches System(Grant No.CARS 47-G10).
文摘As the significance of the gut microbiota has become increasingly realized,a large number of related studies have emerged.With respect to the gut microbial composition of fish,the predominant gut microbes and core gut microbiota have been reported by many researchers.Our understanding of fish gut microbiota,especially its functional roles,has fallen far behind that of terrestrial vertebrates,although previous studies using gnotobiotic zebrafish models have revealed that the gut microbiota performs a significant role in gut development,nutrient metabolism and immune responses.Given that environmental factors of marine habitats are very different from those of freshwater habitats,a distinct difference may exist in the gut microbiota between freshwater and marine fish.Therefore,this review aims to address the advances in marine fish gut microbiota in terms of methodologies,the gut microbial composition,and gnotobiotic models of marine fish,the important factors(host genotype and three environmental factors:temperature,salinity and diet)that drive marine fish gut microbiota,and significant roles of the gut microbiota in marine fish.
基金support was provided by the National Natural Science Foundation of China(No.32070454)the Second Tibetan Plateau Scientific Expedition and Research Program(No.2019QZKK0501)+2 种基金the project of the National Key Programme of Research and Development,Ministry of Science and Technology(No.2016YFC0503200)Sichuan Science and Technology Program(2021JDRC0024)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘Multilevel society is one of the most complex social systems in natural ecosystems and is a typical feature among some primates.Given the potential connection between social behavior and gut microbiome composition,the multilevel social system could affect the primate gut microbiome.Here,based on long-term observation(e.g.social unit dynamics,transfer,and behavior),we investigated this potential integrating 16S rRNA gene amplicon sequencing and behavior data in Yunnan snub-nosed monkeys(Rhinopithecus bieti),which possess a multilevel social group based on one male units(OMUs,each unit with several breeding females and their offspring)and all-male unit(AMU,several bachelor males residing together).We found that the mean unweighted Unifrac distance between adult males from different OMUs was significantly lower than that between adult females from different OMUs(paired Wilcoxon test,P=0.007).There was no significant difference in the mean unweighted Unifrac distance between females within the same OMU or between females from different OMUs.These findings indicated the potential connection between the defense and invasion of social units and the gut microbiome community in wild Yunnan snub-nosed monkeys.We speculated that the resident males of OMUs displaying a significantly higher similarity in the gut microbial community than that of adult females in separate OMUs might be associated with the sexual differences in their interactions and from previously having cohabitated together in the AMU.Therefore,this study suggested that multilevel societies might have an effect on the gut microbial community in this wild nonhuman primate species.
