Gut microbiota patterns associated with somatostatin in patients undergoing pancreaticoduodenectomy: a prospective study.
ABSTRACT: Postoperative pancreatic fistula (POPF) is a common and dreaded complication after pancreaticoduodenectomy (PD). The gut microbiota has been considered as an crucial mediator of postoperative complications, however, the precise roles of gut microbiota in POPF are unclear. A prospective study was developed to explore the effects of somatostatin on gut microbiota and we aim to identify the microbial alterations in the process of POPF. A total of 45 patients were randomly divided into PD group or additional somatostatin therapy group. The fecal sample of each patient was collected preoperatively and postoperatively and the gut microbiota was analyzed by 16S rRNA sequencing. Our study found that somatostatin therapy was independent risk factor for the occurrence of POPF, and it reduced the microbial diversity and richness in patients. At genus level, somatostatin therapy led to a decreased abundance in Bifidobacterium, Subdoligranulum and Dubosiella, whereas the abundance of Akkermansia, Enterococcus and Enterobacter were increased. The abundance levels of certain bacteria in the gut microbiota have significantly shifted in patients with POPF. The LEfSe analysis revealed that Ruminococcaceae could be used as microbial markers for distinguishing patients with high risk of POPF. Furthermore, Verrucomicrobia and Akkermansia could be used as preoperative biomarkers for identifying patients without POPF. Our prospective study highlights the specific communities related with somatostatin therapy and discovers POPF-associated microbial marker, which suggests that gut microbiota may become a diagnostic biomarker and potential therapeutic target for POPF.
Project description:We aimed to investigate the association of gut microbiota with disease activity, inflammatory parameters, and auto-antibodies profile in rheumatoid arthritis (RA). A total of 138 RA patients and 21 healthy controls (HC) were enrolled. Fecal samples were collected for bacterial DNA extraction and 16S ribosome (r)RNA sequencing, followed by analyses of gut microbiota composition. Serum levels of tumor necrosis factor (TNF)-?, interleukin (IL)-6, and IL-17A were determined by using ELISA. Our results indicated that RA patients had lower diversity index, which reflects both evenness and richness of gut microbiota, compared to HC. The alpha-diversity was lower in anti-citrullinated peptide antibodies (ACPA)-positive patients than in HC. The phylum Verrucomicrobiae and genus Akkermansia were more abundant in patients compared to HC. There was increased relative abundance of Enterobacteriaceae as well as Klebsiella, and less abundance of Bifidobacterium in patients with high levels of TNF-? or IL-17A compared to those who had low levels of these cytokines. In addition, ACPA-positive patients had higher proportions of Blautia, Akkermansia, and Clostridiales than ACPA-negative patients. Gut dysbiosis in RA patients was presented as different microbial composition and its association with inflammatory parameters as well as ACPA seropositivity. These findings support the involvement of gut microbiota in RA pathogenesis.
Project description:BACKGROUND:The gut microbiota is associated with diverse age-related disorders. Several rejuvenation methods, such as probiotic administration and faecal microbiota transplantation, have been applied to alter the gut microbiome and promote healthy ageing. Nevertheless, prolongation of the health span of aged mice by remodelling the gut microbiome remains challenging. RESULTS:Here, we report the changes in gut microbial communities and their functions in mouse models during ageing and three rejuvenation procedures including co-housing, serum-injection and parabiosis. Our results showed that the compositional structure and gene abundance of the intestinal microbiota changed dynamically during the ageing process. Through the three rejuvenation procedures, we observed that the microbial community and intestinal immunity of aged mice were comparable to those of young mice. The results of metagenomic data analysis underscore the importance of the high abundance of Akkermansia and the butyrate biosynthesis pathway in the rejuvenated mouse group. Furthermore, oral administration of Akkermansia sufficiently ameliorated the senescence-related phenotype in the intestinal systems in aged mice and extended the health span, as evidenced by the frailty index and restoration of muscle atrophy. CONCLUSIONS:In conclusion, the changes in key microbial communities and their functions during ageing and three rejuvenation procedures, and the increase in the healthy lifespan of aged mice by oral administration of Akkermansia. Our results provide a rationale for developing therapeutic strategies to achieve healthy active ageing. Video abstract.
Project description:<h4>Objective</h4><i>Akkermansia muciniphila</i> is among the most abundant bacterial species in the human intestine; however, its relationship to metabolic syndrome (MetS)-which is linked to gut dysbiosis-is not known. In this study, we investigated the association between <i>Akkermansia</i> abundance and risk of MetS and its components, as well as dose-response effects and the influence of microbial interactions on the association.<h4>Methods</h4>This cross-sectional study included 6896 Chinese participants aged 18 to 97 years from the Guangdong Gut Microbiome Project. MetS was defined according to Joint Committee for Developing Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults criteria. The abundance of <i>Akkermansia</i> was assessed by 16S rRNA sequencing. Logistic regression analysis with adjustment for common confounders was performed to evaluate the association between <i>Akkermansia</i> and MetS and its components. Models with restricted cubic splines and interaction terms were used to examine the dose-response association and microbial interactions, respectively.<h4>Results</h4>The prevalence of MetS was 20.4%, and the median abundance of <i>Akkermansia</i> was 0.08% (interquartile range: 0.04-0.93%). Increased <i>Akkermansia</i> abundance was associated with decreased risk of MetS (<i>P</i> <sub>nonlinear</sub><0.05), but this effect was not observed until the <i>Akkermansia</i> level was 0.2% of the total gut microbiota abundance (odds ratio=0.96, 95% confidence interval: 0.94-0.98). Of the 5 MetS components, obesity and hypertriglyceridemia showed the strongest association with <i>Akkermansia</i>, followed by reduced high-density lipoprotein cholesterol, hypertension, and hyperglycemia. Microbial interaction analyses showed that Ruminococcaceae and Lachnospiraceae were the predominant bacterial families and were not only correlated with <i>Akkermansia</i> abundance but also influenced the <i>Akkermansia</i>-MetS association.<h4>Conclusion</h4>There is a dose-response association between reduced risk of MetS and increased abundance of <i>Akkermansia</i>. The association between <i>Akkermansia</i> and 5 MetS components is variable and affected by microbial interactions.
Project description:<h4>Background</h4>Flavonoids are reported to modulate the composition of gut microbiota, which play an important role in preventing obesity and associated metabolic diseases. In this study, we investigated the effect of Total Flavonoids of Quzhou Fructus Aurantii Extract (TFQ) on gut microbial community in mice fed with a high-fat diet (HFD).<h4>Methods</h4>C57BL/6J mice were fed with either a chow diet or HFD with or without oral gavage of TFQ (300?mg/kg/day) for 12 weeks.<h4>Results</h4>Our data indicate TFQ significantly reduced obesity, inflammatio,n and liver steatosis. TFQ elevates the expression of tight junction proteins and reduces metabolic endotoxemia. In addition, TFQ treatment reverses HFD-induced gut dysbiosis, as indicated by the reduction of Firmicutes to Bacteroidetes ratio, the increase of genera Akkermansia and Alistipes, and the decrease of genera Dubosiella, Faecalibaculum, and Lactobacillus.<h4>Conclusion</h4>These findings support a prebiotic role of TFQ as a dietary supplement for the intervention of gut dysbiosis and obesity-related metabolic disorders.
Project description:Recent evidence indicates that the gut microbiota plays a key role in the pathophysiology of obesity. Indeed, diet-induced obesity (DIO) has been associated to substantial changes in gut microbiota composition in rodent models. In the context of obesity, enhanced adiposity is accompanied by low-grade inflammation of this tissue but the exact link with gut microbial community remains unknown. In this report, we studied the consequences of high-fat diet (HFD) administration on metabolic parameters and gut microbiota composition over different periods of time. We found that Akkermansia muciniphila abundance was strongly and negatively affected by age and HFD feeding and to a lower extend Bilophila wadsworthia was the only taxa following an opposite trend. Different approaches, including multifactorial analysis, showed that these changes in Akkermansia muciniphila were robustly correlated with the expression of lipid metabolism and inflammation markers in adipose tissue, as well as several circulating parameters (i.e., glucose, insulin, triglycerides, leptin) from DIO mice. Thus, our data shows the existence of a link between gut Akkermansia muciniphila abundance and adipose tissue homeostasis on the onset of obesity, thus reinforcing the beneficial role of this bacterium on metabolism.
Project description:Caffeic acid (CA) is one of the major phenolic acids of coffee with multiple biological activities. Our previous study found that 500 mg/kg of chlorogenic acid (CGA) had the potential capacity of alleviating colonic inflammation. Moreover, CGA can be degraded into caffeic acid (CA) by the gut microbiota in the colon. Therefore, we hypothesize that CA can exert protective effects on colonic inflammation. To test the hypothesis, 251 mg/kg CA was supplemented to DSS-induced colitis mice. The results showed that CA treatment recovered DSS-induced disease activity index (DAI), colon length, and histopathology scores of colon tissue. Additionally, CA treatment significantly decreased pro-inflammatory cytokines and malondialdehyde (MDA) levels and increased the level of IL-10, total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in serum. qPCR results indicated that CA treatment dramatically downregulated mRNA expression of <i>IL-1β</i>, <i>IL-6</i>, and <i>TNF-α</i> as well as upregulated <i>SOD1</i>, <i>GPX1</i>, <i>GPX2</i>, <i>CAT</i>, and <i>IL-10</i>. In addition, CA supplementation significantly increased mRNA expression of <i>Nrf-2</i>, <i>HO-1</i>, and <i>NQO1</i>, which showed its antioxidant and anti-inflammatory capacities potentially by activating the Nrf-2/HO-1 pathway. Moreover, CA supplementation prevented gut barrier damage by enhancing <i>Occludin</i> gene expression. Furthermore, CA supplementation altered the gut microbiome composition by decreasing the relative abundance of <i>Bacteroides</i> and <i>Turicibacter</i>, and enhancing the relative abundance of <i>Alistipes</i> and <i>Dubosiella</i>. Meanwhile, CA supplementation increases the abundance of <i>Dubosiella</i> and <i>Akkermansia</i>. In conclusion, CA supplementation could effectively alleviate DSS-induced colitis by improving the defense against oxidative stress and inflammatory response.
Project description:<h4>Background</h4>Coffee can regulate glucose homeostasis but the underlying mechanism is unclear. This study investigated the preventive and therapeutic effects of chlorogenic acid (CGA), a polyphenol that is found in coffee, on obesity and obesity-related metabolic endotoxemia.<h4>Method</h4>Male 4-week-old C57BL/6 mice were fed either normal chow or a high-fat diet or 20 weeks and half the mice in each group were gavaged with CGA. Oral glucose tolerance tests (OGTTs) and insulin tolerance tests (ITTs) were performed. Markers of inflammation and intestinal barrier function were assayed. The composition of the gut microbiota was analyzed by 16S rRNA high-throughput pyrosequencing. The role of CGA-altered microbiota in metabolic endotoxemia was verified by fecal microbiota transplantation.<h4>Results</h4>CGA protected against HFD-induced weight gain, decreased the relative weight of subcutaneous and visceral adipose, improved intestinal barrier integrity, and prevented glucose metabolic disorders and endotoxemia (<i>P <</i>0.05). CGA significantly changed the composition of the gut microbiota and increased the abundance of short chain fatty acid (SCFA)-producers (e.g., <i>Dubosiella</i>, <i>Romboutsia</i>, <i>Mucispirillum</i>, and <i>Faecalibaculum</i>) and <i>Akkermansia</i>, which can protect the intestinal barrier. In addition, mice with the CGA-altered microbiota had decreased body weight and fat content and inhibited metabolic endotoxemia.<h4>Conclusion</h4>CGA-induced changes in the gut microbiota played an important role in the inhibition of metabolic endotoxemia in HFD-fed mice.
Project description:Berries are rich in polyphenols and plant cell wall polysaccharides (fibers), including cellulose, hemicellulose, arabinans and arabino-xyloglucans rich pectin. Most of polyphenols and fibers are known to be poorly absorbed in the small intestine and reach the colon where they interact with the gut microbiota, conferring health benefits to the host. This study assessed the contribution of polyphenol-rich whole cranberry and blueberry fruit powders (CP and BP), and that of their fibrous fractions (CF and BF) on modulating the gut microbiota, the microbial functional profile and influencing metabolic disorders induced by high-fat high-sucrose (HFHS) diet for 8 weeks. Lean mice-associated taxa, including Akkermansia muciniphila, Dubosiella newyorkensis, and Angelakisella, were selectively induced by diet supplementation with polyphenol-rich CP and BP. Fiber-rich CF also triggered polyphenols-degrading families Coriobacteriaceae and Eggerthellaceae. Diet supplementation with polyphenol-rich CP, but not with its fiber-rich CF, reduced fat mass depots, body weight and energy efficiency in HFHS-fed mice. However, CF reduced liver triglycerides in HFHS-fed mice. Importantly, polyphenol-rich CP-diet normalized microbial functions to a level comparable to that of Chow-fed controls. Using multivariate association modeling, taxa and predicted functions distinguishing an obese phenotype from healthy controls and berry-treated mice were identified. The enterotype-like clustering analysis underlined the link between a long-term diet intake and the functional stratification of the gut microbiota. The supplementation of a HFHS-diet with polyphenol-rich CP drove mice gut microbiota from Firmicutes/Ruminococcus enterotype into an enterotype linked to healthier host status, which is Prevotella/Akkermansiaceae. This study highlights the prebiotic role of polyphenols, and their contribution to the compositional and functional modulation of the gut microbiota, counteracting obesity.
Project description:<b>Background</b>: There is accumulating evidence suggesting a connection between the gut and Parkinson's disease (PD). Gut microbiota may play an important role in the intestinal lesions in PD patients. <b>Objective</b>: This study aims to determine whether gut microbiota differs between PD patients and healthy controls in Northeast of China, and to identify the factors that influence the changes in the gut microbiota. <b>Methods</b>: We enrolled 51 PD patients and 48 healthy controls in this study. Microbial species in stool samples were determined through 16S-rRNA gene sequencing. Dietary intakes were collected from a subset of 42 patients and 23 controls using a food frequency questionnaire (FFQ). Gut microbiota species richness, diversity, differential abundance of individual taxa between PD patients and controls, and the relationship between the gut microbiota abundance and the dietary and clinical factors were analyzed. <b>Results</b>: PD patients showed decreased species richness, phylogenetic diversity, ?- diversity, and altered relative abundance in several taxa compared to the controls. PD- associated clinical scores appeared to be the most influential factors that correlated with the abundance of a variety of taxa. The most consistent findings suggested by multiple analyses used in this study were the increase of <i>Akkermansia</i> and the decrease of <i>Lactobacillus</i> in PD patients in Northeast China. <b>Conclusion</b>: Gut microbiota significantly differed between a group of PD patients and healthy controls in Northeast China, with decreased species richness, phylogenetic diversity, ?-diversity, and altered relative abundance in several taxa compared to the controls.
Project description:Microbiota alterations have been recently investigated in individuals with epilepsy and in other neurological diseases as environmental factors that play a role, by acting through the gut-brain axis, in the pathological process. Most studies focus on the contribution of bacterial communities in refractory epilepsy and suggest a beneficial role of ketogenic diet in modulating the gut microbiota and seizure occurrence. However, they do not evaluate whether epilepsy itself alters the gut microbiota in these patients or if the gut microbial communities could contribute as a seizure trigger. In this pilot study, we performed 16S rRNA sequencing and investigated the gut microbial communities of eight children at their seizure onset and after anti-seizure was started (one year follow-up) and we compared microbial data with seven healthy children, age- and sex-matched. In drug-naive subjects, we observed a microbial signature that shared several features with those reported in refractory epilepsy, such as an increased abundance in <i>Akkermansia</i> spp. and Proteobacteria and a decreased relative abundance in <i>Faecalibacterium</i> spp.We suggest that a bacterial-mediated proinflammatory milieu could contribute to seizure occurrence in children with new onset of epilepsy, as already reported for individuals with drug-resistant epilepsy, and that it could vary during treatment in those who are drug-responsive.