scholarly journals Changes in the gut microbiota and fermentation products associated with enhanced longevity in acarbose-treated mice

2018 ◽  
Author(s):  
Byron J Smith ◽  
Richard A Miller ◽  
Aaron C Ericsson ◽  
David C Harrison ◽  
Randy Strong ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Proportional Hazards ◽  
Short Chain Fatty Acids ◽  
Cox Proportional Hazards ◽  
Independent Study ◽  
Fermentation Products ◽  
Fecal Microbiome ◽  
Acarbose Treatment ◽  
Study Sites

AbstractBackgroundTreatment with theα-glucosidase inhibitor acarbose increases median lifespan by approximately 20% in male mice and 5% in females. This longevity extension differs from dietary restriction based on a number of features, including the relatively small effects on weight and the sex-specificity of the lifespan effect. By inhibiting host digestion, acarbose increases the flux of starch to the lower digestive system, resulting in changes to the gut microbiota and their fermentation products. Given the documented health benefits of short-chain fatty acids (SCFAs), the dominant products of starch fermentation by gut bacteria, this secondary effect of acarbose could contribute to increased longevity in mice. To explore this hypothesis, we compared the fecal microbiome of mice treated with acarbose to control mice at three independent study sites.ResultsMicrobial communities and the concentrations of SCFAs in the feces of mice treated with acarbose were notably different from those of control mice. At all three study sites, the bloom of a single bacterial taxon was the most obvious response to acarbose treatment. The blooming populations were classified to the largely unculturedBacteroidalesfamilyMuribaculaceaeand were the same taxonomic unit at two of the three sites. Total SCFA concentrations in feces were increased in treated mice, with increased butyrate and propionate in particular. Across all samples,Muribaculaceaeabundance was strongly correlated with propionate and community composition was an important predictor of SCFA concentrations. Cox proportional hazards regression showed that the fecal concentrations of acetate, butyrate, and propionate were, together, predictive of mouse longevity even while controlling for sex, site, and acarbose.ConclusionWe have demonstrated a correlation between fecal SCFAs and lifespan in mice, suggesting a role of the gut microbiota in the longevity-enhancing properties of acarbose. Treatment modulated the taxonomic composition and fermentation products of the gut microbiome, while the site-dependence of the microbiota illustrates the challenges facing reproducibility and interpretation in microbiome studies. These results motivate future studies exploring manipulation of the gut microbial community and its fermentation products for increased longevity, and to test a causal role of SCFAs in the observed effects of acarbose.

scholarly journals Muribaculaceae genomes assembled from metagenomes suggest genetic drivers of differential response to acarbose treatment in mice

2020 ◽  
Author(s):  
Byron J. Smith ◽  
Richard A. Miller ◽  
Thomas M. Schmidt
Keyword(s):  
Small Intestine ◽  
Short Chain Fatty Acids ◽  
Ecological Niches ◽  
Gut Health ◽  
Fermentation Products ◽  
Starch Fermentation ◽  
The Family ◽  
Acarbose Treatment ◽  
Genes Encoding ◽  
Study Sites

AbstractThe drug acarbose (ACA) is used to treat diabetes, and, by inhibiting α-amylase in the small intestine, increases the amount of starch entering the lower digestive tract. This results in changes to the composition of the microbiota and their fermentation products. Acarbose also increases longevity in mice, an effect that has been correlated with increased production of the short-chain fatty acids propionate and butyrate. In experiments replicated across three study sites, two distantly related species in the bacterial family Muribaculaceae were dramatically more abundant in ACA-treated mice, distinguishing these responders from other members of the family. Bacteria in the family Muribaculaceae are predicted to produce propionate as a fermentation end product and are abundant and diverse in the guts of mice, although few isolates are available. We reconstructed genomes from metagenomes (MAGs) for nine populations of Muribaculaceae to examine factors that distinguish species that respond positively to acarbose. We found two closely related MAGs (B1A and B1B) from one responsive species that both contain a polysaccharide utilization locus with a predicted extracellular α-amylase. These genomes also shared a periplasmic neopullulanase with another, distantly related MAG (B2) representative of the only other responsive species. This gene differentiated these three MAGs from MAGs representative of non-responding species. Differential gene content in B1A and B1B may be associated with the inconsistent response of this species to acarbose across study sites. This work demonstrates the utility of culture-free genomics for inferring the ecological roles of gut bacteria including their response to pharmaceutical perturbations.ImportanceThe drug acarbose is used to treat diabetes by preventing the breakdown of starch in the small intestine, resulting in dramatic changes in the abundance of some members of the gut microbiome and its fermentation products. In mice, several of the bacteria that respond most positively are classified in the family Muribaculaceae, members of which produce propionate as a primary fermentation product. Propionate has been associated with gut health and increased longevity in mice. We found that genomes of the most responsive Muribaculaceae showed signs of specialization for starch fermentation, presumably providing them a competitive advantage in the large intestine of animals consuming acarbose. Comparisons among genomes enhance existing models for the ecological niches occupied by members of this family. In addition, genes encoding one type of enzyme known to participate in starch breakdown were found in all three genomes from responding species, but none of the other genomes.

scholarly journals Therapeutic Role of Retroperitoneal Lymphadenectomy in 170 Patients With Ovarian Clear Cell Cancer

2022 ◽  
Vol 11 ◽  
Author(s):  
Wen Gao ◽  
Peipei Shi ◽  
Haiyan Sun ◽  
Meili Xi ◽  
Wenbin Tang ◽  
...  
Keyword(s):  
Tumor Recurrence ◽  
Proportional Hazards ◽  
Clear Cell ◽  
Cell Cancer ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Advanced Stage ◽  
Therapeutic Role ◽  
Retroperitoneal Lymphadenectomy

IntroductionWe evaluated the therapeutic role of retroperitoneal lymphadenectomy in patients with ovarian clear cell cancer (OCCC).Materials and MethodsWe retrospectively reviewed 170 OCCC patients diagnosed at two hospitals in China between April 2010 and August 2020. Clinical data were abstracted, and patients were followed until February 2021. Patients were divided into retroperitoneal lymphadenectomy and no lymphadenectomy groups. The Kaplan–Meier method was used to compare progression-free (PFS) and overall survival (OS) between the two groups. Statistical differences were determined by the log-rank test. The COX proportional hazards regression model was applied to identify predictors of tumor recurrence.ResultsThe median age was 52 years; 90 (52.9%) and 80 (47.1%) patients were diagnosed as early and advanced stage, respectively. Clinically positive and negative nodes was found in 40 (23.5%) and 119 (70.0%) patients, respectively. Of all the 170 patients, 124 (72.9%) patients underwent retroperitoneal lymphadenectomy, while 46 (27.1%) did not. The estimated 2-year PFS and 5-year OS rates were 71.4% and 65.9% in the lymphadenectomy group, and 72.0% and 73.7% in no lymphadenectomy group (p = 0.566 and 0.669, respectively). There was also no difference in survival between the two groups when subgroup analysis was performed stratified by early and advanced stage, or in patients with clinically negative nodes. Multivariate analysis showed that retroperitoneal lymphadenectomy were not an independent predictor of tumor recurrence.ConclusionRetroperitoneal lymphadenectomy provided no survival benefit in patients diagnosed with OCCC. A prospective clinical trial is needed to confirm the present results.

scholarly journals Reduced fecal short-chain fatty acids levels and the relationship with gut microbiota in IgA nephropathy

2021 ◽  
Author(s):  
Lingxiong Chai ◽  
Qun Luo ◽  
Kedan Cai ◽  
Kaiyue Wang ◽  
Binbin Xu
Keyword(s):  
Gut Microbiota ◽  
Iga Nephropathy ◽  
Butyric Acid ◽  
Intestinal Flora ◽  
Short Chain Fatty Acids ◽  
Caproic Acid ◽  
Isobutyric Acid ◽  
Control Group ◽  
Β Diversity

Abstract Background: IgA nephropathy(IgAN)) is the common pathological type of glomerular diseases. The role of gut microbiota in mediating "gut-IgA nephropathy" has not received sufficient attention in the previous studies. The purpose of this study was to investigate the changes of fecal short-chain fatty acids(SCFAs), a metabolite of the intestinal microbiota, in patients with IgAN and its correlation with intestinal flora and clinical indicators, and to further investigate the role of the gut-renal axis in IgAN.Methods: There were 29 patients with IgAN and 29 normal control subjects recruited from January 2018 to May 2018. The fresh feces were collected. The fecal SCFAs were measured by gas chromatography/mass spectrometry and gut microbiota was analysed by16S rDNA sequences, followed by estimation of α- and β-diversity. Correlation analysis was performed using the spearman’s correlation test between SCFAs and gut microbiota. Results:The levels of acetic acid, propionic acid, butyric acid, isobutyric acid and caproic acid in the IgAN patients were significantly reduced compared with control group(P<0.05). Butyric acid(r=-0.336, P=0.010) and isobutyric acid(r=-0.298, P=0.022) were negatively correlated with urea acid; butyric acid(r=-0.316, P=0.016) was negatively correlated with urea nitrogen; caproic acid(r=-0.415,P=0.025) showed negative correlation with 24-h urine protein level.Exemplified by the results of α-diversity and β-diversity, the intestinal flora of IgAN patients was significantly different from that of the control group. Acetic acid was positively associated with c_Clostridia(r=0.357, P=0.008), o_Clostridiales(r=0.357, P=0.008) and g_Eubacterium_coprostanoligenes_group(r=0.283, P=0.036). Butyric acid was positively associated with g_Alistipes (r=0.278, P=0.040). The relative abundance of those were significantly decreased in IgAN group compared to control group.Conclusion: The levels of fecal SCFAs in the IgAN patients were reduced, and correlated with clinical parameters and gut microbiota, which may be involved in the pathogenesis of IgAN, and this finding may provide a new therapeutic approach.

scholarly journals Supper Timing and Cardiovascular Mortality: The Japan Collaborative Cohort Study

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3389
Author(s):  
Jingyun Tang ◽  
Jia-Yi Dong ◽  
Ehab S. Eshak ◽  
Renzhe Cui ◽  
Kokoro Shirai ◽  
...  
Keyword(s):  
Hemorrhagic Stroke ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Stroke Mortality ◽  
Hazard Ratios ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
Study Participants

Evidence on the role of supper timing in the development of cardiovascular disease (CVD) is limited. In this study, we examined the associations between supper timing and risks of mortality from stroke, coronary heart disease (CHD), and total CVD. A total of 28,625 males and 43,213 females, aged 40 to 79 years, free from CVD and cancers at baseline were involved in this study. Participants were divided into three groups: the early supper group (before 8:00 p.m.), the irregular supper group (time irregular), and the late supper group (after 8:00 p.m.). Cox proportional hazards regression models were used to calculate hazard ratios (HRs) for stroke, CHD, and total CVD according to the supper time groups. During the 19-year follow-up, we identified 4706 deaths from total CVD. Compared with the early supper group, the multivariable HR of hemorrhagic stroke mortality for the irregular supper group was 1.44 (95% confidence interval [CI]: 1.05–1.97). There was no significant association between supper timing and the risk of mortality from other types of stroke, CHD, and CVD. We found that adopting an irregular supper timing compared with having dinner before 8:00 p.m. was associated with an increased risk of hemorrhagic stroke mortality.

scholarly journals Characteristics and consequences of medical care interruptions in HIV-infected patients in France

2016 ◽  
Vol 144 (11) ◽  
pp. 2363-2370 ◽  
Author(s):  
L. CUZIN ◽  
P. DELLAMONICA ◽  
Y. YAZDANPANAH ◽  
S. BOUCHEZ ◽  
D. REY ◽  
...  
Keyword(s):  
Medical Care ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Time Interval ◽  
Hiv Diagnosis ◽  
Viral Loads ◽  
Treatment Benefits ◽  
Cox Proportional Hazards Models ◽  
Sex With Men

SUMMARYTo describe the consequences of medical care interruptions (MCIs) we selected patients with at least two medical encounters between January 2006 and June 2013 in the Dat'AIDS cohort. Patients with any time interval >15 months between two visits were defined as having a MCI, as opposed to uninterrupted follow-up (UFU). Patients’ characteristics at the time of HIV diagnosis and at the censoring date were compared between groups. Cox proportional hazards models were built to assess the role of interruptions on survival (total and AIDS-free). Of 11 116 patients, 824 had at least one MCI. These patients were younger at the time of HIV diagnosis (30vs. 33 years,P< 0·0001). MCI was less frequent in men having sex with menvs.heterosexual patients [odds ratio (OR) 0·81, 95% confidence interval (CI) 0·69–0·96)], and a centre effect was described. MCI was independently associated with AIDS (OR 2·54, 95% CI 2·10–3·09) and death (OR 2·65, 95% CI 1·94–3·61). At the censoring date, 52·2% of patients with at least one MCI had viral load below detectionvs.85·3% of the UFU group (P< 0·0001). In conclusion, MCIs were associated with patients’ survival and with the proportion of viral loads below detection in our cohort, compromising individual and collective treatment benefits.

scholarly journals Rett Syndrome and Other Neurodevelopmental Disorders Share Common Changes in Gut Microbial Community: A Descriptive Review

2019 ◽  
Vol 20 (17) ◽  
pp. 4160 ◽  
Author(s):  
Elisa Borghi ◽  
Aglaia Vignoli
Keyword(s):  
Microbial Community ◽  
Gut Microbiota ◽  
Rett Syndrome ◽  
Neurodevelopmental Disorders ◽  
Short Chain Fatty Acids ◽  
Dynamic Effects ◽  
Common Pathway ◽  
Gut Microbial Community ◽  
Host Metabolism

In this narrative review, we summarize recent pieces of evidence of the role of microbiota alterations in Rett syndrome (RTT). Neurological problems are prominent features of the syndrome, but the pathogenic mechanisms modulating its severity are still poorly understood. Gut microbiota was recently demonstrated to be altered both in animal models and humans with different neurodevelopmental disorders and/or epilepsy. By investigating gut microbiota in RTT cohorts, a less rich microbial community was identified which was associated with alterations of fecal microbial short-chain fatty acids. These changes were positively correlated with severe clinical outcomes. Indeed, microbial metabolites can play a crucial role both locally and systemically, having dynamic effects on host metabolism and gene expression in many organs. Similar alterations were found in patients with autism and down syndrome as well, suggesting a potential common pathway of gut microbiota involvement in neurodevelopmental disorders.

scholarly journals MECHANISMS IN ENDOCRINOLOGY: Gut microbiota in patients with type 2 diabetes mellitus

2015 ◽  
Vol 172 (4) ◽  
pp. R167-R177 ◽  
Author(s):  
Kristine H Allin ◽  
Trine Nielsen ◽  
Oluf Pedersen
Keyword(s):  
Type 2 Diabetes ◽  
Gut Microbiota ◽  
Metabolic Diseases ◽  
Short Chain Fatty Acids ◽  
Intestinal Content ◽  
Low Grade ◽  
Bacterial Fermentation ◽  
Underlying Mechanisms

Perturbations of the composition and function of the gut microbiota have been associated with metabolic disorders including obesity, insulin resistance and type 2 diabetes. Studies on mice have demonstrated several underlying mechanisms including host signalling through bacterial lipopolysaccharides derived from the outer membranes of Gram-negative bacteria, bacterial fermentation of dietary fibres to short-chain fatty acids and bacterial modulation of bile acids. On top of this, an increased permeability of the intestinal epithelium may lead to increased absorption of macromolecules from the intestinal content resulting in systemic immune responses, low-grade inflammation and altered signalling pathways influencing lipid and glucose metabolism. While mechanistic studies on mice collectively support a causal role of the gut microbiota in metabolic diseases, the majority of studies in humans are correlative of nature and thus hinder causal inferences. Importantly, several factors known to influence the risk of type 2 diabetes, e.g. diet and age, have also been linked to alterations in the gut microbiota complicating the interpretation of correlative studies. However, based upon the available evidence, it is hypothesised that the gut microbiota may mediate or modulate the influence of lifestyle factors triggering development of type 2 diabetes. Thus, the aim of this review is to critically discuss the potential role of the gut microbiota in the pathophysiology and pathogenesis of type 2 diabetes.

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