Effects of acupuncture on gut microbiota and short-chain fatty acids in patients with functional constipation: a randomized placebo-controlled trial
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ABSTRACT:
SUBMITTER: Yan X
PROVIDER: S-EPMC10502303 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:Many studies have focused on the metabolic capacity of human gut microbiota to produce short-chain fatty acids and subsequent effects on host physiology. Given scarce data on how SCFAs produced by gut bacteria participate in cross-feeding to influence community structure and function, we evaluated the potential of SCFAs to modulate human gut microbiota in vitro. We employed anaerobic fecal cultivation in chemically defined medium supplemented with one of nine SCFAs to determine effects on both gut microbial community structure via 16S rRNA sequencing and function via genome reconstruction analysis. Each SCFA displayed significant and unique modulatory potential with respect to the relative abundance of bacterial taxa. Analysis of SCFA-supplemented communities revealed that alterations of individual closely related phylotypes displayed coherent changes, although exceptions were also observed which suggest strain-dependent differences in SCFA-induced changes. We used genome reconstruction to evaluate the functional implications of SCFA-mediated restructuring of fecal communities. We note that some SCFA-supplemented cultures displayed a reduction in the predicted abundance of SCFA producers, which suggests a possible undefined negative feedback mechanism. We conclude that SCFAs are not simply end-products of metabolism but also serve to modulate the gut microbiota through cross-feeding that alters the fitness of specified taxa. These results are important in the identification of prebiotics that elevate specific SCFAs for therapeutic benefit and highlight SCFA consumers as a salient part of the overall metabolic flux pertaining to bacterial fermentative processes.
| S-EPMC8921067 | biostudies-literature
Project description:In recent years, short-chain fatty acids (SCFAs) have been reported to play an important role in maintaining human health. Fecal SCFA concentrations correlate well with colonic SCFA status and gut microbiota composition. However, the associations with the gut microbiota functional pathway, dietary intake, blood SCFAs, and fecal SCFAs remain uncertain. To clarify these relationships, we collected fecal samples, blood samples, and dietary habit data from 12 healthy adults aged 22-51 years. The relative abundance of several SCFA-producing bacteria, gut microbiota diversity, and functional pathways related to SCFA biosynthesis were positively associated with fecal SCFAs even after adjusting for age and sex. Furthermore, fecal acetate was likely to be positively associated with serum acetate. By contrast, dietary intake was not associated with fecal SCFAs. Overall, the present study highlights the potential usefulness of fecal SCFAs as an indicator of the gut microbiota ecosystem and dynamics of SCFAs in the human body.
| S-EPMC6971417 | biostudies-literature
Project description:The goal of this study is to compare transcriptome profiling of n-butyrate treated immortalized human endometriotic epithelial cells expression Luciferase (iHEECs/Luc) by RNA-sequencing Methods: The mRNA profiles of vehicle and n-butyrate treated immortalized human endometriotic epithelial cells expression Luciferase (iHEECs/Luc) were generated by deep sequencing, in triplicate using Illumina NovaSeq-6000 sequencers with 2×150 paired-end reads. Basecalls and demultiplexing were performed with Illumina’s RTA version 1.9 and bcl2fastq2 software with a maximum of one mismatch in the indexing read. RNA-seq reads were then aligned to the Ensembl release 76 primary assembly with STAR version 2.5.1a. qRT–PCR validation was performed using TaqMan assays. Results: Using a 2.5-fold cutoff and Benjamini-Hochberg false discovery rate (FDR) of <0.01 threshold for inclusion, we identified 1,830 differentially expressed genes (DEGs) between Vehicle and n-butyrate treated immortalized human endometriotic epithelial cells expression Luciferase (iHEECs/Luc). Conclusions: Our study represents the first detailed analysis of n-butyrate treated immortalized human endometriotic epithelial cells expression Luciferase (iHEECs/Luc) transcriptomes, with biologic replicates, generated by RNA-seq technology.
2021-09-29 | GSE184431 | GEO
Project description:A growing body of evidence highlights the relevance of free fatty acids (FFA) for human health, and their role in the cross talk between the metabolic status and immune system. Altered serum FFA profiles are related to several metabolic conditions, although the underlying mechanisms remain unclear. Recent studies have highlighted the link between gut microbiota and host metabolism. However, although most of the studies have focused on different clinical conditions, evidence on the role of these mediators in healthy populations is lacking. Therefore, we have addressed the analysis of the relationship among gut microbial populations, short-chain fatty acid (SCFA) production, FFA levels, and immune mediators (IFNγ, IL-6, and MCP-1) in 101 human adults from the general Spanish population. Levels of selected microbial groups, representing the major phylogenetic types present in the human intestinal microbiota, were determined by quantitative PCR. Our results showed that the intestinal abundance of Akkermansia was the main predictor of total FFA serum levels, displaying a negative association with total FFA and the pro-inflammatory cytokine IL-6. Similarly, an altered FFA profile, identified by cluster analysis, was related to imbalanced levels of Akkermansia and Lactobacillus as well as increased fecal SCFA, enhanced IL-6 serum levels, and higher prevalence of subclinical metabolic alterations. Although no differences in nutritional intakes were observed, divergent patterns in the associations between nutrient intakes with intestinal microbial populations and SCFA were denoted. Overall, these findings provide new insights on the gut microbiota-host lipid metabolism axis and its potential relevance for human health, where FFA and SCFA seem to play an important role.
| S-EPMC5522850 | biostudies-other
Project description:Worldwide, ∼196 million are afflicted with endometriosis, a painful disease in which endometrial tissue implants and proliferates on abdominal peritoneal surfaces. Theories on the origin of endometriosis remained inconclusive. Whereas up to 90% of women experience retrograde menstruation, only 10% develop endometriosis, suggesting that factors that alter peritoneal environment might contribute to endometriosis. Herein, we report that whereas some gut bacteria promote endometriosis, others protect against endometriosis by fermenting fiber to produce short-chain fatty acids. Specifically, we found that altered gut microbiota drives endometriotic lesion growth and feces from mice with endometriosis contained less of short-chain fatty acid and n-butyrate than feces from mice without endometriosis. Treatment with n-butyrate reduced growth of both mouse endometriotic lesions and human endometriotic lesions in a pre-clinical mouse model. Mechanistic studies revealed that n-butyrate inhibited human endometriotic cell survival and lesion growth through G-protein-coupled receptors, histone deacetylases, and a GTPase activating protein, RAP1GAP. Our findings will enable future studies aimed at developing diagnostic tests, gut bacteria metabolites and treatment strategies, dietary supplements, n-butyrate analogs, or probiotics for endometriosis.
| S-EPMC8500332 | biostudies-literature
Project description:The gut microbiome and its metabolites may be important role in regulating the pathogenesis of obesity. This study aimed to characterize the gut microbiome and short-chain fatty acid (SCFA) metabolome in obese children. This case-control study recruited children aged 7‒14 years and divided them into a normal group (NG) and an obese group (OG) based on their body mass index. Whole-genome shotgun metagenomic analysis was performed on fecal samples from the OG and NG groups to characterize the signatures and functional potential of the gut microbiota. Serum metabolite profiles were analyzed using high-performance liquid chromatography/mass spectrometry (LC/MS). The Statistical Package for the Social Sciences (SPSS, version 26) and R software were used for data analysis. A total of 99 children were recruited, with 49 in the OG and 50 in the NG. At the phylum level, Proteobacteria were significantly more abundant in children in the OG than those in the NG. At the genus level, Oscillibacter and Alistipes were significantly lower in children in the OG than those in the NG. Caproate levels significantly increased, whereas butyrate and isobutyrate levels decreased in children in the OG than those in the NG. Kyoto encyclopedia of genes and genomes (KEGG) functional analysis revealed 28 enriched KEGG pathways, of which/with the phosphotransferase system (PTS) and enhanced biofilm formation by Escherichia coli were particularly significant in the OG. Spearman's correlation analysis indicated that the genus Oscillibacter and species Clostridium_sp._CAG:302 connect serum metabolites and the gut microbiota in childhood obesity. Childhood obesity is correlated with the symbiotic status of the gut microbiota. The microbiota influences human metabolism via specific pathways, particularly butyrate, caproate, and the genus Oscillibacter, all closely associated with obesity.
| S-EPMC11695941 | biostudies-literature
Project description:RationaleThe elderly experience profound systemic responses after stroke, which contribute to higher mortality and more severe long-term disability. Recent studies have revealed that stroke outcomes can be influenced by the composition of gut microbiome. However, the potential benefits of manipulating the gut microbiome after injury is unknown.ObjectiveTo determine if restoring youthful gut microbiota after stroke aids in recovery in aged subjects, we altered the gut microbiome through young fecal transplant gavage in aged mice after experimental stroke. Further, the effect of direct enrichment of selective bacteria producing short-chain fatty acids (SCFAs) was tested as a more targeted and refined microbiome therapy.Methods and resultsAged male mice (18-20 months) were subjected to ischemic stroke by middle cerebral artery occlusion. We performed fecal transplant gavage 3 days after middle cerebral artery occlusion using young donor biome (2-3 months) or aged biome (18-20 months). At day 14 after stroke, aged stroke mice receiving young fecal transplant gavage had less behavioral impairment, and reduced brain and gut inflammation. Based on data from microbial sequencing and metabolomics analysis demonstrating that young fecal transplants contained much higher SCFA levels and related bacterial strains, we selected 4 SCFA-producers (Bifidobacterium longum, Clostridium symbiosum, Faecalibacterium prausnitzii, and Lactobacillus fermentum) for transplantation. These SCFA-producers alleviated poststroke neurological deficits and inflammation, and elevated gut, brain and plasma SCFA concentrations in aged stroke mice.ConclusionsThis is the first study suggesting that the poor stroke recovery in aged mice can be reversed via poststroke bacteriotherapy following the replenishment of youthful gut microbiome via modulation of immunologic, microbial, and metabolomic profiles in the host.
| S-EPMC7415518 | biostudies-literature
Project description:BackgroundPrevious studies have reported that gut microbiota, permeability, short-chain fatty acids (SCFAs), and inflammation are altered in Parkinson's disease (PD), but how these factors are linked and how they contribute to disease processes and symptoms remains uncertain. This study sought to compare and identify associations among these factors in PD patients and controls to elucidate their interrelations and links to clinical manifestations of PD.MethodsStool and plasma samples and clinical data were collected from 55 PD patients and 56 controls. Levels of stool SCFAs and stool and plasma inflammatory and permeability markers were compared between patients and controls and related to one another and to the gut microbiota.ResultsCalprotectin was increased and SCFAs decreased in stool in PD in a sex-dependent manner. Inflammatory markers in plasma and stool were neither intercorrelated nor strongly associated with SCFA levels. Age at PD onset was positively correlated with SCFAs and negatively correlated with CXCL8 and IL-1β in stool. Fecal zonulin correlated positively with fecal NGAL and negatively with PD motor and non-motor symptoms. Microbiota diversity and composition were linked to levels of SCFAs, inflammatory factors, and zonulin in stool. Certain relationships differed between patients and controls and by sex.ConclusionsIntestinal inflammatory responses and reductions in fecal SCFAs occur in PD, are related to the microbiota and to disease onset, and are not reflected in plasma inflammatory profiles. Some of these relationships are distinct in PD and are sex-dependent. This study revealed potential alterations in microbiota-host interactions and links between earlier PD onset and intestinal inflammatory responses and reduced SCFA levels, highlighting candidate molecules and pathways which may contribute to PD pathogenesis and clinical presentation and which warrant further investigation.
| S-EPMC7869249 | biostudies-literature
Project description:Postural orthostatic tachycardia syndrome (POTS) is a devastating chronic form of orthostatic intolerance associated with excessive heart rate increase without hypotension during upright posture. POTS patients exhibit increased circulating norepinephrine levels with exaggerated sympathetic nervous system response upon standing. Emerging evidence suggests a role for the gut microbiome in cardiovascular disorders. However, the etiology of POTS and whether the gut microbiome plays a role are not fully elucidated. We assessed whether the gut microbiome and fecal short-chain fatty acids were different in POTS patients (N = 25) compared to healthy control (N = 23) women. Patients underwent hemodynamic measurements while supine and upon standing. Fecal samples were collected and analyzed using shotgun sequencing and Liquid Chromatography-High Resolution Mass Spectrometry and dietary habits were measured with a fitness application. We found that POTS patients in the standing position had higher circulating norepinephrine and epinephrine levels and increased heart rate. There were no differences in diet composition between groups. Of note dietary salt intake was also similar despite the fact that these patients are advised to consume a high salt diet. Alpha and beta diversity were similar between groups. We observed no differences in bacteria at the phylum levels or Firmicutes to Bacteroidetes ratio. We found no significant differences at the genus level, but observed trends in certain bacteria. Lachnoclostridium genus were higher in POTS when compared to the control group. On the other hand, Coprococcus and Coprobacter, were lower in POTS patients compared to controls. Although our KEGG metabolic pathways indicated differences related to short-chain fatty acids (SCFAs), we found that both POTS patients and healthy controls had similar levels of SCFAs. These results suggest POTs per se may have limited effects on gut microbiota composition and derived SCFAs. Further studies are needed to assess the role of the alterations observed at the genus level.
| S-EPMC9208699 | biostudies-literature
Project description:BackgroundPrevious studies found the dysbiosis of intestinal microbiota in diabetic kidney disease (DKD), especially the decreased SCFA-producing bacteria. We aimed to investigate the concentration of the stool and serum short-chain fatty acids (SCFAs), gut microbiota-derived metabolites, in individuals with DKD and reveal the correlations between SCFAs and renal function.MethodsA total of 30 participants with DKD, 30 participants with type 2 diabetes mellitus (DM), and 30 normal controls (NC) in HwaMei Hospital were recruited from 1/1/2018 to 12/31/2019. Participants with DKD were divided into low estimated glomerular filtration rate (eGFR)(eGFR<60ml/min, n=14) and high eGFR (eGFR≥60ml/min, n=16) subgroups. Stool and serum were measured for SCFAs with gas chromatograph-mass spectrometry.ResultsThe DKD group showed markedly lower levels of fecal acetate, propionate, and butyrate versus NC (p<0.001, p<0.001, p=0.018, respectively) [1027.32(784.21-1357.90)]vs[2064.59(1561.82-2637.44)]μg/g,[929.53(493.65-1344.26)]vs[1684.57(1110.54-2324.69)]μg/g,[851.39(409.57-1611.65)] vs[1440.74(1004.15-2594.73)]μg/g, respectively, and the lowest fecal total SCFAs concentration among the groups. DKD group also had a lower serum caproate concentration than that with diabetes (p=0.020)[0.57(0.47-0.61)]vs[0.65(0.53-0.79)]μmol/L. In the univariate regression analysis, fecal and serum acetate correlated with eGFR (OR=1.013, p=0.072; OR=1.017, p=0.032). The correlation between serum total SCFAs and eGFR showed statistical significance (OR=1.019, p=0.024) unadjusted and a borderline significance (OR=1.024, p=0.063) when adjusted for Hb and LDL. The decrease in serum acetate and total SCFAs were found of borderline significant difference in both subgroups (p=0.055, p=0.050).ConclusionThis study provides evidence that in individuals with DKD, serum and fecal SCFAs levels (fecal level in particular) were lowered, and there was a negative correlation between SCFAs and renal function.
| S-EPMC8649351 | biostudies-literature