scholarly journals A short chain fatty acid–centric view of Clostridioides difficile pathogenesis

2021 ◽  
Vol 17 (10) ◽  
pp. e1009959
Author(s):  
Anna L. Gregory ◽  
Daniel A. Pensinger ◽  
Andrew J. Hryckowian
Keyword(s):  
Gut Microbiome ◽  
Molecular Mechanisms ◽  
Short Chain Fatty Acid ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Fecal Transplant ◽  
Clostridioides Difficile ◽  
Major Class ◽  
Future Work ◽  
Primary Risk Factor

Clostridioides difficile is an opportunistic diarrheal pathogen responsible for significant morbidity and mortality worldwide. A disrupted (dysbiotic) gut microbiome, commonly engendered by antibiotic treatment, is the primary risk factor for C. difficile infection, highlighting that C. difficile–microbiome interactions are critical for determining the fitness of this pathogen. Here, we review short chain fatty acids (SCFAs): a major class of metabolites present in the gut, their production by the gut microbiome, and their impacts on the biology of the host and of C. difficile. We use these observations to illustrate a conceptual model whereby C. difficile senses and responds to SCFAs as a marker of a healthy gut and tunes its virulence accordingly in order to maintain dysbiosis. Future work to learn the molecular mechanisms and genetic circuitry underlying the relationships between C. difficile and SCFAs will help to identify precision approaches, distinct from antibiotics and fecal transplant, for mitigating disease caused by C. difficile and will inform similar investigations into other gastrointestinal pathogens.

scholarly journals Fecal Short-Chain Fatty Acid Concentrations Increase in Newly Paired Male Marmosets (Callithrix jacchus)

mSphere ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Lifeng Zhu ◽  
Mallory J. Suhr Van Haute ◽  
Haley R. Hassenstab ◽  
Caroline Smith ◽  
Devin J. Rose ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Gut Microbiome ◽  
Short Chain Fatty Acid ◽  
Social Contact ◽  
Common Marmoset ◽  
Short Chain Fatty Acids ◽  
Chain Fatty Acid ◽  
Short Chain ◽  
Chain Fatty Acids

ABSTRACT The role by which the gut microbiome influences host health (e.g., energy equilibrium and immune system) may be partly mediated by short-chain fatty acids, which are bacterial fermentation products from the dietary fibers. However, little is known about longitudinal changes in gut microbiome metabolites during cohabitation alongside social contact. In common marmosets (Callithrix jacchus), the gut microbiome community is influenced by social contact, as newly paired males and females develop convergent microbial profiles. Here, we monitored the dynamics of short-chain fatty acid concentrations in common marmoset feces from the prepairing (PRE) to postpairing (POST) stages. In males, we observed that the concentrations of acetate, propionate, isobutyrate, and isovalerate significantly increased in the POST stage compared to the PRE stage. However, no significant changes were found in females. We further found that the propionate concentration was significantly positively correlated with the abundance of Phascolarctobacterium in the male feces. Thus, the sex difference in the changes in the concentrations of short-chain fatty acids might be related to sex-biased gut microbiome transmission after pairing. We suggest that the significant changes in the gut microbiomes and some short-chain fatty acids of the common marmoset during cohabitation may contribute to physiological homeostasis during pairing. IMPORTANCE This study addressed a knowledge gap about longitudinal changes in the gut microbiome metabolites during animal pairing. This research in the laboratory common marmoset can control for the confounding factors such as diet and other environmental conditions. Phascolarctobacterium showed the highest contribution to the sex-biased transmission of the female to the male after pairing. Here, we observed the sex difference in the increase in short-chain fatty acid concentration in the feces of newly paired marmosets, which may be caused by the sex-biased gut microbiome transmission after pairing.

Associations between gut microbiome, short chain fatty acids and blood pressure across ethnic groups: the HELIUS study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B Verhaar ◽  
D Collard ◽  
A Prodan ◽  
J.H.M Levels ◽  
A.H Zwinderman ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Fatty Acids ◽  
Ethnic Groups ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Funding Source ◽  
Microbiome Composition ◽  
Helius Study ◽  
Chain Fatty Acids

Abstract Background Gut microbiome composition is shaped by a combination of host genetic make-up and dietary habits. In addition, large ethnic differences exist in microbiome composition. Several studies in humans and animals have shown that differences in gut microbiota and its metabolites, including short chain fatty acids (SCFA), are associated with blood pressure (BP). We hypothesized that gut microbiome composition and its metabolites may be differently associated with BP across ethnic groups. Purpose To investigate associations of gut microbiome composition and fecal SCFA levels with BP across different ethnic groups. Methods We assessed the association between gut microbiome composition and office BP among 4672 subjects (mean age 49.8±11.7 years, 52%F) of 6 different ethnic groups participating in the HELIUS study. Gut microbiome composition was determined using 16S rRNA sequencing. Associations between microbiome composition and blood pressure were assessed using machine learning prediction models. The resulting best predictors were correlated with BP using Spearman's rank correlations. Fecal SCFA levels were measured with high-performance liquid chromatography in an age- and body mass index (BMI)-matched subgroup of 200 participants with either extreme low or high systolic BP. Differences in abundances of best predictors and fecal SCFA levels between high and low BP groups were assessed with Mann-Whitney U tests. Results Gut microbiome composition explained 4.4% of systolic BP variance. Best predictors for systolic BP included Roseburia spp. (ρ −0.15, p<0.001), Clostridium spp. (ρ −0.14, p<0.001), Romboutsia spp. (ρ −0.10, p<0.001), and Ruminococceae spp. (ρ −0.15, p<0.001) (Figure 1). Explained variance of the microbiome composition was highest in Dutch subjects (4.8%), but very low in African Surinamese, Ghanaian, and Turkish ethnic groups (ranging from 0–0.77%) Hence, we selected only participants with Dutch ethnicity for the matched subgroup. Participants with high BP had lower abundance of Roseburia hominis (p<0.01) and Roseburia spp. (p<0.05) compared to participants with low BP. However, fecal acetate (p<0.05) and propionate (p<0.01) levels were higher in participants with high BP. Conclusions In this cross-sectional study, gut microbiome composition was moderately associated with BP. Associations were strongly divergent between ethnic groups, with strongest associations in Dutch participants. Intriguingly, while Dutch participants with high BP had lower abundances of several SCFA-producing microbes, they had higher fecal SCFA levels. Intervention studies with SCFAs could provide more insight in the effects of these metabolites on BP. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): The Academic Medical Center (AMC) of Amsterdam and the Public Health Service of Amsterdam (GGD Amsterdam) provided core financial support for HELIUS. The HELIUS study is also funded by research grants of the Dutch Heart Foundation (Hartstichting; grant no. 2010T084), the Netherlands Organization for Health Research and Development (ZonMw; grant no. 200500003), the European Integration Fund (EIF; grant no. 2013EIF013) and the European Union (Seventh Framework Programme, FP-7; grant no. 278901).

Gut microbiome–short-chain fatty acids interplay in the context of iron deficiency anaemia

2021 ◽  
Author(s):  
Ana Soriano-Lerma ◽  
María García-Burgos ◽  
María J.M. Alférez ◽  
Virginia Pérez-Carrasco ◽  
Victoria Sanchez-Martin ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Iron Deficiency ◽  
Gut Microbiome ◽  
Iron Deficiency Anaemia ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Deficiency Anaemia ◽  
Chain Fatty Acids

Protective action of the microbial metabolite butyrate against cardiomyocyte hypertrophy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Umei ◽  
H Akazawa ◽  
A Saga-Kamo ◽  
H Yagi ◽  
Q Liu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Short Chain Fatty Acid ◽  
Short Chain Fatty Acids ◽  
Chain Fatty Acid ◽  
G Protein Coupled Receptors ◽  
Short Chain ◽  
Cardiomyocyte Hypertrophy ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome ◽  
G Protein Coupled

Abstract Introduction Short-chain fatty acids are one of the gut microbial metabolites that may influence host physiology. We previously reported that gut dysbiosis was associated with heart failure, and that the proportions of butyrate-producing bacteria diminished prominently in the gut of patients with heart failure. Purpose We investigated the molecular mechanism of butyrate and investigated the protective mechanism against heart failure. Methods We searched for G protein-coupled receptors for short-chain fatty acids using single-cell transcriptome analysis of cardiomyocytes and non-cardiomyocytes isolated from murine hearts. In addition, we examined the effects of butyrate on endothelin-1 (ET1) or isoproterenol-induced hypertrophic responses and histone deacetylase (HDAC) activities in cultured neonatal rat cardiomyocytes. Results Single-cell transcriptome analysis and co-expression network analysis revealed that G protein-coupled receptors for short-chain fatty acid receptors were not expressed in cardiomyocytes and that Olfr78 was expressed in vascular smooth muscle cells in the heart. Treatment with butyrate inhibited ET1-induced hypertrophic growth and up-regulation of the genes such as Nppa, Acta1, and Myh7 in cultured rat neonatal cardiomyocytes. Moreover, butyrate increased the acetylation levels of histone H3, indicating that butyrate has an inhibitory effect on HDAC in cardiomyocytes. In addition, treatment with butyrate caused up-regulation of Inpp5f, encoding inositol polyphosphate-5-phosphatase f, which was associated with a significant decrease in the phosphorylation levels of Akt. These results suggest that butyrate may act as HDAC inhibitor to increase Inpp5f gene expression, leading to the activation of Akt-glycogen synthase kinase 3beta (Gsk3beta) pathway, and thereby protect against hypertrophic responses. Conclusion There was no known GPCR for short-chain fatty acid expressed in cardiomyocytes. However, butyrate suppressed cardiomyocyte hypertrophy through epigenetic modification of gene expression. Our results may uncover a potential role of the dysbiosis of intestinal microbiota in the pathogenesis of cardiac hypertrophy and failure. Funding Acknowledgement Type of funding source: None

scholarly journals Ileal short-chain fatty acids inhibit gastric motility by a humoral pathway

2000 ◽  
Vol 279 (5) ◽  
pp. G925-G930 ◽  
Author(s):  
G. Cuche ◽  
J. C. Cuber ◽  
C. H. Malbert
Keyword(s):  
Gastric Motility ◽  
Short Chain Fatty Acid ◽  
Peptide Yy ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Maximal Amplitude ◽  
Inhibiting Factor ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

The aim of this study was to evaluate the nervous and humoral pathways involved in short-chain fatty acid (SCFA)-induced ileal brake in conscious pigs. The role of extrinsic ileal innervation was evaluated after SCFA infusion in innervated and denervated Babkin's ileal loops, and gastric motility was measured with strain gauges. Peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) concentrations were evaluated in both situations. The possible involvement of absorbed SCFA was tested by using intravenous infusion of acetate. Ileal SCFA infusion in the intact terminal ileum decreased the amplitude of distal and terminal antral contractions (33 ± 1.2 vs. 49 ± 1.2% of the maximal amplitude recorded before infusion) and increased their frequency (1.5 ± 0.11 vs. 1.3 ± 0.10/min). Similar effects were observed during SCFA infusion in ileal innervated and denervated loops (amplitude, 35 ± 1.0 and 34 ± 0.8 vs. 47 ± 1.3 and 43 ± 1.2%; frequency, 1.4 ± 0.07 and 1.6 ± 0.06 vs. 1.1 ± 0.14 and 1.0 ± 0.12/min). Intravenous acetate did not modify the amplitude and frequency of antral contractions. PYY but not GLP-1 concentrations were increased during SCFA infusion in innervated and denervated loops. In conclusion, ileal SCFA inhibit distal gastric motility by a humoral pathway involving the release of an inhibiting factor, which is likely PYY.

Abstract P485: Association of Hypertension With the Gut Microbiome and Serum Short-chain Fatty Acids

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Moira K Differding ◽  
Lawrence J Appel ◽  
Nisa Maruthur ◽  
Stephen Juraschek ◽  
Edgar R Miller ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Self Report ◽  
Short Chain ◽  
Inverse Association ◽  
Negatively Associated ◽  
Adult Cancer Survivors ◽  
Chain Fatty Acids

Background: Murine models indicate that gut microbiota, and the short chain fatty acids (SCFAs) they produce from fermentation of fiber, play a role in blood pressure (BP) regulation. However, few human studies have examined how gut microbiota and serum SCFAs are associated with hypertension. Objective: We examined associations of gut microbiota composition and serum SCFAs with hypertension and BP, hypothesizing an inverse association with serum SCFAs. Methods: We performed a cross-sectional analysis of baseline data from a trial of overweight and obese adult cancer survivors. We measured 1 ) the gut microbiome by extracting microbial DNA from stool and sequencing the 16S rRNA V4 region and 2 ) serum SCFA using liquid chromatography mass spectrometry. Hypertension was defined as systolic BP ≥ 130, diastolic BP ≥ 80 mmHg, self-report, or use of hypertension medications. We used beta-binomial models to test differential abundance of microbial amplicon sequence variants by hypertension , and linear regression to examine log-transformed SCFAs with BP. We adjusted models for age, sex, race, fiber, BMI and medications (in BP models). Results: Of 111 participants with complete data, 73 had hypertension. Hypertensive participants differed by age (mean 62 vs. 56y) and sex (73% vs. 90% female), but not race (46% black) or BMI (mean 35 kg/m 2 ). Alpha and beta diversity were not associated with hypertension (Ps>0.05). Hypertensive participants had higher abundance of Bacteroides, Parabacteroides, Bifidobacterium and Escherichia , and lower Lachnospiraceae, Haemophilus and Faecalibacterium ( Figure) . Serum acetate was negatively associated with systolic BP (β=-3.3 mmHg difference per 1 SD increment acetate, 95% CI: -6.1, -0.6); other SCFAs were not associated (Ps>0.05). Conclusion: A Bacteroides dominated microbiota was positively associated with hypertension. Acetate, the most abundant circulating SCFA, was negatively associated with BP. Determining whether the associations are causal or not warrants further investigation.

scholarly journals Gut Microbiome Modulation Based on Probiotic Application for Anti-Obesity: A Review on Efficacy and Validation

2019 ◽  
Vol 7 (10) ◽  
pp. 456 ◽  
Author(s):  
Kaliyan Barathikannan ◽  
Ramachandran Chelliah ◽  
Momna Rubab ◽  
Eric Banan-Mwine Daliri ◽  
Fazle Elahi ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Molecular Mechanisms ◽  
Short Chain Fatty Acids ◽  
Genetic Profile ◽  
Fecal Transplantation ◽  
Intestinal Microbes ◽  
Prevalence Of Obesity ◽  
Future Direction ◽  
The Impact

The growing prevalence of obesity has become an important problem worldwide as obesity has several health risks. Notably, factors such as excessive food consumption, a sedentary way of life, high sugar consumption, a fat-rich diet, and a certain genetic profile may lead to obesity. The present review brings together recent advances regarding the significance of interventions involving intestinal gut bacteria and host metabolic phenotypes. We assess important biological molecular mechanisms underlying the impact of gut microbiota on hosts including bile salt metabolism, short-chain fatty acids, and metabolic endotoxemia. Some previous studies have shown a link between microbiota and obesity, and associated disease reports have been documented. Thus, this review focuses on obesity and gut microbiota interactions and further develops the mechanism of the gut microbiome approach related to human obesity. Specifically, we highlight several alternative diet treatments including dietary changes and supplementation with probiotics. The future direction or comparative significance of fecal transplantation, synbiotics, and metabolomics as an approach to the modulation of intestinal microbes is also discussed.

scholarly journals Short Chain Fatty Acid Production from Mycoprotein and Mycoprotein Fibre in an In Vitro Fermentation Model

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 800 ◽  
Author(s):  
Hannah Harris ◽  
Christine Edwards ◽  
Douglas Morrison
Keyword(s):  
Energy Intake ◽  
Short Chain Fatty Acid ◽  
Short Chain Fatty Acids ◽  
Chain Fatty Acid ◽  
Fibre Content ◽  
Short Chain ◽  
Fatty Acid Production ◽  
In Vitro Fermentation ◽  
Fermentation Model

Dietary mycoprotein (marketed as QuornTM) has many health benefits, including reductions in energy intake. The majority of studies evaluating mycoprotein focus on the protein content and very few consider the fibre content. Fibre consumption is also associated with decreased energy intake, which is partly attributed to short chain fatty acids (SCFAs) from fibre fermentation by colonic bacteria. To study the SCFA-producing capability of mycoprotein, in vitro batch fermentations were conducted, and SCFA production compared with that from extracted mycoprotein fibre, oligofructose (OF), rhamnose, and laminarin. Mycoprotein and mycoprotein fibre were both fermentable, resulting in a total SCFA production of 24.9 (1.7) and 61.2 (15.7) mmol/L, respectively. OF led to a significantly higher proportion of acetate compared to all other substrates tested (92.6 (2.8)%, p < 0.01). Rhamnose generated the highest proportion of propionate (45.3 (2.0)%, p < 0.01), although mycoprotein and mycoprotein fibre yielded a higher proportion of propionate compared with OF and laminarin. Butyrate proportion was the highest with laminarin (28.0 (10.0)although mycoprotein fibre led to a significantly higher proportion than OF (p < 0.01). Mycoprotein is a valuable source of dietary protein, but its fibre content is also of interest. Further evaluation of the potential roles of the fibre content of mycoprotein is required.

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