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 Muscadine Grape Extract Reduces Lung and Liver Metastasis in Mice with Triple Negative Breast Cancer in Association with Changes in the Gut Microbiome (P05-017-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Marianne Collard ◽  
Nataleigh Austin ◽  
Ann Tallant ◽  
Patricia Gallagher
Keyword(s):  
Breast Cancer ◽  
Fatty Acids ◽  
Gut Microbiota ◽  
Triple Negative Breast Cancer ◽  
Gut Microbiome ◽  
Triple Negative ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Muscadine Grape ◽  
Chain Fatty Acids

Abstract Objectives The goal of this study was to determine if a proprietary muscadine grape seed and skin extract (MGE) inhibits triple negative breast cancer (TNBC) metastasis and alters the gut microbiota. Methods 4T1 TNBC cells were injected into the mammary fat pad of 6-week-old female Balb/c mice. After 2 weeks, tumors were surgically removed and mice were placed into a control group (n = 8) or a treatment group that received 0.1 mg/mL total phenolics MGE (Piedmont R&D) in the drinking water (n = 8). Mice were sacrificed after 4 weeks; tissues and fecal samples were collected for analysis. Immunohistochemistry (Ki67, α-SMA) and hemotoxylin and eosin staining were used to quantify metastases using the inForm© 2.2 software. Gut microbial composition was determined by 16S rRNA sequencing and short chain fatty acids were detected by gas chromatography (Microbiome Insights). Data are expressed as means ± SEM using student's t-test. Results MGE reduced Ki67 cell positivity in the lungs and livers of mice, indicating reduced metastatic proliferation (9.3 ± 0.9% vs 6.2 ± 0.7% and 5.0 ± 1.5% vs 0.77 ± 0.2% cells, respectively; P < 0.01), and decreased cancer associated fibroblasts in the lungs (5.3 ± 1.0% vs 3.0 ± 0.5% cells; P < 0.05), which are associated with metastasis. MGE significantly reduced the number (4.7 ± 0.7 vs 2.2 ± 0.4 tumors/field; P < 0.01) and size (1358 ± 48 vs 1121 ± 47 pixels; P < 0.01) of liver metastases, resulting in decreased metastatic tumor burden (6656 ± 1220 vs 3096 ± 644 total area in pixels; P < 0.01). Attenuated TNBC metastasis correlated with MGE-induced changes in gut microbiota. Alpha diversity (4.15 ± 0.10 vs 4.51 ± 0.13 Shannon index; P < 0.05) and the Firmicutes to Bacteroidetes ratio (0.37 ± 0.07 vs 0.76 ± 0.12; P < 0.05) were significantly increased in MGE-treated mice, indicating enhanced microbial richness and increased energy harvest by the gut microbiome. Butyrate-producing bacteria, such as Ruminococcus, Butyricicoccus and Lachnospiraceae, were increased with MGE (P < 0.05) as well as the anti-inflammatory compound butyrate relative to other short-chain fatty acids (25.0 ± 2.7% vs 75.3 ± 15.5%; P < 0.01). Conclusions These data show that MGE attenuates TNBC metastasis in association with alterations in the gut microbiome, suggesting that MGE may be an effective treatment against TNBC metastatic progression. Funding Sources Chronic Disease Research Fund.

scholarly journals Lung Immune Tone via Gut-Lung Axis: Gut-derived LPS and Short-chain Fatty Acids' immunometabolic regulation of Lung IL-1β, FFAR2 and FFAR3 Expression

2021 ◽  
Author(s):  
Qing Liu ◽  
Xiaoli Tian ◽  
Daisuke Maruyama ◽  
Mehrdad Arjomandi ◽  
Arun Prakash
Keyword(s):  
Fatty Acids ◽  
Gut Microbiota ◽  
Lung Tissue ◽  
Gut Microbiome ◽  
Human Lung ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Human Lung Tissue ◽  
Chain Fatty Acids

Microbial metabolites produced by the gut microbiome, e.g. short-chain fatty acids (SCFA), have been found to influence lung physiology and injury responses. However, how lung immune activity is regulated by SCFA is unknown. We examined fresh human lung tissue and observed the presence of SCFA with inter-individual variability. In vitro, SCFA were capable of modifying the metabolic programming in LPS-exposed alveolar macrophages (AM). We hypothesized that lung immune tone could be defined by baseline detection of lung intracellular IL-1β. Therefore, we interrogated naïve mouse lungs with intact gut microbiota for IL-1β mRNA expression and localized its presence within alveolar spaces, specifically within AM subsets. We established that metabolically active gut microbiota, that produce SCFA, can transmit LPS and SCFA to the lung and thereby could create primed lung immunometabolic tone. To understand how murine lung cells sensed and upregulated IL-1β in response to gut microbiome-derived factors, we determined that, in vitro, AM and AT2 cells expressed SCFA receptors, FFAR2, FFAR3, and IL-1β but with distinct expression patterns and different responses to LPS. Finally, we observed that IL-1β, FFAR2 and FFAR3 were expressed in isolated human AM and AT2 cells ex-vivo, but in fresh human lung sections in situ, only AM expressed IL-1β at rest and after LPS challenge. Together, this translational study using mouse and human lung tissue and cells point to an important role for the gut microbiome and their SCFA in establishing and regulating lung immune tone.

The Consumption of Galactomannan Effervescent Drinks made from Coconut Pulp Waste and Colonic Microbiota in Wistar Rats

2020 ◽  
Vol 15 (1) ◽  
pp. 52-56
Author(s):  
Sri Winarti ◽  
Agung Pasetyo
Keyword(s):  
Fatty Acids ◽  
Gut Microbiota ◽  
Wistar Rats ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
E Coli ◽  
Colonic Microbiota ◽  
Male Wistar Rats ◽  
Lactobacillus Spp ◽  
Chain Fatty Acids

The consumption of prebiotics is known to affect the balance of gut microbiota. The purpose of this study was to explore how a galactomannan-rich effervescent drink can affect the population of Lactobacillus, Bifidobacterium, E. coli, and the concentration of short-chain fatty acids in the cecum of rats. Twenty-eight male Wistar rats (aged 2 months) were divided equally into 7 groups and treated orally each day for 15 days with 2 mL effervescent drinks with increasing levels of prebiotic galactomannan. The dosage of 500 mg galactomannan increased the growth of Lactobacillus spp. and Bifidobacterium spp. with inhibition of the growth of E.coli with increased formation of short-chain fatty acids such as acetate, propionate, and butyrate in the cecum of rats.

Impact of oral COMT-inhibitors on gut microbiota and short chain fatty acids in Parkinson's disease

2020 ◽  
Vol 70 ◽  
pp. 20-22 ◽  
Author(s):  
Daniel Grün ◽  
Valerie C. Zimmer ◽  
Jil Kauffmann ◽  
Jörg Spiegel ◽  
Ulrich Dillmann ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Fatty Acids ◽  
Parkinson's Disease ◽  
Gut Microbiota ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Comt Inhibitors ◽  
Chain Fatty Acids

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&lt;0.001), Clostridium spp. (ρ −0.14, p&lt;0.001), Romboutsia spp. (ρ −0.10, p&lt;0.001), and Ruminococceae spp. (ρ −0.15, p&lt;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&lt;0.01) and Roseburia spp. (p&lt;0.05) compared to participants with low BP. However, fecal acetate (p&lt;0.05) and propionate (p&lt;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

scholarly journals Glycerol Monocaprylate Modulates Gut Microbiota and Increases Short-Chain Fatty Acids Production without Adverse Effects on Metabolism and Inflammation

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1427
Author(s):  
Junhui Zhang ◽  
Fengqin Feng ◽  
Minjie Zhao
Keyword(s):  
Fatty Acids ◽  
Gut Microbiota ◽  
Dose Group ◽  
Low Dose ◽  
Short Chain Fatty Acids ◽  
Normal Diet ◽  
Short Chain ◽  
High Dose ◽  
Dose Treatment ◽  
Chain Fatty Acids

Glycerol monocaprylate (GMC) is a glycerol derivative of medium-chain fatty acids (MCFAs) and is widely used as a preservative in food processing. However, GMC and its hydrolytic acid (octylic acid) have antibacterial properties that may affect the physiology and intestinal microecology of the human body. Therefore, in this study, the effects of two different dosages of GMC (150 and 1600 mg kg−1) on glucose, lipid metabolism, inflammation, and intestinal microecology of normal diet-fed C57BL/6 mice were comprehensively investigated. The obtained results showed that the level of triglycerides (TGs) in the low-dose group down-regulated significantly, and the anti-inflammatory cytokine interleukin 10 (IL-10) significantly increased, while the pro-inflammatory cytokines monocyte chemotactic protein 1 (MCP-1) and interleukin 1beta (IL-1β) in the high-dose group were significantly decreased. Importantly, GMC promoted the α-diversity of gut microbiota in normal-diet-fed mice, regardless of dosages. Additionally, it was found that the low-dose treatment of GMC significantly increased the abundance of Lactobacillus, while the high-dose treatment of GMC significantly increased the abundance of SCFA-producers such as Clostridiales, Lachnospiraceae, and Ruminococcus. Moreover, the content of short-chain fatty acids (SCFAs) was significantly increased by GMC supplementation. Thus, our research provides a novel insight into the effects of GMC on gut microbiota and physiological characteristics.

scholarly journals Relationships of gut microbiota, short-chain fatty acids, inflammation, and the gut barrier in Parkinson’s disease

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Velma T. E. Aho ◽  
Madelyn C. Houser ◽  
Pedro A. B. Pereira ◽  
Jianjun Chang ◽  
Knut Rudi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Fatty Acids ◽  
Parkinson's Disease ◽  
Gut Microbiota ◽  
Inflammatory Responses ◽  
Disease Onset ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Dependent Manner ◽  
Chain Fatty Acids

Abstract Background Previous 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. Methods Stool 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. Results Calprotectin 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. Conclusions Intestinal 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.

scholarly journals The relationship between gut microbiota, short-chain fatty acids and type 2 diabetes mellitus: the possible role of dietary fibre

2021 ◽  
Author(s):  
Dominic Salamone ◽  
Angela Albarosa Rivellese ◽  
Claudia Vetrani
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Gut Microbiota ◽  
Dietary Fibre ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Microbiota Composition ◽  
The Relationship ◽  
Chain Fatty Acids

AbstractGut microbiota and its metabolites have been shown to influence multiple physiological mechanisms related to human health. Among microbial metabolites, short-chain fatty acids (SCFA) are modulators of different metabolic pathways. On the other hand, several studies suggested that diet might influence gut microbiota composition and activity thus modulating the risk of metabolic disease, i.e. obesity, insulin resistance and type 2 diabetes. Among dietary component, dietary fibre may play a pivotal role by virtue of its prebiotic effect on fibre-fermenting bacteria, that may increase SCFA production. The aim of this review was to summarize and discuss current knowledge on the impact of dietary fibre as modulator of the relationship between glucose metabolism and microbiota composition in humans. More specifically, we analysed evidence from observational studies and randomized nutritional intervention investigating the relationship between gut microbiota, short-chain fatty acids and glucose metabolism. The possible mechanisms behind this association were also discussed.

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