Metformin Affects Gut Microbiome Composition and Function and Circulating Short-Chain Fatty Acids: A Randomized Trial

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).

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

European Journal of Nutrition ◽

10.1007/s00394-021-02645-6 ◽

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

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

Circulation ◽

10.1161/circ.141.suppl_1.p485 ◽

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.

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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)

Current Developments in Nutrition ◽

10.1093/cdn/nzz030.p05-017-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Cited By ~ 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.

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Modified Mediterranean-ketogenic diet modulates gut microbiome and short-chain fatty acids in association with Alzheimer's disease markers in subjects with mild cognitive impairment

EBioMedicine ◽

10.1016/j.ebiom.2019.08.032 ◽

2019 ◽

Vol 47 ◽

pp. 529-542 ◽

Cited By ~ 42

Author(s):

Ravinder Nagpal ◽

Bryan J. Neth ◽

Shaohua Wang ◽

Suzanne Craft ◽

Hariom Yadav

Keyword(s):

Alzheimer’S Disease ◽

Fatty Acids ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Ketogenic Diet ◽

Gut Microbiome ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Disease Markers ◽

Chain Fatty Acids

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

mSphere ◽

10.1128/msphere.00794-20 ◽

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.

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Short-Chain Fatty Acids

10.32545/encyclopedia202005.0006.v2 ◽

2020 ◽

Author(s):

Paulina Markowiak-Kopeć ◽

Katarzyna Śliżewska

Keyword(s):

Fatty Acids ◽

Volatile Fatty Acids ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Intestinal Microbiome ◽

Test Results ◽

And Function ◽

The Relationship ◽

Normal Health ◽

Chain Fatty Acids

The relationship between diet and the diversity and function of the intestinal microbiomeand its importance for human health is currently the subject of many studies. The type and proportionof microorganisms found in the intestines can determine the energy balance of the host. Intestinalmicroorganisms perform many important functions, one of which is participation in metabolicprocesses, e.g., in the production of short-chain fatty acids—SCFAs (also called volatile fatty acids).These acids represent the main carbon flow from the diet to the host microbiome. Maintainingintestinal balance is necessary to maintain the host’s normal health and prevent many diseases.The results of many studies confirm the beneficial effect of probiotic microorganisms on the balanceof the intestinal microbiome and produced metabolites, including SCFAs. The aim of this review is tosummarize what is known on the effects of probiotics on the production of short-chain fatty acidsby gut microbes. In addition, the mechanism of formation and properties of these metabolites isdiscussed and verified test results confirming the effectiveness of probiotics in human nutrition bymodulating SCFAs production by intestinal microbiome is presented.

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MP03-11 GUT MICROBIOME AND SHORT CHAIN FATTY ACIDS IN RENAL CALCIUM OXALATE STONES FORMATION

The Journal of Urology ◽

10.1097/01.ju.0000554943.49324.a5 ◽

2019 ◽

Vol 201 (Supplement 4) ◽

Author(s):

Kunjie Wang* ◽

Yu Liu ◽

Liang Zhou ◽

Yi Li ◽

Qun Sun ◽

...

Keyword(s):

Fatty Acids ◽

Calcium Oxalate ◽

Gut Microbiome ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Calcium Oxalate Stones ◽

Chain Fatty Acids

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Short chain fatty acids (SCFA), the products of gut bacteria metabolism and their role in the host

Postępy Higieny i Medycyny Doświadczalnej ◽

10.5604/01.3001.0011.6468 ◽

2018 ◽

Vol 72 ◽

pp. 131-142 ◽

Cited By ~ 7

Author(s):

Aleksandra Czajkowska ◽

Bogumiła Szponar

Keyword(s):

Fatty Acids ◽

Immune System ◽

Short Chain Fatty Acids ◽

Gastrointestinal Diseases ◽

Bacterial Consortium ◽

Treg Cells ◽

Short Chain ◽

Microbiome Composition ◽

Promising Tool ◽

Chain Fatty Acids

Gut bacterial consortium is essential for the homeostasis of the immune system in mammals. A significant role in maintaining this balance play short-chain fatty acids (SCFA), bacterial metabolites resulting from fermentation of dietary oligosaccharides. The most significant are butyric, propionic and acetic acids present in the microbiome in a specified mole ratio, but these proportions may change due to diet, age, diseases, and other factors. SCFA are the type of messengers between microbiota and immune system. They are responsible for maintaining the balance in the pro- and anti-inflammatory reaction through the set of free fatty acid receptors (GPR). Short chain fatty acids may induce regulatory T-cells (Treg) by an bakteinhibition of histone deacetylase enzyme; the biggest inhibitory potential has butyric acid, causing proliferation and an increase of the functional capabilities of Treg cells. Manipulation of the gut microbiome composition and SCFA level constitutes a promising tool supporting treatment of chronic gastrointestinal diseases associated with an inflammation or caused by dysbiosis due to intensive use of antibiotics.

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