Delivery of Acetate to the Peripheral Blood after Consumption of Foods High in Short‐Chain Fatty Acids

Gill, Paul; Bogatyrev, A N; Zelm, Menno C. van; Muir, Jane G.

doi:10.1002/mnfr.202000953

Cited by 16 publications

(28 citation statements)

References 47 publications

(55 reference statements)

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“…These findings are consistent with a 5-day high fibre intervention, which did not change the frequencies of T cells in healthy participants. 15 However, although of borderline significance, HAMSAB reduced another well-known factor that regulates BP: total peripheral resistance. This is consistent with findings in experimental hypertension.…”

Section: Discussionmentioning

confidence: 99%

“…A significant challenge in translating these findings has been the sustained delivery of SCFAs over a long period. 15…”

Section: Introductionmentioning

confidence: 99%

“…A significant challenge in translating these findings has been the sustained delivery of SCFAs over a long period. 15 We hypothesised that increased production of gut microbiota-derived metabolites acetate and butyrate reduce BP in untreated hypertensive patients. To overcome the challenge of delivering these SCFAs to the systemic circulation, we used high amylose maize starch (HAMS), a type of resistant starch II that can be acetylated (HAMSA) and butyrylated (HAMSB).…”

Section: Introductionmentioning

confidence: 99%

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Gut microbial metabolites lower 24-hour systolic blood pressure in untreated essential hypertensive patients

Jama

Rhys-Jones

Nakai

et al. 2022

Preprint

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BackgroundFibres remain undigested until they reach the colon, where some are fermented by gut microbiota, producing metabolites called short-chain fatty acids (SCFAs). SCFAs lower blood pressure (BP) of experimental models, but their translational potential is unknown. We aimed to determine whether SCFAs lower 24-hour systolic BP (SBP) in untreated participants with essential hypertension.MethodsWe performed a phase II randomized placebo-controlled double-blind cross-over trial using SCFA-supplementation, delivered as acetylated and butyrylated high amylose maize starch (HAMSAB). Twenty treatment-naïve hypertensive participants were recruited from the community and randomised to 40g/day of HAMSAB or placebo. Participants completed each arm for three-weeks, with a three-week washout period between them. The primary endpoint was a 24-hour SBP decrease.ResultsParticipants were on average 55.8±11.2-years old (mean±SD), had a body mass index (BMI) of 25.7±2.5km2/m, 30% were female, baseline 24-hour SBP 136±6mmHg. No adverse effects were reported. After the intervention, the placebo-subtracted reduction in 24-hour SBP was 6.1±9.9mmHg (P= 0.027). This was independent of age, sex, BMI and study arm. There was no statistical significance in the placebo arm. Day and night SBP were reduced by 6.5±12.3mmHg (P=0.01) and 5.7±9.8mmHg (P=0.02), respectively, and 24-h central SBP by 7.2±14.7 mmHg (P=0.005). HAMSAB increased levels of acetate and butyrate by 7.8-fold (P=0.016), shifted the microbial ecosystem, and expanded the prevalence of SCFA-producers.ConclusionsWe observed a clinically relevant reduction in 24-hour SBP in participants with essential hypertension treated with the gut microbial-derived metabolites acetate and butyrate. These metabolites may represent a novel option for lowering BP.

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Section: Discussionmentioning

confidence: 99%

“…A significant challenge in translating these findings has been the sustained delivery of SCFAs over a long period. 15…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Gut microbial metabolites lower 24-hour systolic blood pressure in untreated essential hypertensive patients

Jama

Rhys-Jones

Nakai

et al. 2022

Preprint

View full text Add to dashboard Cite

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“…Indeed, fermented foods contain a wide range of compounds with immunomodulatory properties when exposed to cells in vitro ( Figure 3 ) ( 213 , 286 – 292 ). Consumption of fermented foods could deliver immune-modulatory compounds such as SCFA systemically, particularly if consumed multiple times per day ( 293 ). They also contain a diverse range of probiotic bacteria that initiate fermentation, such as lactic acid bacteria, acetic acid bacteria and Bacillus species [reviewed elsewhere ( 294 )].…”

Section: Utilising Dietary Therapy In the Treatment Of Human Gastroin...mentioning

confidence: 99%

The Role of Diet and Gut Microbiota in Regulating Gastrointestinal and Inflammatory Disease

et al. 2022

Self Cite

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Diet is an important lifestyle factor that is known to contribute in the development of human disease. It is well established that poor diet plays an active role in exacerbating metabolic diseases, such as obesity, diabetes and hypertension. Our understanding of how the immune system drives chronic inflammation and disease pathogenesis has evolved in recent years. However, the contribution of dietary factors to inflammatory conditions such as inflammatory bowel disease, multiple sclerosis and arthritis remain poorly defined. A western diet has been associated as pro-inflammatory, in contrast to traditional dietary patterns that are associated as being anti-inflammatory. This may be due to direct effects of nutrients on immune cell function. Diet may also affect the composition and function of gut microbiota, which consequently affects immunity. In animal models of inflammatory disease, diet may modulate inflammation in the gastrointestinal tract and in other peripheral sites. Despite limitations of animal models, there is now emerging evidence to show that anti-inflammatory effects of diet may translate to human gastrointestinal and inflammatory diseases. However, appropriately designed, larger clinical studies must be conducted to confirm the therapeutic benefit of dietary therapy.

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“… SCFA, short-chain fatty acids; MCFA, medium-chain fatty acids; LCFA, long-chain fatty acids ( 20 – 23 ) . …”

Section: Cardiac Metabolism Of the Healthy Physiological Heartmentioning

confidence: 99%

Short-Chain Fatty Acids in the Metabolism of Heart Failure – Rethinking the Fat Stigma

Palm

Nijholt

Bakker

et al. 2022

Front. Cardiovasc. Med.

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Heart failure (HF) remains a disease with immense global health burden. During the development of HF, the myocardium and therefore cardiac metabolism undergoes specific changes, with decreased long-chain fatty acid oxidation and increased anaerobic glycolysis, diminishing the overall energy yield. Based on the dogma that the failing heart is oxygen-deprived and on the fact that carbohydrates are more oxygen-efficient than FA, metabolic HF drugs have so far aimed to stimulate glucose oxidation or inhibit FA oxidation. Unfortunately, these treatments have failed to provide meaningful clinical benefits. We believe it is time to rethink the concept that fat is harmful to the failing heart. In this review we discuss accumulating evidence that short-chain fatty acids (SCFAs) may be an effective fuel for the failing heart. In contrast to long-chain fatty acids, SCFAs are readily taken up and oxidized by the heart and could serve as a nutraceutical treatment strategy. In addition, we discuss how SCFAs activate pathways that increase long chain fatty acid oxidation, which could help increase the overall energy availability. Another potential beneficial effect we discuss lies within the anti-inflammatory effect of SCFAs, which has shown to inhibit cardiac fibrosis – a key pathological process in the development of HF.

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Delivery of Acetate to the Peripheral Blood after Consumption of Foods High in Short‐Chain Fatty Acids

Cited by 16 publications

References 47 publications

Gut microbial metabolites lower 24-hour systolic blood pressure in untreated essential hypertensive patients

Gut microbial metabolites lower 24-hour systolic blood pressure in untreated essential hypertensive patients

The Role of Diet and Gut Microbiota in Regulating Gastrointestinal and Inflammatory Disease

Short-Chain Fatty Acids in the Metabolism of Heart Failure – Rethinking the Fat Stigma

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