Short-chain fatty acids as a link between diet and cardiometabolic risk: a narrative review

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TL;DR

This narrative review summarizes evidence that dietary fibers are fermented by gut microbiota into short-chain fatty acids (SCFAs), which may modulate cardiometabolic risk through effects on inflammation, appetite, blood glucose, lipid metabolism, and blood pressure. High-fiber diets are associated with increased SCFA-producing bacteria and favorable metabolic profiles, while high-fat diets (especially those rich in saturated fatty acids) are linked to dysbiosis and adverse outcomes. The authors conclude that current evidence supports dietary guidelines emphasizing plant-based foods, but note that individual factors such as age, sex, ethnicity, genetics, and baseline gut microbiota influence metabolic responses to diet.

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**Background:** Diet has a well-established role in cardiometabolic health, and the gut microbiota has emerged as a potential mediator of dietary effects on obesity, insulin resistance, and cardiovascular disease. Short-chain fatty acids (SCFAs)—primarily acetate, propionate, and butyrate—are produced when gut bacteria ferment indigestible dietary fibers. This narrative review summarizes current knowledge on the interaction between diet and gut microbiota, focusing on SCFAs and their role in modulating cardiometabolic risk.

**Methods:** The authors conducted a narrative (non-systematic) review, selecting publications on a discretionary basis for relevance. Searches were performed in PubMed and Google Scholar from May 2021 to July 2022 using keywords including diet, short-chain fatty acids, gut microbiota, gut bacteria, cardiometabolic, prebiotics, SCFA receptors, LPS, and inflammation. Additional articles were identified via snowballing. The review focused on human studies but included animal and cell-line studies where human data were lacking.

**Key Results:** Observational and interventional studies consistently show that diets rich in fiber or supplemented with prebiotic fibers (e.g., inulin-type fructans [ITF], galacto-oligosaccharides [GOS], β-glucan) increase gut microbiota diversity and SCFA-producing bacteria. For example, wheat bran supplementation (>70% arabinoxylan oligosaccharides) increased butyrate, acetate, and propionate concentrations. A systematic review and meta-analysis in type 2 diabetes found that dietary fiber improved relative abundance of Bifidobacterium and total SCFA, and improved glycated hemoglobin. Three days of barley-kernel bread rich in β-glucan increased serum SCFA and gut hormones (GLP-1, PYY, GLP-2) and improved insulin sensitivity. High-fat diets, particularly those rich in saturated fatty acids, are associated with reduced bacterial abundance, diversity, and richness. In a 6-month controlled feeding trial among 217 young healthy adults, a high-fat diet (40% energy from fat) had unfavorable effects on gut microbiota, fecal bacterial metabolites, and inflammatory markers, whereas a lower-fat diet (20% energy from fat) was associated with a more favorable profile. The PREDICT study (over 1000 participants) found that gut microbiota explained 7.1% of variance in postprandial lipidemia (vs. 3.6% for macronutrient composition) and 6% of variance in postprandial glycemia (vs. 15.4% for macronutrients). Genetic variations only partially influenced predictions (9.5% for glucose, 0.8% for triglycerides, 0.2% for C-peptide). A Dutch study of 1425 individuals found that processed and animal-derived foods were associated with higher abundances of Firmicutes, Ruminococcus species, and endotoxin synthesis pathways, while plant foods and fish correlated positively with SCFA-producing bacteria. SCFAs exert anti-inflammatory effects via G protein-coupled receptors (GPR41, GPR43, GPR109, Olfr78), reduce intestinal permeability and endotoxemia, and stimulate release of gut hormones (GLP-1, GLP-2, PYY) that improve glycemic control and appetite regulation. Propionate supplementation in humans has been shown to reduce energy intake and protect against weight gain. However, human intervention studies with ITF (16 g/day for 6 weeks) in patients with type 2 diabetes showed increased fecal SCFA but no positive effect on glucose, insulin, gut hormones, appetite, or energy intake.

**Clinical Implications:** The findings support current dietary guidelines encouraging fiber-rich plant-based foods and discouraging high intake of animal foods rich in saturated fatty acids. However, metabolic responses to dietary interventions vary depending on individual traits such as age, sex, ethnicity, existing gut microbiota, and genetics. The authors note that most human intervention studies are acute or short-term (3–12 weeks) with small sample sizes (n=6–30), and that fecal SCFA measurements may underestimate true production since most SCFA are absorbed in the colon. Future research requires better dietary assessment methods, improved microbiota classification techniques, and large, long-term human intervention studies across diverse populations to establish causality and develop personalized dietary recommendations.