Can low-fiber diets reduce gut microbial diversity and increase TMA production?

A low-fiber dietary pattern fundamentally remodels the gut microbiome, which carries significant implications for systemic cardiovascular and metabolic health.

Microbial diversity and taxonomic shifts

• Depleting dietary fiber starves beneficial, saccharolytic taxa that rely on microbiota-accessible carbohydrates (MACs).
• This starvation causes a robust decline in microbial richness, depleting key short-chain fatty acid (SCFA)-producing lineages such as Bacteroidales, Prevotellaceae, Muribaculaceae, and Bifidobacterium.
• Concurrently, the lack of fiber promotes the expansion of mucin-degrading opportunists like Akkermansia muciniphila and pro-inflammatory taxa like Desulfovibrio, which consume host mucus.

Mechanistic pathways of TMA production

• Diets low in fiber and high in animal products select for taxa within the Firmicutes and Proteobacteria phyla that carry cutC/D (choline TMA-lyase) and cntA/B (carnitine monooxygenase) gene clusters.
• The bacterial cutC gene encodes a glycyl radical enzyme that obligatorily cleaves dietary choline to produce trimethylamine (TMA). This TMA is absorbed and subsequently oxidized in the liver to form the cardiovascular risk marker trimethylamine N-oxide (TMAO).
• Conversely, clinical evidence shows that dietary fiber supplementation downregulates the abundance and expression of these TMA-producing lyase genes, reducing TMA and TMAO metabolism by approximately 40% to 60% by allowing saccharolytic taxa to outcompete TMA-producing strains.

Bottom line

• Low-fiber diets systematically deplete beneficial, SCFA-producing microbial diversity while upregulating key bacterial lyase genes (cutC/D and cntA/B), directly driving increased microbial synthesis of the pro-atherogenic precursor TMA from dietary choline and carnitine.