Betaine

Betaine (trimethylglycine), a naturally occurring osmoprotectant and methyl donor, demonstrates anti‑inflammatory actions in numerous disease models. Mechanistically, betaine improves sulfur amino acid metabolism to counter oxidative stress, inhibits NF‑κB activity and NLRP3 inflammasome activation, regulates energy metabolism, and mitigates endoplasmic reticulum stress and apoptosis. Consequently, betaine has shown beneficial effects in obesity, diabetes, cancer, Alzheimer’s disease, and other conditions. The authors present betaine as a pleiotropic agent whose diverse molecular targets make it a promising candidate for further therapeutic development.

Fig. 1 Primary anti-inflammatory mechanisms of betaine. (Zhao G, et al., 2018)

In high‑fat diet‑fed mice, betaine supplementation enriched anti‑obesity gut bacteria (Akkermansia muciniphila, Lactobacillus, Bifidobacterium) and increased short‑chain fatty acids (acetate, butyrate). These SCFAs regulated DNA methylation at the miR‑378a promoter, and miR‑378a targeted YY1. Betaine’s protective effects were diminished in germ‑free mice. Thus, betaine acts through a gut microbiota → SCFAs → miR‑378a → YY1 regulatory axis to prevent obesity and metabolic syndrome, revealing a novel host‑microbiota interaction.

Fig. 2 Gut microbiota are involved in obesity prevention by betaine. (Du J, et al., 2021)