Microbiota-dependent increase in δ-valerobetaine alters neuronal function and is responsible for age-related cognitive decline

Diet- and microbiota-related metabolite, 5-aminovaleric acid betaine (5-AVAB), in health and disease

“…However, 5-AVAB could be biosynthesized utilizing methyl groups originating from glycine betaine and play a critical role in fetal growth, similar to glycine betaine [56,57], and/or protect the neurodevelopment of the fetus as has been shown for a high choline intake during gestation in mice and rat experiments [58]. Interestingly, a very recent article claimed that the extent of the increase in 5-AVAB concentration correlated positively with age-related cognitive decline [59], further strengthening the evidence that this compound is a significant mediator in the gut-brain axis, although its precise role has yet to be established.…”

Small molecules in the big picture of gut microbiome-host cross-talk

“… 12 Recently, an additional microbiome-derived metabolite δ-valerobetaine (TMAVA), a trimethylamine N-oxide (TMAO) structural analogue, was indicated to be a diet-dependent obesogen that could exacerbate obesity in mice induced by the western diet. 13 Moreover, studies have shown that gut microbial metabolites can influence insulin resistance. Specifically, SCFAs-induced improvements in adipose tissue metabolism can prevent insulin resistance, while succinate improves the host insulin sensitivity while preventing obesity.…”

The Gut–Immune–Brain Axis: An Important Route for Neuropsychiatric Morbidity in Inflammatory Bowel Disease

“…The phenolic compounds phenyl sulfate, pyrocatechol sulfate, and 3-(3-sulfooxyphenyl)propanoic acid as well as indoxyl sulfate were implicated in synaptic remodeling and fear extinction learning [ 161 ]. Moreover, δ-valerobetaine produced by diverse bacterial species modulates inhibitory synaptic transmission and neuronal network activity independent of microglia, preventing age-related decline in cognitive function [ 162 ]. SCFAs are able to act locally in the ENS and enhance enteric neuronal survival and neurogenesis potentially acting via the 5-hydroxytryptamine type 4 (5-HT4) receptor [ 163 ].…”