Chronic low-dose oral methylglyoxal intake is associated with delayed circadian sleep timing and altered gut microbiota in mice.

Reactive carbonyls including methylglyoxal (MGO) in foodstuffs irreversibly modify proteins and generate advanced glycation end products (AGEs) that are considered toxic. On the other hand, it has also been suggested that chronic MGO consumption does not necessarily intensify renal insufficiency or modify protein AGEs. We compared the effects of drinking water without or with 1% MGO ad libitum for approximately 9 months on sleep parameters, circadian locomotor activity, and gut microbiota in mice. Plasma AGE levels transiently increased after 3 weeks then returned to baseline. Electroencephalographic findings revealed that MGO significantly delayed the circadian phase of non-rapid eye movement (NREM) and REM sleep without affecting the total daily durations of these sleep stages. The total daily amounts and diurnal rhythms of wheel-running activity under light/dark conditions were similar between the groups, whereas MGO slightly, but not significantly extended the free-running period under constant darkness. The Firmicutes-to-Bacteroidetes ratio, a marker of gut dysbiosis, was increased >1.6-fold by MGO. Lactobacillus abundance increased >45-fold, which may reflect an adaptive microbial response to chronic MGO exposure. Thus, chronic low-dose MGO intake was associated with delayed circadian sleep onset and alterations in gut microbiota composition in mice, although a direct causal relationship between these phenomena remains unclear.