hide
Free keywords:
-
Abstract:
Baby mammals produce the enzyme lactase, that cleaves the milk sugar lactose, until production stops with the cessation of lactation. A subset of humans have evolved lactase persistence (LP) into adulthood. LP confers lactose tolerance, allowing milk digestion in adults. One key aspect of lactose tolerance is low levels of H 2 gas production from lactose ingestion. Intriguingly, many lactase non-persistent (LNP) individuals also exhibit low levels of H 2 production from lactose (termed "acquired lactose tolerance", ALT). Although the microbiome is suspected to play a role in ALT, studies to date have failed to associate specific microbiota with ALT. Here, to identify microbiota that confer ALT, we assessed lactose tolerance (blood glucose and breath H2 monitored after lactose dose), LP/LNP genotype, and microbiome metagenomic diversity in adult volunteers (Gabon n=152, 0% LP; Vietnam n=190, 0.5% LP; Germany n=141, 77% LP). In each country, ~20% of LNP individuals exhibited ALT (breath H 2 rise below 30 ppm). In accord with previous studies, no metagenome differences were detected between microbiomes of lactose intolerant and ALT individuals. To better understand how lactose is metabolized in the gut of lactose intolerant versus ALT individuals, we added lactose to the stool in vitro and measured metabolite production. We found that stool could be sorted into 4 groups based on response to lactose: (1) inactive - lactose hydrolysis only; (2) weak - lactose hydrolysis with little fermentation; (3) gassy - lactose hydrolysis, fermentation and high H 2 production; and (4) tolerant - lactose hydrolysis, fermentation and low H 2. This result implies that ALT results from two distinct processes: low metabolic activity, or high metabolic activity resulting in low gas production. Using this classification for the metagenomes, we observed that Bifidobacteria were enriched in the tolerant group compared to the others. The tolerant group was also enriched in lactate and acetate, metabolic byproducts of the Bifid shunt. Our results indicate that ALT is prevalent across populations, including where the LP genotype is rare, and can result from two distinct processes. For metabolically- active microbiomes, the Bifidobacteria are the key microbiota conferring ALT. These findings indicate that Bifidobacterial-conferred ALT is widespread, and that by facilitating the digestion of lactose, may have enabled the incorporation of milk into the adult diet and the evolution of LP.
