Impact of short-chain galactooligosaccharides on the gut microbiome of lactose-intolerant individuals

Abstract

<p id="d11100181e339">Approximately 75% of the global human population are lactose malabsorbers. In a previous clinical trial, it was shown that feeding a high-purity galactooligosaccharide (&gt;95% GOS) could improve symptoms of lactose-intolerant subjects, attaining lactose tolerance in a majority of subjects. To investigate the mechanism, we examined the microbiome of human subjects before and after GOS feeding. The results show a significant shift in the microbiome of responsive individuals, including lactose-fermenting microbes in their stools. The high-purity prebiotic GOS resulted in adaptive shifts in the microbiome and correlated with improvement in clinical symptoms. </p><p class="first" id="d11100181e342">Directed modulation of the colonic bacteria to metabolize lactose effectively is a potentially useful approach to improve lactose digestion and tolerance. A randomized, double-blind, multisite placebo-controlled trial conducted in human subjects demonstrated that administration of a highly purified (&gt;95%) short-chain galactooligosaccharide (GOS), designated “RP-G28,” significantly improved clinical outcomes for lactose digestion and tolerance. In these individuals, stool samples were collected pretreatment (day 0), after GOS treatment (day 36), and 30 d after GOS feeding stopped and consumption of dairy products was encouraged (day 66). In this study, changes in the fecal microbiome were investigated using 16S rRNA amplicon pyrosequencing and high-throughput quantitative PCR. At day 36, bifidobacterial populations were increased in 27 of 30 of GOS subjects (90%), demonstrating a bifidogenic response in vivo. Relative abundance of lactose-fermenting <i>Bifidobacterium</i>, <i>Faecalibacterium</i>, and <i>Lactobacillus</i> were significantly increased in response to GOS. When dairy was introduced into the diet, lactose-fermenting <i>Roseburia</i> species increased from day 36 to day 66. The results indicated a definitive change in the fecal microbiome of lactose-intolerant individuals, increasing the abundance of lactose-metabolizing bacteria that were responsive to dietary adaptation to GOS. This change correlated with clinical outcomes of improved lactose tolerance. </p>