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

Abstract

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 (>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 Bifidobacterium, Faecalibacterium, and Lactobacillus were significantly increased in response to GOS. When dairy was introduced into the diet, lactosefermenting Roseburia 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 lactosemetabolizing bacteria that were responsive to dietary adaptation to GOS. This change correlated with clinical outcomes of improved lactose tolerance.A limited ability to digest lactose occurs when the intestinal lactase enzyme is reduced in the brush border of the small bowel mucosa. Consumption of dairy foods by lactose-intolerant individuals may result in clinical symptoms including abdominal pain, diarrhea, bloating, flatulence, and abdominal cramping. In these cases, lactose travels through the gastrointestinal tract and is fermented in the colon, producing acetate, carbon dioxide, hydrogen gas, and methane by gas-producing microbes. Approximately 75% of the global human population are lactose maladsorbers (1, 2). In the United States, it is estimated that up to 80 million Americans are at risk for lactose intolerance.Efforts to address lactose intolerance include avoidance of dairy foods, reduction in the lactose content of milk through treatment with microbial lactases, and the use of lactase enzymes to process milk before dairy consumption (3). Savaiano et al. conducted a randomized, double-blind, parallel-group, placebocontrolled study at two sites in the United States (4). A high purity (>95%) galactooligosaccharide (GOS/RP-G28) or a placebo (Sweetose; Tate & Lyle Ingredients) was administered in increasing doses to 62 lactose-intolerant subjects for 36 d. Subjects refrained from consuming lactose during the GOS treatment period. After GOS treatment, subjects reintroduced dairy products into their diets for an additional 30 d and then were challenged for lactose digestion and were evaluated for symptoms improvement via a Likert scale. Subjects consuming GOS trended toward improvement in overall symptoms after 36 d of ...

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