Effects of Human Milk Oligosaccharides on the Adult Gut Microbiota and Barrier Function

Abstract

Human milk oligosaccharides (HMOs) shape the gut microbiota in infants by selectively stimulating the growth of bifidobacteria. Here, we investigated the impact of HMOs on adult gut microbiota and gut barrier function using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®), Caco2 cell lines, and human intestinal gut organoid-on-chips. We showed that fermentation of 2’-O-fucosyllactose (2’FL), lacto-N-neotetraose (LNnT), and combinations thereof (MIX) led to an increase of bifidobacteria, accompanied by an increase of short chain fatty acid (SCFA), in particular butyrate with 2’FL. A significant reduction in paracellular permeability of FITC-dextran probe was observed using Caco2 cell monolayers with fermented 2’FL and MIX, which was accompanied by an increase in claudin-8 gene expression as shown by qPCR, and a reduction in IL-6 as determined by multiplex ELISA. Using gut-on-chips generated from human organoids derived from proximal, transverse, and distal colon biopsies (Colon Intestine Chips), we showed that claudin-5 was significantly upregulated across all three gut-on-chips following treatment with fermented 2’FL under microfluidic conditions. Taken together, these data show that, in addition to their bifidogenic activity, HMOs have the capacity to modulate immune function and the gut barrier, supporting the potential of HMOs to provide health benefits in adults.

Impact of 2′-Fucosyllactose on Gut Microbiota Composition in Adults with Chronic Gastrointestinal Conditions: Batch Culture Fermentation Model and Pilot Clinical Trial Findings

“…Using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME ® ), Šuligoj et al [ 59 ] recently reported that fermentation of 2′-FL resulted in a simultaneous increase in Bifidobacterium and SCFAs including butyrate in particular. In our in vitro experiments, fermentation of stool samples with 2′-FL also resulted in a simultaneous increase in Bifidobacterium and SCFAs including butyrate.…”

Human Milk Microbiota and Oligosaccharides: A Glimpse into Benefits, Diversity, and Correlations

“…HMOs, through metabolism into short chain fatty acids and cross feeding with butyrate-producing bacteria, induce butyrate production in the colon. Butyrate is an essential metabolite, as it forms the preferable energy source for colon epithelial cells, contributes to the preservation of the gut barrier, and displays immunomodulatory effects [ 224 ]. Therefore, HMOs support barrier function through promotion of the formation of fermentation products, especially by Bifidobacterium [ 225 ].…”

“…Such condition includes ageing, irritable bowel syndrome, or inflammatory bowel disease. However, the exact mechanism of these effects remains to be largely explored [ 224 ].…”

“…Although attempts to synthesize HMOs represent an initial phase in tapering the compositional gap between human milk and infant formula, it is unclear whether one or two HMO molecules will be capable of inducing the complex actions exerted by the rich blend of HMOs that breastfed infants ingest in human milk. Interestingly, 2′-FL, LNnT, and combinations of both used in a simulated ecosystem of adult human intestine were shown to increase bifidobacterial levels and to decrease levels of IL-6 and cellular permeability [ 224 ]. Still, a low diversity of HMOs in breast milk was associated with necrotizing enterocolitis in infants fed exclusively with breast milk [ 235 ].…”

“…Plus, the use of human milk-based fortifiers having a full spectrum of HMOs, similar to that in breast milk, is quite tempting to nourish infants and support their gut development and maturity and warrants further investigation. Moreover, the capacity of HMOs to modulate the immune function and to reinforce the gut barrier might support their ability to afford health paybacks in adults, rather than in infants only [ 224 ]. Despite that the focus on HMO supplementation to date has been on infants, the transfer of HMOs to adults as well seems on the rise, and commercialization of HMOs is slowly, but surely, coming to make a case for HMO adult supplementation.…”