Bifidogenic Effect of Human Milk Oligosaccharides on Pediatric IBD Fecal Microbiota

The prevalence of pediatric inflammatory bowel disease (pIBD) has been increasing over the last two decades. Yet, treatment strategies are still limited, in part due to the multifactorial nature of the disease and the complex interplay between genetic, environmental, dietary, immune, and gut microbial factors in its etiology. With their direct and indirect anti-inflammatory properties, human milk oligosaccharides (HMOs) are a promising treatment and management strategy for IBD. However, to date there are no insights into how HMOs may affect pIBD microbiota. Here, we compared the effects of 2'fucosyllactose (2'FL), difucosyllactose (DFL), 3'sialyllactose (3'SL), and blends thereof with fructooligosaccharide (FOS) on microbiota functionality (short- and branched-chain fatty acids, pH, and gas production) and composition (quantitative shallow shotgun sequencing) using fecal material from eight different pediatric Crohn's disease patients inoculated in the SIFR^® technology. In general, all HMO treatments significantly increased total short-chain fatty acid production when compared with FOS, despite equal gas production. We found that 2'FL, either alone or in combination with DFL and 3'SL, exhibited a strong acetogenic and propiogenic effect, and 3'SL an acetogenic effect that surpassed the effects observed with FOS. No differences in overall community diversity between HMO- and FOS-treated pIBD microbiota were observed. There was, however, a stronger bifidogenic effect of 2'FL, 3'SL, 2'FL/DFL, and 2'FL/DFL + 3'SL when compared with FOS. In general, 3'SL and HMO blends enriched a broader species profile, including taxa with potentially anti-inflammatory properties, such as <i>Faecalibacterium prausnitzii</i> and <i>Blautia</i> species. This study suggests HMOs as a promising strategy to beneficially alter the gut microbial profile in pIBD.