A novel gene cluster allows preferential utilization of fucosylated milk oligosaccharides in Bifidobacterium longum subsp. longum SC596

Abstract

The infant intestinal microbiota is often colonized by two subspecies of Bifidobacterium longum: subsp. infantis (B. infantis) and subsp. longum (B. longum). Competitive growth of B. infantis in the neonate intestine has been linked to the utilization of human milk oligosaccharides (HMO). However, little is known how B. longum consumes HMO. In this study, infant-borne B. longum strains exhibited varying HMO growth phenotypes. While all strains efficiently utilized lacto-N-tetraose, certain strains additionally metabolized fucosylated HMO. B. longum SC596 grew vigorously on HMO, and glycoprofiling revealed a preference for consumption of fucosylated HMO. Transcriptomes of SC596 during early-stage growth on HMO were more similar to growth on fucosyllactose, transiting later to a pattern similar to growth on neutral HMO. B. longum SC596 contains a novel gene cluster devoted to the utilization of fucosylated HMO, including genes for import of fucosylated molecules, fucose metabolism and two α-fucosidases. This cluster showed a modular induction during early growth on HMO and fucosyllactose. This work clarifies the genomic and physiological variation of infant-borne B. longum to HMO consumption, which resembles B. infantis. The capability to preferentially consume fucosylated HMO suggests a competitive advantage for these unique B. longum strains in the breast-fed infant gut.

Milk Glycans and Their Interaction with the Infant-Gut Microbiota

“…Unlike B. breve , most B. longum strains can grow moderately well on HMOs and well on LNT as a sole carbon source (Garrido et al 2016). In B. longum SC596, the LNB/GNB cluster was shown to be induced on the HMOs LNT and LNnT, which suggests the involvement of the LNB/GNB cluster in HMO utilization in this strain (Garrido et al 2016). From this strain, two galactosidases were found to be associated with HMO utilization.…”

“…From this strain, two galactosidases were found to be associated with HMO utilization. One of the galactosidases exhibited type I specificity, and the other had type II specificity (Garrido et al 2016). Furthermore, B. longum SC596 family 1 solute-binding proteins were induced on HMO and possessed binding affinity to various HMOs, including LNT, type I–like HMOs, and 2′-FL (Garrido et al 2016).…”

“…One of the galactosidases exhibited type I specificity, and the other had type II specificity (Garrido et al 2016). Furthermore, B. longum SC596 family 1 solute-binding proteins were induced on HMO and possessed binding affinity to various HMOs, including LNT, type I–like HMOs, and 2′-FL (Garrido et al 2016). Growth on 2′-FL and 3-FL as the sole carbon sources is strain dependent in B. longum (Garrido et al 2016) .…”

Feeding the microbiota: transducer of nutrient signals for the host

“…Furthermore, it has become apparent that the genomes of these anaerobic microbes encode a broad spectrum of glycan-degrading enzymes, some of which represent species-specific glycosyl hydrolases that metabolise particular HMOs, such as fucosyl-lactose, sialyl-lactose and lacto-N-tetraose 44–47 . Molecular analys es show that Bifidobacterium longum subsp infantis and Bifidobacterium bifidum are endowed with the widest range of HMO-degrading abilities, whereas other infant-associated bifidobacteria such as Bifidobacterium breve and B. longum  subsp longum are much more limited in this regard 48. However, it has been shown for B. breve that this species cross feeds on the HMO-derived carbohydrates released by the extracellular enzymes of B. bifidum indicating that certain bifidobacterial species support each other, whereas others are more ‘egocentric’ in nature as they internalise the HMOs prior to hydrolysis 49.…”

Non-digestible carbohydrates in infant formula as substitution for human milk oligosaccharide functions: Effects on microbiota and gut maturation

“…These bacteria have the ability to utilize HMOs, depending on their equipment with dedicated glycoside hydrolases, transporters and other molecules contributing to degradation (Goh and Klaenhammer 2015). As certain bacteria such as Bifidobacteria and Lactobacilli specifically express sialidases to cleave Sia and fucosidases to cleave Fuc, it is believed that these species co-evolved with HMOs (Garrido et al 2016;LoCascio et al 2007;Sela et al 2012;Ward et al 2006).…”