Cross-feeding interactions of gut symbionts driven by human milk oligosaccharidesand mucins

Abstract

Chapter 4Microbial metabolic networks at the mucus layer lead to dietindependent butyrate and vitamin B12 production by intestinal symbionts 71 Chapter 5Deciphering trophic interaction between Akkermansia muciniphila and the butyrogenic gut commensal Anaerostipes caccae using a metatranscriptomic approach 97 Chapter 6General discussion 123 Chapter 7 Thesis summary & Nederlandse samenvatting 143 Appendices References 153Co-author affiliations 179Acknowledgements 183About the author 184List of publications 185 VLAG training activities 186Chapter 1 General introduction and thesis outlineChapter 1 2 General introductionHumans can be considered holobionts, consisting of cells from the host and an even larger number of microorganisms (Postler and Ghosh 2017). The majority of microbes are residing in the gut (Sender et al 2016). The human gut microbiota is a complex ecosystem consisting of bacteria, archaea, microeukaryotes and viruses (Clemente et al 2012). Over 2000 species-level phylotypes (prokaryotes including bacteria and archaea) have been detected for the gut microbiota, with each individual estimated to host at least 160 species (Qin et al 2010, Zoetendal et al 2008. The gut microbiota may impact the well-being of human and susceptibility for diseases by interacting with our metabolic, immune and neurological system (Honda and Littman 2016, Koh et al 2016, Rogers et al 2016. Furthermore, the gut microbiota contributes to a variety of metabolic functions and can be seen as an essential part of our digestive system (El Kaoutari et al 2013). Bacterial symbionts allow the human hosts to utilise inaccessible nutrients by converting complex substrates to short chain fatty acid (SCFA) and vitamins (Fisher et al 2017). Bacterial-derived SCFAs are estimated to contribute about 10% of our daily caloric requirement (Bergman 1990). While all SCFAs are vital for maintaining gut homeostasis, butyrate is of particular interest because it has been attributed to a range of health-promoting functions. Butyrate is the primary energy source for colonic epithelial cells and is associated with the enhancement of colonic barrier function, increase of satiety, pain relief, anti-inflammatory responses, and protection against colorectal cancer (Banasiewicz et al 2013, Bolognini et al 2016, Donohoe et al 2011, Furusawa et al 2013, Goncalves and Martel 2013.Considering the physiological benefits of butyrate to human health, this thesis investigates the microbial interaction of gut symbionts that support butyrate production driven primarily by the host produced glycans in human milk and mucus. Glycans are compounds consisting of an array of glycosidically linked monosaccharides (monosaccharides and disaccharides are collectively termed sugars) such as human milk oligosaccharides (HMOS) and mucins (Varki and Kornfeld 2017). HMOS present in mother milk are the major compositional and functional driver of the infant gut microbiota (Backhed et al 2015). Mucin glycans covering the intestinal lining create a stable niche for bacterial coloni...

Microbial Glycoside Hydrolases in the First Year of Life: An Analysis Review on Their Presence and Importance in Infant Gut

“…The utilization of FOS requires mainly enzymes that cleave the Fuc moieties from the oligosaccharides and belong to the GH13, GH32, and GH68 families. However, agreeing to previous exploratory attempts (Chia, 2018) there were no available data for characterized GH68 enzymes in known infant gut bacteria.…”

“…infantis (Karav et al, 2018), is performed by, for example, the increasing Bacteroides thetaiotaomicron, A. muciniphila (Bergström et al, 2014;Bäckhed et al, 2015;Differding et al, 2020) and the pre-established B. bifidum (Tsai et al, 1991;Derrien et al, 2004;Ruas-Madiedo et al, 2008). These O-glycans (Supplementary Figure 2) are targeted by some GHs that are common with the previously mentioned HMO-related CAZymes, namely fucosidases (GH29, GH95), sialidases (GH33), sulfatases, and β-hexosaminidases (GH20) (Chia, 2018;Chia et al, 2020;Kostopoulos et al, 2020). Absence of indigestible carbohydrates in gnotobiotic mice shifted the intestinal bacteria to transcriptional increase of CAZymes of mucin degradation (Desai et al, 2016), possible evidence of the protective role of prebiotics toward the integrity of the mucosal barrier.…”

Daily skin-to-skin contact alters microbiota development in healthy full-term infants

“…Anaerobutyricum soehngenii can produce butyrate by utilizing the byproducts of other early colonizers that metabolize human milk oligosaccharides. 83 , 84 It has been positively associated with infant colic 85 and is under investigation for its benefits in relation to glucose metabolism. 86 …”