A Continuous Battle for Host-Derived Glycans Between a Mucus Specialist and a Glycan Generalist in vitro and in vivo

Ioannis Kostopoulos; Steven Aalvink; Petia Kovatcheva-Datchary; Bart Nijsse; Fredrik Bäckhed; Jan Knol; Willem M de Vos; Clara Belzer

doi:10.3389/fmicb.2021.632454

A Continuous Battle for Host-Derived Glycans Between a Mucus Specialist and a Glycan Generalist in vitro and in vivo

Front Microbiol. 2021 Jun 24:12:632454. doi: 10.3389/fmicb.2021.632454. eCollection 2021.

Authors

Ioannis Kostopoulos¹, Steven Aalvink¹, Petia Kovatcheva-Datchary², Bart Nijsse³, Fredrik Bäckhed², Jan Knol^{1

4}, Willem M de Vos^{1

5}, Clara Belzer¹

Affiliations

¹ Laboratory of Microbiology, Wageningen University, Wageningen, Netherlands.
² Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.
³ Laboratory of Systems and Synthetic Biology, Wageningen University, Wageningen, Netherlands.
⁴ Danone Nutricia Research, Utrecht, Netherlands.
⁵ Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Abstract

The human gastrointestinal tract is colonized by a diverse microbial community, which plays a crucial role in human health. In the gut, a protective mucus layer that consists of glycan structures separates the bacteria from the host epithelial cells. These host-derived glycans are utilized by bacteria that have adapted to this specific compound in the gastrointestinal tract. Our study investigated the close interaction between two distinct gut microbiota members known to use mucus glycans, the generalist Bacteroides thetaiotaomicron and the specialist Akkermansia muciniphila in vitro and in vivo. The in vitro study, in which mucin was the only nutrient source, indicated that B. thetaiotaomicron significantly upregulated genes coding for Glycoside Hydrolases (GHs) and mucin degradation activity when cultured in the presence of A. muciniphila. Furthermore, B. thetaiotaomicron significantly upregulated the expression of a gene encoding for membrane attack complex/perforin (MACPF) domain in co-culture. The transcriptome analysis also indicated that A. muciniphila was less affected by the environmental changes and was able to sustain its abundance in the presence of B. thetaiotaomicron while increasing the expression of LPS core biosynthesis activity encoding genes (O-antigen ligase, Lipid A and Glycosyl transferases) as well as ABC transporters. Using germ-free mice colonized with B. thetaiotaomicron and/or A. muciniphila, we observed a more general glycan degrading profile in B. thetaiotaomicron while the expression profile of A. muciniphila was not significantly affected when colonizing together, indicating that two different nutritional niches were established in mice gut. Thus, our results indicate that a mucin degrading generalist adapts to its changing environment, depending on available carbohydrates while a mucin degrading specialist adapts by coping with competing microorganism through upregulation of defense related genes.

Keywords: Akkermansia muciniphila; Bacteroides thetaiotaomicron; antimicrobial proteins; germ free mice; glycosyl hydrolases; mucin glycans.