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  • Review Article
  • Published:

How glycan metabolism shapes the human gut microbiota

Nature Reviews Microbiology volume 10, pages 323–335 (2012)Cite this article

Subjects

Key Points

  • The degradation of complex carbohydrates (glycans and polysaccharides) is a major symbiotic function carried out by microorganisms that inhabit the human distal gut. These mutualistic species augment host nutrition by digesting glycans that the host cannot degrade, providing the host with usable metabolic products such as short-chain fatty acids.

  • Hundreds of different glycan structures enter the gut from dietary and endogenous sources. Endogenous sources include glycans from host mucus and shed host cells. The ∼103 species of microorganism that typically inhabit the human gut have evolved varying abilities to degrade these different substrates.

  • The type and abundance of glycans that are present in the gut change over long time periods. For example, human milk oligosaccharides are abundant before weaning, but they wane after weaning in favour of plant and animal tissue-based glycans.

  • The chemical identities of glycans that enter the gut also vary over short time periods, essentially from meal to meal. Variations in the foods we eat can affect the abundance of different microbial populations, leading to more profound population changes over time if dietary trends are consistent.

  • Different bacterial lineages that have evolved to be successful gut colonizers possess different strategies for glycan degradation. One such strategy is the starch utilization system (Sus)-like systems of members of the phylum Bacteroidetes, in which a series of outer-membrane and periplasmic proteins act together to bind, enzymatically degrade and import glycan products.

  • Other abundant bacterial lineages, such as the phyla Firmicutes and Actinobacteria, possess different glycan acquisition strategies that also involve glycan-degrading enzymes. In both of these Gram-positive lineages, the coupling of degradative enzymes to ABC (ATP-binding cassette) transporters seems to be a successful adaptation. Sequence-based analyses have also suggested that cellulosomes are present in some bacteria which inhabit the human gut.

  • Various host and dietary glycans are unlikely to be represented homogeneously throughout the gut. One example of this phenomenon is the presence of mucus glycans in a protective layer overlying the intestinal epithelium; this layer increases in thickness along the gut to the distal end.

  • Some species that have evolved to exploit mucus glycans as nutrients are present in higher numbers in the mucous layer than the lumen, suggesting that they are particularly important in the pathology of microbiota-associated diseases such as inflammatory bowel disease.

Abstract

Symbiotic microorganisms that reside in the human intestine are adept at foraging glycans and polysaccharides, including those in dietary plants (starch, hemicellulose and pectin), animal-derived cartilage and tissue (glycosaminoglycans and N-linked glycans), and host mucus (O-linked glycans). Fluctuations in the abundance of dietary and endogenous glycans, combined with the immense chemical variation among these molecules, create a dynamic and heterogeneous environment in which gut microorganisms proliferate. In this Review, we describe how glycans shape the composition of the gut microbiota over various periods of time, the mechanisms by which individual microorganisms degrade these glycans, and potential opportunities to intentionally influence this ecosystem for better health and nutrition.

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Figure 1: Sources and chemical variation of glycans in the gut.
Figure 2: Variations in functional complexity among starch utilization system (Sus)-like systems.
Figure 3: Glycan utilization along the length of the human gut and its potential health effects.
Figure 4: Glycan microhabitats and food chains in the gut.

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Acknowledgements

Work in E.C.M.'s laboratory is supported by the US National Institutes of Health (DK084214 and DK034933) and a Global Probiotics Council Young Investigator Grant. N.M.K. is supported by the University of Michigan (Ann Arbor, USA) Elizabeth M. Crosby faculty research grant. E.A.C. is supported by the University of Michigan Genetics Training Grant (GM07544).

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  1. Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, 48109, Michigan, USA

    Nicole M. Koropatkin, Elizabeth A. Cameron & Eric C. Martens

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CAZy

Glossary

Inflammatory bowel disease

A group of pathologies that are characterized by inflammation in the gut; the most notable examples are Crohn's disease and ulcerative colitis, which involve inflammation in the distal small intestine or the colon. These diseases are thought to stem from a congruence of host susceptibility factors (such as a genetic predisposition to uncontrolled inflammatory responses or reduced mucosal immunity) and stimulation by environmental or microbiological (bacterial and viral) triggers.

Glycans

Polymers of multiple simple sugars connected by covalent linkages. Glycans may be attached to other molecules such as lipids (forming glycolipids) and proteins (forming glycoproteins). Like nucleic acids, glycans have polarity: a linear molecule has one reducing end and one non-reducing end. Here, the term glycan is used synonymously with polysaccharide.

Short-chain fatty acids

Linear and branched fatty acids that contain six or fewer carbon atoms and are produced in addition to lactic and formic acids as end products of bacterial fermentation. These molecules are also referred to as volatile fatty acids. Examples include acetic, propionic and butyric acids.

Mucus

A viscous mixture consisting predominantly of mucin glycoproteins, which may be either attached to cell membranes or secreted from the cell in soluble form. Mucus frequently contains other secreted host compounds, such as secretory immunoglobulin A and antimicrobial peptides.

Glycosidic linkages

Chemical connections that occur between numbered carbon atoms in two sugar monomers, mediated by a shared oxygen atom. These bonds can be in the α- or β-conformation, and multiple linkages may be connected in linear or branched chains to construct more complex glycan structures.

Hemicellulose

A heterogeneous class of glycans that is found associated with cellulose in the matrix of plant cell walls. Unlike highly insoluble cellulose, hemicelluloses have more amorphous and flexible structures that help bind cellulose to pectin fibrils. The type and amount of hemicellulose in the plant cell wall is dependent on the botanical origin and includes molecules such as xylan, xyloglucan, galactomannan and glucomannan.

Pectin

A diverse class of polysaccharides composed of either a homopolymer of α1,4-linked galacturonic acid or a heteropolymer containing galacturonic acid and rhamnose (called rhamnogalacturon I). Each of these core pectin backbones can be extensively substituted with a range of modifications and glycan branches, including methyl and acetyl groups, monosaccharides such as xylose, and longer chains such as β-galactans and α-arabinans.

Prebiotics

Functional food components that selectively enhance the abundance or physiology of a subset of bacteria in the microbiota, with the goal of promoting the beneficial effects of these bacteria. Plant fibres that are resistant to human digestion are among the most common prebiotic therapies.

Germ-free mice

Mice that are raised in the complete absence of microbial colonization, usually following aseptic delivery by caesarian section and by housing the animals in sterile isolators that exclude access of environmental microorganisms. Other animal species such as rats, pigs and chickens have also been reared under germ-free conditions.

Food chains

Arrangements of multiple species in space and time that allow some members to feed either directly on others or on their by-products. Keystone members, which act first in a food chain, are particularly important because their absence also influences the status of the dependent species that are downstream in the food chain.

ABC transporters

(ATP-binding cassette transporters). A protein superfamily that is found in almost every form of life from bacteria to humans. These systems are typically composed of three main components: a solute-binding protein that binds ligands and dictates specificity, a membrane transporter through which the ligand passes, and an ATPase that provides the energy to drive ligand transport. Bacteria use ABC importers to take up nutrients such as iron, peptides or sugars, and ABC efflux transporters to pump toxic compounds out of the cell.

Cellulosome

An extracellular multienzyme complex that is formed in some Gram-positive bacteria and fungi. Cellulosomes bind and degrade plant cell wall polysaccharides that are otherwise resistant to degradation, including cellulose. Scaffoldin, the major non-enzymatic structural component, connects the enzymes via interactions between dockerin domains in the enzymes and cohesin modules in scaffoldin.

Human Microbiome Projects

Several ongoing efforts to sequence the microbial communities that are associated with various human body sites, including the gut. A major component of these projects is to sequence cultured 'reference' organisms. However, because many human-associated microorganisms have not yet been isolated in laboratory culture, a second approach is to directly sequence DNA extracted from microbial community samples (metagenomics).

Koch's postulates

Guidelines that are used to establish causality between a potential microbial pathogen and a disease, as published by Robert Koch in1890. The postulates state that a microorganism that causes a disease should be abundant in animals suffering from that disease, isolated from diseased specimens, able to be introduced into healthy animals to cause disease and able to be re-isolated from newly infected hosts.

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Koropatkin, N., Cameron, E. & Martens, E. How glycan metabolism shapes the human gut microbiota. Nat Rev Microbiol 10, 323–335 (2012). https://doi.org/10.1038/nrmicro2746

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