Bacterial Processing of Glycans
Dietary carbohydrates are essential for the gut
microbiota201. Many gut commensals have
carbohydrate-active enzymes (CAZymes), which facilitate the processing
of a range of glycans (Fig. 1G)202,203. CAZymes vary
among individuals depending on factors such as age and
geography204. Differential glycan preferences are
exhibited by the various microbes found in the gut, resulting in diverse
metabolism203. For example, Bacteroidetes
thetaitaomicron, B. fragilis, and Ruminococcus torques can break
down molecules such as mucin163,205,206. B .thetaitaomicron can metabolize L-fucose as an energy source and
induce host FUTs to increase mucosal fucosylation, creating a beneficial
environment for itself62,207. Additionally, B .thetaitaomicron can help increase sialic acid-carrying glycan
expression208. Bacterial exoglycosidases release
monosaccharide residues from mucin for the bacteria to use as an energy
source under homeostatic conditions (Fig. 1G)209.
On the other hand, Bifidobacteria can break down human milk
oligosaccharides (HMOs) to aid in their digestion, a process important
for infants who lack the enzymatic capability to process
HMOs210,211. Exposure to HMOs in breast milk in
infancy helps Bifidobacteria to colonize the gut and help the
host develop an immune tolerance towards commensal bacteria since HMOs
act as a carbon source for the gut microbiota and
host212. HMO metabolism is a virulence-suppressing
process and is required to prevent the adhesion of pathogens to the
intestinal epithelia as HMOs resemble epithelial surface glycans,
allowing them to act as decoy receptors for bacteria (like E.
coli and Vibrio cholerae ), and hence, preventing the attachment
of the bacteria to the gut211,213. HMOs assert their
anti-inflammatory effects by regulating interleukin production and
lymphocyte activation. Additionally, sialylated HMOs can help maintain a
Th1/Th2 balance214,215.
The process of dietary fiber fermentation by the gut microbiota starts
with the breakdown of complex glycans into simpler sugars, which are
then fermented by the intestinal anaerobic microorganisms (Fig. 1G).
This fermentation process causes the production of short-chain fatty
acids (SCFAs), which are absorbed from the colon to be used in numerous
metabolic processes216,217. One such SCFA is butyrate.
It is the preferred energy source of colonocytes, and it facilitates the
maturation of the colonic mucus barrier218,219.
However, deviations from its physiological concentrations may cause
colon cancer220. Impaired butyrate oxidation is also
evident in patients with ulcerative colitis (Fig.
2G)221. A low-fiber diet has been associated with
reduced beneficial gut bacteria and increased risk for
IBD222. Comparably, a high-fiber diet can promote an
increase in the Prevotella genus, which has reduced colonization in
individuals with low-fiber diets223,224. A high-fiber
diet stimulates an increase in glycan metabolism by the gut bacteria and
helps up-regulate SCFA production, thereby reducing
inflammation225.
Due to its high glycan content, the mucus layer serves as a nutrient
source for the inhabitant bacteria202. Mucin glycan
utilization gives bacteria a consistent nutrient supply and helps the
bacteria colonize the mucus layer226. In the hGM, due
to their diverse CAZymes, Bacteroidetes are general glycan degraders
that can use both dietary and host glycans (Fig.
1G)227. Bifidobacteria and Firmicutes genera show
similar glycan degradation patterns since they both use carbohydrates
with low levels of polymerization227.Akkermansia muciniphila is another important bacterial species
that degrades mucus glycans into acetate to support butyrate-producing
bacteria228,229. Conversely, A.muciniphila can show mucus thinning effects in low-fiber diets
and dysbiosis230. Mucolytic bacteria can also generate
SCFAs through fermentation. These SCFAs can be utilized by non-mucolytic
bacteria or used by the host to recover the energy that was used in the
mucin synthesis and secretion231. MUC2 expression can
also be increased by SCFAs232.
Mucin degradation by bacteria is an essential process in establishing a
stable microbiota168. The symbiotic relationship
between the host and the microbiota relies on the microbes’ capabilities
of host glycan digestion and the host’s ability to secrete mucin glycans
for microbial stimuli17. If the dietary
polysaccharides were to be depleted from the host’s diet, this would
result in a significant shift to gut bacterial consumption of host
mucus8. If the host has a low-fiber diet, this results
in decreased microbial diversity and a shift in microbial composition to
sole reliance on host mucus8,149. Increased reliance
on host mucus eventually wears down the mucus barrier and causes an
inevitable breach of the mucus layer, as observed in ulcerative colitis
patients149. This data also supports the finding that
the low fiber content in the Western diet leads to increased IBD
prevalence149.