Review Article | Published:

How glycan metabolism shapes the human gut microbiota

Nature Reviews Microbiology volume 10, pages 323335 (2012) | Download Citation

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.

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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    & The gut microbiota shapes intestinal immune responses during health and disease. Nature Rev. Immunol. 9, 313–323 (2009).

  2. 2.

    , , , & Polysaccharide utilization by gut bacteria: potential for new insights from genomic analysis. Nature Rev. Microbiol. 6, 121–131 (2008).

  3. 3.

    , & Current concepts of the intestinal microbiota and the pathogenesis of infection. Curr. Infect. Dis. Rep. 13, 28–34 (2011).

  4. 4.

    & Commensal bacteria, traditional and opportunistic pathogens, dysbiosis and bacterial killing in inflammatory bowel diseases. Curr. Opin. Infect. Dis. 22, 292–301 (2009).

  5. 5.

    et al. Products of the colonic microbiota mediate the effects of diet on colon cancer risk. J. Nutr. 139, 2044–2048 (2009).

  6. 6.

    , , & Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent Clostridium difficile-associated diarrhea. J. Clin. Gastroenterol. 44, 354–360 (2010).

  7. 7.

    , , & Microbial ecology: human gut microbes associated with obesity. Nature 444, 1022–1023 (2006).

  8. 8.

    , & Host genetic susceptibility, dysbiosis, and viral triggers in inflammatory bowel disease. Curr. Opin. Gastroenterol. 27, 321–327 (2011).

  9. 9.

    et al. Enterobacteriaceae act in concert with the gut microbiota to induce spontaneous and maternally transmitted colitis. Cell Host Microbe 8, 292–300 (2010).

  10. 10.

    et al. Commensal bacteroides species induce colitis in host-genotype-specific fashion in a mouse model of inflammatory bowel disease. Cell Host Microbe 9, 390–403 (2011).

  11. 11.

    et al. Diversity of the human intestinal microbial flora. Science 308, 1635–1638 (2005).

  12. 12.

    et al. Organismal, genetic, and transcriptional variation in the deeply sequenced gut microbiomes of identical twins. Proc. Natl Acad. Sci. USA 107, 7503–7508 (2010).

  13. 13.

    et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464, 59–65 (2010).

  14. 14.

    et al. Enterotypes of the human gut microbiome. Nature 473, 174–180 (2011). A metagenomics-based analysis of a total of 272 new and published human faecal microbiomes, revealing the existence of just three dominant enterotypes.

  15. 15.

    et al. Moving pictures of the human microbiome. Genome Biol. 12, R50 (2011). The first long-term study of the dynamics of the human faecal microbiome, with a daily time point analysis.

  16. 16.

    The contribution of the large intestine to energy supplies in man. Am. J. Clin. Nutr. 39, 338–342 (1984).

  17. 17.

    , , & Fermentation of mucin and plant polysaccharides by strains of Bacteroides from the human colon. Appl. Environ. Microbiol. 33, 319–322 (1977).

  18. 18.

    , , & Fermentation of mucins and plant polysaccharides by anaerobic bacteria from the human colon. Appl. Environ. Microbiol. 34, 529–533 (1977).

  19. 19.

    et al. Bacteroides in the infant gut consume milk oligosaccharides via mucus-utilization pathways. Cell Host Microbe 10, 507–514 (2011).

  20. 20.

    Pectin structure and biosynthesis. Curr. Opin. Plant Biol. 11, 266–277 (2008).

  21. 21.

    , , & Cell wall polysaccharide interactions in maize bran. Carbohydr. Polym. 26, 279–287 (1995).

  22. 22.

    , , & A complex, but uniform O-glycosylation of the human MUC2 mucin from colonic biopsies analyzed by nanoLC/MSn. Glycobiology 19, 756–766 (2009).

  23. 23.

    et al. Review article: the role of butyrate on colonic function. Aliment. Pharmacol. Ther. 27, 104–119 (2008).

  24. 24.

    & Metabolic and intestinal effects of short-chain fatty acids. JPEN. J. Parenter. Enteral Nutr. 14, S181–S185 (1990).

  25. 25.

    , , , & Acetate utilization and butyryl coenzyme A (CoA):acetate-CoA transferase in butyrate-producing bacteria from the human large intestine. Appl. Environ. Microbiol. 68, 5186–5190 (2002).

  26. 26.

    et al. Contribution of acetate to butyrate formation by human faecal bacteria. Br. J. Nutr. 91, 915–923 (2004).

  27. 27.

    et al. Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature 469, 543–547 (2011).

  28. 28.

    , , , & Development of the human infant intestinal microbiota. PLoS Biol. 5, e177 (2007).

  29. 29.

    et al. Succession of microbial consortia in the developing infant gut microbiome. Proc. Natl Acad. Sci. USA 108 (Suppl. 1), 4578–4585 (2010). A study of microbiota formation in a single human child over the first 3 years of life, using 16S rRNA genes and metagenomic approaches to correlate changes in the microbiota with life events such as diet shifts, illness and antibiotics.

  30. 30.

    , , , & Oligosaccharides in human milk: structural, functional, and metabolic aspects. Annu. Rev. Nutr. 20, 699–722 (2000).

  31. 31.

    et al. A strategy for annotating the human milk glycome. J. Agric. Food Chem. 54, 7471–7480 (2006).

  32. 32.

    et al. Milk sialyllactose influences colitis in mice through selective intestinal bacterial colonization. J. Exp. Med. 207, 2843–2854 (2010).

  33. 33.

    , , , & Survival of human milk oligosaccharides in the intestine of infants. Adv. Exp. Med. Biol. 501, 315–323 (2001).

  34. 34.

    , , & Human milk oligosaccharides: evolution, structures and bioselectivity as substrates for intestinal bacteria. Nestle Nutr. Workshop Ser. Pediatr. Program 62, 205–218; discussion 218–222 (2008).

  35. 35.

    , , & Human milk oligosaccharides are minimally digested in vitro. J. Nutr. 130, 3014–3020 (2000).

  36. 36.

    , , & Molecular monitoring of succession of bacterial communities in human neonates. Appl. Environ. Microbiol. 68, 219–226 (2002).

  37. 37.

    Bifidobacterial utilization of human milk oligosaccharides. Int. J. Food Microbiol. 149, 58–64 (2011).

  38. 38.

    et al. Cooperation of β-galactosidase and β-N-acetylhexosaminidase from bifidobacteria in assimilation of human milk oligosaccharides with type 2 structure. Glycobiology 20, 1402–1409 (2010).

  39. 39.

    , , , & Broad conservation of milk utilization genes in Bifidobacterium longum subsp. infantis as revealed by comparative genomic hybridization. Appl. Environ. Microbiol. 76, 7373–7381 (2010).

  40. 40.

    et al. Genome analysis of Bifidobacterium bifidum PRL2010 reveals metabolic pathways for host-derived glycan foraging. Proc. Natl Acad. Sci. USA 107, 19514–19519 (2010).

  41. 41.

    , , , & Oligosaccharide binding proteins from Bifidobacterium longum subsp. infantis reveal a preference for host glycans. PLoS ONE 6, e17315 (2011).

  42. 42.

    et al. In vitro evaluation of gastrointestinal survival of Lactobacillus amylovorus DSM 16698 alone and combined with galactooligosaccharides, milk and/or Bifidobacterium animalis subsp. lactis Bb-12. Int. J. Food Microbiol. 149, 152–158 (2011).

  43. 43.

    , & Utilization of natural fucosylated oligosaccharides by three novel α-L-fucosidases from a probiotic Lactobacillus casei strain. Appl. Environ. Microbiol. 77, 703–705 (2011).

  44. 44.

    & Lactic acid bacteria fermentation of human milk oligosaccharide components, human milk oligosaccharides and galactooligosaccharides. FEMS Microbiol. Lett. 315, 141–148 (2011).

  45. 45.

    et al. Oligosaccharides in human milk during different phases of lactation. Acta Paediatr. Suppl. 88, 89–94 (1999).

  46. 46.

    , & Development of bacterial and bifidobacterial communities in feces of newborn babies. Anaerobe 9, 219–229 (2003).

  47. 47.

    et al. Determinants of the human infant intestinal microbiota after the introduction of first complementary foods in infant samples from five European centres. Microbiology 157, 1385–1392 (2011).

  48. 48.

    et al. Analysis of intestinal flora development in breast-fed and formula-fed infants by using molecular identification and detection methods. J. Pediatr. Gastroenterol. Nutr. 30, 61–67 (2000).

  49. 49.

    et al. Comparative metagenomics revealed commonly enriched gene sets in human gut microbiomes. DNA Res. 14, 169–181 (2007).

  50. 50.

    et al. The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age. BMC Microbiol. 9, 123 (2009).

  51. 51.

    et al. Glycan foraging in vivo by an intestine-adapted bacterial symbiont. Science 307, 1955–1959 (2005). The first in vivo transcriptomics-based study of a human gut symbiont (B. thetaiotaomicron) in the intestines of gnotobiotic mice consuming diets with varying glycan content.

  52. 52.

    , & Functional genomic and metabolic studies of the adaptations of a prominent adult human gut symbiont, Bacteroides thetaiotaomicron, to the suckling period. J. Biol. Chem. 281, 36269–36279 (2006).

  53. 53.

    , & Mucosal glycan foraging enhances fitness and transmission of a saccharolytic human gut bacterial symbiont. Cell Host Microbe 4, 447–457 (2008). A study that uses transcriptional profiling of in vitro-grown cultures to identify B. thetaiotaomicron genes that are involved in the degradation of host glycans. This study demonstrates a link between foraging for host glycans and intergenerational transmission of microbiota members.

  54. 54.

    et al. Bacterial community variation in human body habitats across space and time. Science 326, 1694–1697 (2009).

  55. 55.

    et al. Variations of bacterial populations in human feces measured by fluorescent in situ hybridization with group-specific 16S rRNA-targeted oligonucleotide probes. Appl. Environ. Microbiol. 64, 3336–3345 (1998).

  56. 56.

    , & Temperature gradient gel electrophoresis analysis of 16S rRNA from human fecal samples reveals stable and host-specific communities of active bacteria. Appl. Environ. Microbiol. 64, 3854–3859 (1998).

  57. 57.

    et al. Obesity alters gut microbial ecology. Proc. Natl Acad. Sci. USA 102, 11070–11075 (2005).

  58. 58.

    et al. Improvement of the representation of bifidobacteria in fecal microbiota metagenomic libraries by application of the cpn60 universal primer cocktail. Appl. Environ. Microbiol. 76, 4550–4552 (2010).

  59. 59.

    et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc. Natl Acad. Sci. USA 107, 14691–14696 (2010). An investigation that analyses the composition of the microbiota in two populations of children (one in Africa and the other in Europe) that consume different diets.

  60. 60.

    et al. Towards the human intestinal microbiota phylogenetic core. Environ. Microbiol. 11, 2574–2584 (2009).

  61. 61.

    & The bifidogenic effect of inulin and oligofructose and its consequences for gut health. Eur. J. Clin. Nutr. 63, 1277–1289 (2009).

  62. 62.

    et al. Specificity of polysaccharide use in intestinal Bacteroides species determines diet-induced microbiota alterations. Cell 141, 1241–1252 (2010). A mechanistic study of fructan utilization by multiple Bacteroides spp. from the human gut microbiota, revealing that a single gene cluster can be evolutionarily altered between species to switch glycan substrate specificity.

  63. 63.

    et al. Butyrate inhibits inflammatory responses through NFκB inhibition: implications for Crohn's disease. Gut 47, 397–403 (2000).

  64. 64.

    et al. Cytokine-activated degradation of inhibitory κB protein α is inhibited by the short-chain fatty acid butyrate. Int. J. Colorectal Dis. 16, 195–201 (2001).

  65. 65.

    et al. Butyrate modulates oxidative stress in the colonic mucosa of healthy humans. Clin. Nutr. 28, 88–93 (2009).

  66. 66.

    , , , & The microbiology of butyrate formation in the human colon. FEMS Microbiol. Lett. 217, 133–139 (2002).

  67. 67.

    , , & Apoptosis cascade proteins are regulated in vivo by high intracolonic butyrate concentration: correlation with colon cancer inhibition. Oncol. Res. 12, 83–95 (2000).

  68. 68.

    , & Butyrate production from dietary fibre and protection against large bowel cancer in a rat model. Gut 34, 386–391 (1993).

  69. 69.

    , , , & Cell kinetics and gene expression changes in colorectal cancer patients given resistant starch: a randomised controlled trial. Gut 58, 413–420 (2009).

  70. 70.

    , , , & Effects of high-amylose maize starch and butyrylated high-amylose maize starch on azoxymethane-induced intestinal cancer in rats. Carcinogenesis 29, 2190–2194 (2008).

  71. 71.

    et al. Butyric acid-producing anaerobic bacteria as a novel probiotic treatment approach for inflammatory bowel disease. J. Med. Microbiol. 59, 141–143 (2010).

  72. 72.

    & How does oxygen inhibit central metabolism in the obligate anaerobe Bacteroides thetaiotaomicron. Mol. Microbiol. 39, 1562–1571 (2001).

  73. 73.

    et al. Butyricimonas synergistica gen. nov., sp. nov. and Butyricimonas virosa sp. nov., butyric acid-producing bacteria in the family 'Porphyromonadaceae' isolated from rat faeces. Int. J. Syst. Evol. Microbiol. 59, 1748–1753 (2009).

  74. 74.

    , , , & Resistant starches types 2 and 4 have differential effects on the composition of the fecal microbiota in human subjects. PLoS ONE 5, e15046 (2010).

  75. 75.

    et al. Dominant and diet-responsive groups of bacteria within the human colonic microbiota. ISME J. 5, 220–230 (2011). A human volunteer study that tracks the changes in the microbiota following a shift to a low-carbohydrate diet, then to an RS-containing diet and finally to a diet that is rich in non-starch polysaccharides.

  76. 76.

    , , , & Selective colonization of insoluble substrates by human faecal bacteria. Environ. Microbiol. 9, 667–679 (2007).

  77. 77.

    & Composition and metabolic activities of bacterial biofilms colonizing food residues in the human gut. Appl. Environ. Microbiol. 72, 6204–6211 (2006).

  78. 78.

    et al. The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci. Transl. Med. 1, 6ra14 (2009). An investigation that uses culture-independent methods to monitor alterations in the microbiota of humanized mice in response to rapid diet shift.

  79. 79.

    , , & Predicting a human gut microbiota's response to diet in gnotobiotic mice. Science 333, 101–104 (2011).

  80. 80.

    et al. Extensive personal human gut microbiota culture collections characterized and manipulated in gnotobiotic mice. Proc. Natl Acad. Sci. USA 108, 6252–6257 (2011).

  81. 81.

    et al. Linking long-term dietary patterns with gut microbial enterotypes. Science 334, 105–108 (2011).

  82. 82.

    et al. Characterizing a model human gut microbiota composed of members of its two dominant bacterial phyla. Proc. Natl Acad. Sci. USA 106, 5859–5864 (2009).

  83. 83.

    & Contribution of a neopullulanase, a pullulanase, and an α-glucosidase to growth of Bacteroides thetaiotaomicron on starch. J. Bacteriol. 178, 7173–7179 (1996).

  84. 84.

    & Biochemical analysis of interactions between outer membrane proteins that contribute to starch utilization by Bacteroides thetaiotaomicron. J. Bacteriol. 183, 7224–7230 (2001).

  85. 85.

    et al. Evolution of symbiotic bacteria in the distal human intestine. PLoS Biol. 5, e156 (2007).

  86. 86.

    , , & Complex glycan catabolism by the human gut microbiota: the Bacteroidetes Sus-like paradigm. J. Biol. Chem. 284, 24673–24677 (2009).

  87. 87.

    , , & Location and characterization of genes involved in binding of starch to the surface of Bacteroides thetaiotaomicron. J. Bacteriol. 174, 5609–5616 (1992).

  88. 88.

    et al. A genomic view of the human-Bacteroides thetaiotaomicron symbiosis. Science 299, 2074–2076 (2003).

  89. 89.

    et al. Recognition and degradation of plant cell wall polysaccharides by two human gut symbionts. PLoS Biol. 9, e1001221 (2011). The first transcriptomic and genetic study to link specific genes in Bacteroides spp. from the human gut microbiota with degradation of all major plant cell wall polysaccharides except cellulose.

  90. 90.

    et al. Transfer of carbohydrate-active enzymes from marine bacteria to Japanese gut microbiota. Nature 464, 908–912 (2010). This work identifies an enzyme system that is involved in degrading a polysaccharide present in seaweed. This system was transferred from the marine metagenome to the human microbiome as a response to seaweed consumption.

  91. 91.

    , , , & Transcriptomic analyses of xylan degradation by Prevotella bryantii and insights into energy acquisition by xylanolytic bacteroidetes. J. Biol. Chem. 285, 30261–30273 (2010).

  92. 92.

    , , & Medium- to large-sized xylo-oligosaccharides are responsible for xylanase induction in Prevotella bryantii B14. Microbiology 151, 4121–4125 (2005).

  93. 93.

    et al. Whole genome analysis of the marine Bacteroidetes 'Gramella forsetii' reveals adaptations to degradation of polymeric organic matter. Environ. Microbiol. 8, 2201–2213 (2006).

  94. 94.

    et al. Novel features of the polysaccharide-digesting gliding bacterium Flavobacterium johnsoniae revealed by genome sequence analysis. Appl. Environ. Microbiol. 75, 6864–6875 (2009).

  95. 95.

    et al. The N-glycan glycoprotein deglycosylation complex (Gpd) from Capnocytophaga canimorsus deglycosylates human IgG. PLoS Pathog. 7, e1002118 (2011).

  96. 96.

    & SusG: a unique cell-membrane-associated α-amylase from a prominent human gut symbiont targets complex starch molecules. Structure 18, 200–215 (2010).

  97. 97.

    , , & Starch catabolism by a prominent human gut symbiont is directed by the recognition of amylose helices. Structure 16, 1105–1115 (2008). A report of the structure of SusD, the B. thetaiotaomicron starch-binding protein, revealing a novel fold and the site of glycan interaction in this broadly expanded family of bacteroidetes proteins.

  98. 98.

    et al. Dissecting the in vivo metabolic potential of two human gut acetogens. J. Biol. Chem. 285, 22082–22090 (2010).

  99. 99.

    & Cellulosomes: highly efficient nanomachines designed to deconstruct plant cell wall complex carbohydrates. Annu. Rev. Biochem. 79, 655–681 (2010).

  100. 100.

    , , & From cellulosomes to cellulosomics. Chem. Rec. 8, 364–377 (2008).

  101. 101.

    , & Carbohydrate metabolism in bifidobacteria. Genes Nutr. 6, 285–306 (2011).

  102. 102.

    , , & Spatial organization of bacterial flora in normal and inflamed intestine: a fluorescence in situ hybridization study in mice. World J. Gastroenterol. 11, 1131–1140 (2005).

  103. 103.

    , & The human commensal Bacteroides fragilis binds intestinal mucin. Anaerobe 17, 137–141 (2011).

  104. 104.

    & Formation of glycoprotein degrading enzymes by Bacteroides fragilis. FEMS Microbiol. Lett. 61, 289–293 (1991).

  105. 105.

    , & Genomic and metabolic studies of the impact of probiotics on a model gut symbiont and host. PLoS Biol. 4, e413 (2006).

  106. 106.

    et al. Alternative pathways for hydrogen disposal during fermentation in the human colon. Gut 31, 679–683 (1990).

  107. 107.

    et al. The Carbohydrate-Active EnZymes database (CAZy): an expert resource for glycogenomics. Nucleic Acids Res. 37, D233–D238 (2009).

  108. 108.

    et al. A catalog of reference genomes from the human microbiome. Science 328, 994–999 (2010).

  109. 109.

    & Slowly digestible starch: concept, mechanism, and proposed extended glycemic index. Crit. Rev. Food Sci. Nutr. 49, 852–867 (2009).

  110. 110.

    , & Classification and measurement of nutritionally important starch fractions. Eur. J. Clin. Nutr. 46 (Suppl. 2), S33–S50 (1992).

  111. 111.

    et al. Substrate-driven gene expression in Roseburia inulinivorans: importance of inducible enzymes in the utilization of inulin and starch. Proc. Natl Acad. Sci. USA 108 (Suppl. 1), 4672–4679 (2011).

  112. 112.

    et al. Effect of inulin on the human gut microbiota: stimulation of Bifidobacterium adolescentis and Faecalibacterium prausnitzii. Br. J. Nutr. 101, 541–550 (2009).

  113. 113.

    et al. Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia 50, 2374–2383 (2007).

  114. 114.

    , & Modulation of glucagon-like peptide 1 and energy metabolism by inulin and oligofructose: experimental data. J. Nutr. 137, S2547–S2551 (2007).

  115. 115.

    , , , & Chemopreventive potential of synergy1 and soybean in reducing azoxymethane-induced aberrant crypt foci in fisher 344 male rats. J. Nutr. Metab. 2011, 983038 (2011).

  116. 116.

    , , & Fermentation products of inulin-type fructans reduce proliferation and induce apoptosis in human colon tumour cells of different stages of carcinogenesis. Br. J. Nutr. 102, 663–671 (2009).

  117. 117.

    et al. Prebiotic effects of wheat arabinoxylan related to the increase in bifidobacteria, Roseburia and Bacteroides/Prevotella in diet-induced obese mice. PLoS ONE 6, e20944 (2011).

  118. 118.

    et al. Dietary modulation of clostridial cluster XIVa gut bacteria (Roseburia spp.) by chitin–glucan fiber improves host metabolic alterations induced by high-fat diet in mice. J. Nutr. Biochem. 23, 51–59 (2011).

  119. 119.

    et al. Arabinoxylans and inulin differentially modulate the mucosal and luminal gut microbiota and mucin-degradation in humanized rats. Environ. Microbiol. 13, 2667–2680 (2011).

  120. 120.

    et al. Essentials of Glycobiology (Cold Spring Harbor Lab. Press, 1999).

  121. 121.

    , , , & Histochemistry of the surface mucous gel layer of the human colon. Gut 40, 782–789 (1997).

  122. 122.

    et al. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc. Natl Acad. Sci. USA 105, 15064–15069 (2008).

  123. 123.

    et al. Proximal shift in the distribution of adenomatous polyps in Korea over the past ten years. Hepato-gastroenterology 56, 677–681 (2009).

  124. 124.

    & Trends in colorectal cancer incidence in Norway 1962–2006: an interpretation of the temporal patterns by anatomic subsite. Int. J. Cancer 126, 721–732 (2010).

  125. 125.

    , , , & Trends in colorectal cancer incidence by subsite in Osaka, Japan. Jpn J. Clin. Oncol. 39, 189–191 (2009).

  126. 126.

    , , , & Time trends in colon cancer incidence and distribution and lower gastrointestinal endoscopy utilization in Manitoba. Am. J. Gastroenterol. 103, 1249–1256 (2008).

  127. 127.

    et al. Mucolytic bacteria with increased prevalence in IBD mucosa augment in vitro utilization of mucin by other bacteria. Am. J. Gastroenterol. 105, 2420–2428 (2010).

  128. 128.

    , , , & Oxidation of hydrogen sulfide and methanediol to thiosulate by rat tissues: a specialized function of the colonic mucosa. Biochem. Pharmacol. 62, 255–259 (2001).

  129. 129.

    et al. Gut inflammation provides a respiratory electron acceptor for Salmonella. Nature 467, 426–429 (2010). This article demonstrates that tetrathionate, a metabolic by-product of the microbiota and human tissue combined, serves as an electron acceptor to enhance the physiology of a gut pathogen.

Download references

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).

Author information

Affiliations

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

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

Authors

  1. Search for Nicole M. Koropatkin in:

  2. Search for Elizabeth A. Cameron in:

  3. Search for Eric C. Martens in:

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Eric C. Martens.

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.

About this article

Publication history

Published

DOI

https://doi.org/10.1038/nrmicro2746

Further reading