The gut microbiome in health and in disease

Andrew B Shreiner, John Y Kao, Vincent B Young, Andrew B Shreiner, John Y Kao, Vincent B Young

Abstract

Purpose of review: Recent technological advancements and expanded efforts have led to a tremendous growth in the collective knowledge of the human microbiome. This review will highlight some of the important recent findings in this area of research.

Recent findings: Studies have described the structure and functional capacity of the bacterial microbiome in the healthy state and in a variety of disease states. Downstream analyses of the functional interactions between the host and its microbiome are starting to provide mechanistic insights into these interactions. These data are anticipated to lead to new opportunities for diagnosis, prognosis, and treatment of a variety of human diseases.

Summary: There is a fast growing collection of data describing the structure and functional capacity of the microbiome in a variety of conditions available to the research community for consideration and further exploration. Ongoing efforts to further characterize the functions of the microbiome and the mechanisms underlying host-microbe interactions will provide a better understanding of the role of the microbiome in health and disease.

References

    1. Robinson CJ, Bohannan BJ, Young VB. From structure to function: the ecology of host-associated microbial communities. Microbiol Mol Biol Rev. 2010 Sep;74(3):453–76. PubMed PMID: 20805407. Pubmed Central PMCID: 2937523. Epub 2010/09/02. eng.
    1. Bassis CM, Young VB, Schmidt TM. Methods for Characterizing Microbial Communities Associated With the Human Body. In: Fredricks DN, editor. The Human Microbiota: How Microbial Communities Affect Health and Disease. John Wiley & Sons, Inc.; Hoboken, New Jersey: 2013. pp. 51–74.
    1. Di Bella JM, Bao Y, Gloor GB, et al. High throughput sequencing methods and analysis for microbiome research. Journal of microbiological methods. 2013 Dec;95(3):401–14. PubMed PMID: 24029734.
    1. Kumar R, Eipers P, Little RB, et al. Getting started with microbiome analysis: sample acquisition to bioinformatics. Current protocols in human genetics / editorial board. 2014;82:18. Jonathan L Haines [et al] 8 1- 8 29. PubMed PMID: 25042718.
    1. Morgan XC, Huttenhower C. Meta'omic analytic techniques for studying the intestinal microbiome. Gastroenterology. 2014 May;146(6):1437–48. e1. PubMed PMID: 24486053.
    1. Human Microbiome Project C A framework for human microbiome research. Nature. 2012 Jun 14;486(7402):215–21. PubMed PMID: 22699610. Pubmed Central PMCID: 3377744.
    1. Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010 Mar 4;464(7285):59–65. PubMed PMID: 20203603. Pubmed Central PMCID: 3779803.
    1. Li J, Jia H, Cai X, et al. An integrated catalog of reference genes in the human gut microbiome. Nature biotechnology. 2014 Jul 6; PubMed PMID: 24997786. This article reports the most current and largest compilation to date of bacterial sequences combined from several large-scale metagenomic studies on the human gut microbiome. This catalog is an important resource for further exploration.
    1. Lozupone CA, Stombaugh JI, Gordon JI, et al. Diversity, stability and resilience of the human gut microbiota. Nature. 2012 Sep 13;489(7415):220–30. PubMed PMID: 22972295. Pubmed Central PMCID: 3577372.
    1. Human Microbiome Project C Structure, function and diversity of the healthy human microbiome. Nature. 2012 Jun 14;486(7402):207–14. PubMed PMID: 22699609. Pubmed Central PMCID: 3564958.
    1. Arumugam M, Raes J, Pelletier E, et al. Enterotypes of the human gut microbiome. Nature. 2011 May 12;473(7346):174–80. PubMed PMID: 21508958. Pubmed Central PMCID: 3728647.
    1. Ding T, Schloss PD. Dynamics and associations of microbial community types across the human body. Nature. 2014 May 15;509(7500):357–60. PubMed PMID: 24739969. The authors apply bioinformatics techniques to publicly available data sets demonstrating that shared microbial community types can be identified in spite of considerable variation between subjects. If different community types have biologic significance, there are implications for assessing and treating patients.
    1. Faith JJ, Guruge JL, Charbonneau M, et al. The long-term stability of the human gut microbiota. Science. 2013 Jul 5;341(6141):1237439. PubMed PMID: 23828941. Pubmed Central PMCID: 3791589. This study characterizes the human gut microbiota over time, and it provides important new evidence that the microbiota of an individual is quite stable over years and likely decades.
    1. Larsbrink J, Rogers TE, Hemsworth GR, et al. A discrete genetic locus confers xyloglucan metabolism in select human gut Bacteroidetes. Nature. 2014 Feb 27;506(7489):498–502. PubMed PMID: 24463512. This study demonstrates that a common dietary fiber is metabolized by a select few bacterial species that are commonly present in the human gut microbiota, illustrating the concept of human-microbe symbiosis.
    1. Belcheva A, Irrazabal T, Robertson SJ, et al. Gut microbial metabolism drives transformation of msh2-deficient colon epithelial cells. Cell. 2014 Jul 17;158(2):288–99. PubMed PMID: 25036629. This study provides evidence that butyrate promotes colon tumorigenesis in a mouse model of APC gene mutation and MSH2 gene depletion.
    1. Singh N, Gurav A, Sivaprakasam S, et al. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity. 2014 Jan 16;40(1):128–39. PubMed PMID: 24412617. This study provides evidence that butyrate inhibits colon tumorigenesis in mouse models of APC gene mutation or colitis.
    1. Arpaia N, Campbell C, Fan X, et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 2013 Dec 19;504(7480):451–5. PubMed PMID: 24226773. Pubmed Central PMCID: 3869884.
    1. Atarashi K, Tanoue T, Oshima K, et al. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature. 2013 Aug 8;500(7461):232–6. PubMed PMID: 23842501. Using a novel strategy to identify bacterial communities from the human gut microbiota that promote Treg development, the authors identify 17 strains of non-pathogenic Clostridia capable of inducing Treg. This approach is instructive for the rational design of probiotic therapies.
    1. Atarashi K, Tanoue T, Shima T, et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science. 2011 Jan 21;331(6015):337–41. PubMed PMID: 21205640. Pubmed Central PMCID: 3969237.
    1. Furusawa Y, Obata Y, Fukuda S, et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. 2013 Dec 19;504(7480):446–50. PubMed PMID: 24226770.
    1. Narushima S, Sugiura Y, Oshima K, et al. Characterization of the 17 strains of regulatory T cell-inducing human-derived Clostridia. Gut microbes. 2014 Mar 18;5(3) PubMed PMID: 24642476.
    1. Smith PM, Howitt MR, Panikov N, et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 2013 Aug 2;341(6145):569–73. PubMed PMID: 23828891. Pubmed Central PMCID: 3807819.
    1. Faith JJ, Ahern PP, Ridaura VK, et al. Identifying gut microbe-host phenotype relationships using combinatorial communities in gnotobiotic mice. Science translational medicine. 2014 Jan 22;6(220):220ra11. PubMed PMID: 24452263. Pubmed Central PMCID: 3973144.These authors describe another unbiased novel method for identifying bacterial strains capable of inducing Treg.
    1. Kamada N, Nunez G. Regulation of the immune system by the resident intestinal bacteria. Gastroenterology. 2014 May;146(6):1477–88. PubMed PMID: 24503128. Pubmed Central PMCID: 3995843.
    1. Scher JU, Sczesnak A, Longman RS, et al. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. eLife. 2013;2:e01202. PubMed PMID: 24192039. Pubmed Central PMCID: 3816614.
    1. Kostic AD, Chun E, Robertson L, et al. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell host & microbe. 2013 Aug 14;14(2):207–15. PubMed PMID: 23954159. Pubmed Central PMCID: 3772512.
    1. Le Chatelier E, Nielsen T, Qin J, et al. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013 Aug 29;500(7464):541–6. PubMed PMID: 23985870.
    1. Karlsson FH, Tremaroli V, Nookaew I, et al. Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature. 2013 Jun 6;498(7452):99–103. PubMed PMID: 23719380.
    1. Wang Z, Klipfell E, Bennett BJ, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011 Apr 7;472(7341):57–63. PubMed PMID: 21475195. Pubmed Central PMCID: 3086762.
    1. Tang WH, Wang Z, Levison BS, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. The New England journal of medicine. 2013 Apr 25;368(17):1575–84. PubMed PMID: 23614584. Pubmed Central PMCID: 3701945. This study shows that ingestion of phosphatidylcholine leads to elevated plasma TMAO levels in healthy humans unless their microbiota was depleted first with antibiotics. Next, they show that plasma TMAO levels were associated with increased risk for cardiovascular events in humans with cardiovascular disease risk factors.
    1. Koeth RA, Wang Z, Levison BS, et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nature medicine. 2013 May;19(5):576–85. PubMed PMID: 23563705. Pubmed Central PMCID: 3650111 This study provides further evidence for microbiota metabolism of dietary substrates in the production of the proatherogenic molecule, TMAO. In testing omnivorous and vegan human subjects, the provide evidence for a possible link between microbiota composition, red meat consumption and cardiovascular disease risk.
    1. Simren M, Barbara G, Flint HJ, et al. Intestinal microbiota in functional bowel disorders: a Rome foundation report. Gut. 2013 Jan;62(1):159–76. PubMed PMID: 22730468. Pubmed Central PMCID: 3551212.
    1. Halmos EP, Christophersen CT, Bird AR, et al. Diets that differ in their FODMAP content alter the colonic luminal microenvironment. Gut. 2014 Jul 12; PubMed PMID: 25016597.
    1. Halmos EP, Power VA, Shepherd SJ, et al. A diet low in FODMAPs reduces symptoms of irritable bowel syndrome. Gastroenterology. 2014 Jan;146(1):67–75. e5. PubMed PMID: 24076059. In this randomized, controlled, single-blind, cross-over study, a low FOMAP diet improved symptoms in patients with IBS. This is further evidence for the use of low FODMAP diet in the treatment of IBS.
    1. Tillisch K, Labus J, Kilpatrick L, et al. Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology. 2013 Jun;144(7):1394–401. 401 e1-4. PubMed PMID: 23474283. Pubmed Central PMCID: 3839572.
    1. Britton RA, Young VB. Role of the intestinal microbiota in resistance to colonization by Clostridium difficile. Gastroenterology. 2014 May;146(6):1547–53. PubMed PMID: 24503131. Pubmed Central PMCID: 3995857.
    1. Kassam Z, Lee CH, Yuan Y, et al. Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. The American journal of gastroenterology. 2013 Apr;108(4):500–8. PubMed PMID: 23511459.
    1. van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. The New England journal of medicine. 2013 Jan 31;368(5):407–15. PubMed PMID: 23323867. In a randomized, controlled trial for the treatment of recurrent Clostridium difficile infection, fecal microbiota transplant plus vancomycin was clearly superior to vancomycin alone. FMT is increasingly recognized as an effective therapy for CDI.
    1. Seekatz AM, Aas J, Gessert CE, et al. Recovery of the gut microbiome following fecal microbiota transplantation. mBio. 2014;5(3):e00893–14. PubMed PMID: 24939885. Pubmed Central PMCID: 4068257. This study describes the resulting microbiota in recipients of FMT for CDI.
    1. Petrof EO, Gloor GB, Vanner SJ, et al. Stool substitute transplant therapy for the eradication of Clostridium difficile infection: 'RePOOPulating' the gut. Microbiome. 2013;1(1):3. PubMed PMID: 24467987. Pubmed Central PMCID: 3869191. As a potential step forward in the use of FMT for recurrent CDI, these authors demonstrate efficacy in the treatment of recurrent CDI for fecal bacterial strains that were cultured and purified before transfer.
    1. Theriot CM, Koenigsknecht MJ, Carlson PE, Jr., et al. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection. Nature communications. 2014;5:3114. PubMed PMID: 24445449. Pubmed Central PMCID: 3950275. This preclinical study provides new mechanistic information explaining how C. difficile may infect the antibiotic treated host.
    1. Kostic AD, Xavier RJ, Gevers D. The microbiome in inflammatory bowel disease: current status and the future ahead. Gastroenterology. 2014 May;146(6):1489–99. PubMed PMID: 24560869. Pubmed Central PMCID: 4034132.
    1. Gevers D, Kugathasan S, Denson LA, et al. The treatment-naive microbiome in new-onset Crohn's disease. Cell host & microbe. 2014 Mar 12;15(3):382–92. PubMed PMID: 24629344. Pubmed Central PMCID: 4059512. Using a large cohort of new-onset, treatment-naive pediatric Crohn's disease patients, this case-control study describes early CD-associated features of the intestinal microbiome. The finding that rectal, but not fecal, microbiota differentiated CD and healthy patients may have diagnostic implications.
    1. Haberman Y, Tickle TL, Dexheimer PJ, et al. Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature. The Journal of clinical investigation. 2014 Aug 1;124(8):3617–33. PubMed PMID: 25003194. Pubmed Central PMCID: 4109533. In a large case-control study of new-onset, treatment-naive IBD pediatric patients, the authors identify patterns of ileal host gene expression and ileal microbiome that are unique to CD patients irrespective of the presence of ileal inflammation. These data on early changes in the microbiota and host response may support the hypothesis that dysbiosis contributes to the development of IBD in susceptible individuals.
    1. Anderson JL, Edney RJ, Whelan K. Systematic review: faecal microbiota transplantation in the management of inflammatory bowel disease. Alimentary pharmacology & therapeutics. 2012 Sep;36(6):503–16. PubMed PMID: 22827693.
    1. Kump PK, Grochenig HP, Lackner S, et al. Alteration of intestinal dysbiosis by fecal microbiota transplantation does not induce remission in patients with chronic active ulcerative colitis. Inflammatory bowel diseases. 2013 Sep;19(10):2155–65. PubMed PMID: 23899544.

Source: PubMed

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