The Gut Microbiome and Beyond

Impact of Microbial Imbalance on Human Health


The gut microbiome is a vast, complex ecosystem that is at the forefront of extensive research.1,2 Our understanding of the intricacies of the gut microbiome is unfolding at a rapid pace.1,3 New discoveries in this field have the potential to change how we think about GI health and revolutionize how we treat GI disease.1,4-6

The Gut Microbiome and Beyond was created to distill the expanding body of clinical and scientific information about the gut microbiome.

GI = gastrointestinal.

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References

  • Sidhu M, van der Poorten D. The gut microbiome. Aust Fam Physician. 2017;46(4):206-211.
  • Lloyd-Price J, Abu-Ali G, Huttenhower C. The healthy human microbiome. Genome Med. 2016;8(1):51.
  • Huang X, Fan X, Ying J, Chen S. Emerging trends and research foci in gastrointestinal microbiome. J Transl Med. 2019;17(1):67.
  • Cresci GA, Bawden E. The Gut microbiome: what we do and don’t know. Nutr Clin Pract. 2015;30(6):734-746.
  • Cani PD. Human gut microbiome: hopes, threats and promises. Gut. 2018;67(9):1716-1725.
  • Gorkiewicz G, Moschen A. Gut microbiome: a new player in gastrointestinal disease. Virchows Arch. 2018;472(1):159-172.

Exploring the Human Gut Microbiome


The gut microbiome has the largest population of microorganisms in the body, the majority of which are bacteria.1-3 It consists of more than 1000 bacterial species that are differentially abundant across the GI tract.3-5

The four major bacterial phyla that populate a healthy gut microbiome4 are Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria.

Although the gut microbiome tends to remain stable over time,3,6 changes in microbial composition can have physiologic effects that may impact health.7-9

GI = gastrointestinal.

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  • Lloyd-Price J, Abu-Ali G, Huttenhower C. The healthy human microbiome. Genome Med. 2016;8:51.
  • Ursell LK, Metcalf JL, Parfrey LW, Knight R. Defining the human microbiome. Nutr Rev. 2012;70(empl 1):S38-S44.
  • Sidhu M, van der Poorten D. The gut microbiome. Aust Fam Physician. 2017;46(4):206-211.
  • Ringel Y. The gut microbiome in irritable bowel syndrome and other functional bowel disorders. Gastroenterol Clin North Am. 2017;46(1):91-101.
  • Quigley EM. Gut bacteria in health and disease. Gastroenterol Hepatol. 2013;9(9):560-569.
  • Raskov H, Burcharth J, Pommergaard HC, Rosenberg J. Irritable bowel syndrome, the microbiota and the gut-brain axis. Gut Microbes. 2016;7(5):365-383.
  • Passos MDCF, Moraes-Filho JP. Intestinal microbiota in digestive diseases. Arq Gastroenterol. 2017;54(3):255-262.
  • Distrutti E, Monaldi L, Ricci P, Fiorucci S. Gut microbiota role in irritable bowel syndrome: new therapeutic strategies. World J Gastroenterol. 2016;22(7):2219-2241.
  • Flint HJ, Scott KP, Louis P, Duncan SH. The role of the gut microbiota in nutrition and health. Nat Rev Gastroenterol Hepatol. 2012;9(10):577-589.
  • Gorkiewicz G. Moschen A. Gut microbiome: a new player in gastrointestinal disease. Virchows Arch. 2018;472:159-172.
  • Dong TS, Gupta A. Influence of early life, diet, and the environment on the microbiome. Clin Gastroenterol Hepatol. 2019;17(2):231-242.
  • Cresci GA, Bawden E. Gut microbiome: what we do and don’t know. Nutr Clin Pract. 2015;30(6):734-746.
  • Shin A, Preidis GA, Shulman R, Kashyap PC. The gut microbiome in adult and pediatric functional gastrointestinal disorders. Clin Gastroenterol Hepatol. 2019;17(2):256-274.
  • Carding S, Verbeke K, Vipond DT, Corfe BM, Owen LJ. Dysbiosis of the gut microbiota in disease. Microb Ecol Health Dis. 2015;26:26191.
  • Wang B, Yao M, Lv L, Ling Z, Li L. The human microbiota in health and disease. Engineering. 2017;3:71-82.
  • Jandhyala SM, Talukdar R, Subramanyam C, Vuyyuru H, Sasikala M, Reddy DN. Role of the normal gut microbiota. World J Gastroenterol. 2015;21(29):8787-8803.
  • Cani PD. Human gut microbiome: hopes, threats, and promises. Gut. 2018;67:1716-1725.
  • Ghoshal UC, Shukla R, Ghoshal U, Gwee KA, Ng SC, Quigley EM. The gut microbiota and irritable bowel syndrome: friend or foe? Int J Inflam. 2012;2012:151085.
  • Kennedy PJ, Cryan JF, Dinan TG, Clarke G. Irritable bowel syndrome: a microbiome-gut-brain axis disorder? World J Gastroenterol. 2014;20(39):14105-14125.
  • Tillisch K. The effects of gut microbiota on CNS functions in humans. Gut Microbes. 2014;5(3):404-410.
  • Brett BE, de Weerth C. The microbiota-gut-brain axis: a promising avenue to foster healthy development outcomes. [published online ahead of print January 14, 2019]. Dev Psychobiol. doi:10.1002/dev.21824.
  • Forbes JD, Van Domselaar G, Bernstein CN. The gut microbiota in immune-mediated inflammatory diseases. Front Microbiol. 2016; 7:1081.
  • Lee KN, Lee OY. Intestinal microbiota in pathophysiology and management of irritable bowel syndrome. World J Gastroenterol. 2014;20(27):8886-8897.

Causes and Consequences of Gut Dysbiosis


Innate and environmental factors (eg, hygiene, diet, drug use, exposure to pathogens) can alter the gut microbiome.1,2 Studies suggest that an imbalance in gut microbiota, or dysbiosis, can affect the symbiotic relationship between the microbiota and host, creating an environment susceptible to disease.3-5 New research implicates this imbalance with a number of GI diseases.4,6

GI = gastrointestinal.

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  • Carding S, Verbeke K, Vipond DT, Corfe BM, Owen LJ. Dysbiosis of the gut microbiota in disease. Microb Ecol Health Dis. 2015;26:26191.
  • Sommer F, Bäckhed F. The gut microbiota—masters of host development and physiology. Nat Rev Microbiol. 2013;11:227-238.
  • Distrutti E, Monaldi L, Ricci P, Fiorucci S. Gut microbiota role in irritable bowel syndrome: new therapeutic strategies. World J Gastroenterol. 2016;22(7):2219-2241.
  • Passos MDCF, Moraes-Filho JP. Intestinal microbiota in digestive diseases. Arq Gastroenterol. 2017;54(3):255-262.
  • Ghoshal UC, Shukla R, Ghoshal U, Gwee KA, Ng SC, Quigley EM. The gut microbiota and irritable bowel syndrome: friend or foe? Int J Inflam. 2012;2012:151085.
  • Blum HE. The human microbiome. Adv Med Sci. 2017;62(2):414-420.
  • Cresci GA. The gut microbiome: what we do and don’t know. Nutr Clin Pract. 2015;30(6):734-746.
  • Dong TS, Gupta A. Influence of early life, diet, and the environment on the microbiome. Clin Gastroenterol Hepatol. 2019;17(2):231-242.
  • Singh RK, Chang HW, Yan D, et al. Influence of diet on the gut microbiome and implications for human health. J Transl Med. 2017;15(1):73.
  • Desai MS, Seekatz AM, Koropatkin NM, et al. A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell. 2016;167(5):1339-1353.
  • Makki K, Deehan EC, Walter J, Bäckhed F. The impact of dietary fiber on gut microbiota in host health and disease. Cell Host Microbe. 2018;23(6):705-715.
  • Wang B, Yao M, Lv L, et al. The human microbiota in health and disease. Engineering. 2017;3(1):71-82.
  • Pham TAN, Lawley TD. Emerging insights on intestinal dysbiosis during bacterial infections. Curr Opin Microbiol. 2014;17:67-74.
  • Flint HJ, Scott KP, Louis P, Duncan SH. The role of the gut microbiota in nutrition and health. Nat Rev Gastroenterol Hepatol. 2012;9(10):577-589.
  • Raskov H, Burcharth J, Pommergaard HC, Rosenberg J. Irritable bowel syndrome, the microbiota and the gut-brain axis. Gut Microbes. 2016;7(5):365-383.
  • Rinninella E, Raoul P, Cintoni M, et al. What is the healthy gut microbiota composition? A changing ecosystem across age, environment, diet, and diseases. Microorganisms. 2019;7(1):14.
  • Kennedy PJ, Cryan JF, Dinan TG, Clarke G. Irritable bowel syndrome: a microbiome-gut-brain axis disorder? World J Gastroenterol. 2014;20(39):14105-14125.
  • Jandhyala SM, Talukdar R, Subramanyam C, Vuyyuru H, Sasikala M, Reddy DN. Role of the normal gut microbiota. World J Gastroenterol. 2015;21(29):8787-8803.
  • Francino MP. Antibiotics and the human gut microbiome: dysbioses and accumulation of resistances. Front Microbiol. 2016;6:1543.
  • Biedermann L, Zeitz J, Mwinyi J, et al. Smoking cessation induces profound changes in the composition of the intestinal microbiota in humans. PloS One. 2013;8(3):e59260.
  • Shin A, Preidis GA, Shulman R, Kashyap PC. The gut microbiome in adult and pediatric functional gastrointestinal disorders. Clin Gastroenterol Hepatol. 2019;17(2):256-274.
  • Mutlu EA, Gillevet PM, Rangwala H, et al. Colonic microbiome is altered in alcoholism. Am J Physiol Gastrointest Liver Physiol. 2012;302(9):G966-G978.
  • Gorkiewicz G, Moschen A. Gut microbiome: a new player in gastrointestinal disease. Virchows Arch. 2018;417:159-172.
  • Nouvenne A, Ticinesi A, Tana C, et al. Digestive disorders and intestinal microbiota. Acta Biomed. 2018;89(9):47-51.
  • Cho I, Blaser MJ. The human microbiome: at the interface of health and disease. Nat Rev Genet. 2012;13(4):260-270.
  • Lanas A, Abad-Baroja D, Lanas-Gimeno A. Progress and challenges in the management of diverticular disease: which treatment? Therap Adv Gastroenterol. 2018;11:1-21. doi:10.1177/1756284818789055.

Microbial Imbalance in IBS


Various lines of evidence support the role of gut microbiota in the pathogenesis of IBS.1-3 Microbial imbalance may be linked to changes in gut permeability, motility, visceral perception, and immune response, ultimately causing IBS symptoms.4-8 Significant differences in microbial composition have been observed in patients with IBS compared with healthy individuals.9,10 Additionally, epidemiologic studies of infectious enteritis (food poisoning) and post-infectious IBS support the association between gut dysbiosis and the development of IBS symptoms.1,2,11 This evidence has led to the use of therapies and interventions for IBS that modulate gut microbiota.12,13

IBS = irritable bowel syndrome.

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  • Ringel Y. The gut microbiome in irritable bowel syndrome and other functional bowel disorders. Gastroenterol Clin North Am. 2017;46(1):91-101.
  • Klem F, Wadhwa A, Prokop LJ, et al. Prevalence, risk factors, and outcomes of irritable bowel syndrome after infectious enteritis: a systematic review and meta-analysis. Gastroenterology. 2017;152(5):1042-1054.
  • DuPont HL. Evidence for the role of gut microbiota in irritable bowel syndrome and its potential influence on therapeutic targets. Aliment Pharmacol Ther. 2014;39(10):1033-1042.
  • Lee KN, Lee OY. Intestinal microbiota in pathophysiology and management of irritable bowel syndrome. World J Gastroenterol. 2014;20(27):8886-8897.
  • Zhuang X, Xiong L, Li L, Li M, Chen M. Alterations of gut microbiota in patients with irritable bowel syndrome: a systematic review and meta-analysis. J Gastroenterol Hepatol. 2017;32(1):28-38.
  • Passos MDCF, Moraes-Filho JP. Intestinal microbiota in digestive diseases. Arq Gastroenterol. 2017;54(3):255-262.
  • Ghoshal UC, Shukla R, Ghoshal U, Gwee KA, Ng SC, Quigley EM. The gut microbiota and irritable bowel syndrome: friend or foe? Int J Inflam. 2012;2012:151085.
  • Stern EK, Brenner DM. Gut microbiota-based therapies for irritable bowel syndrome. Clin Transl Gastroenterol. 2018;9(2):2-7.
  • Posserud I, Stotzer PO, Björnsson ES, Abrahamsson H, Simrén M. Small intestinal bacterial overgrowth in patients with irritable bowel syndrome. Gut. 2007;56(6):802-808.
  • Giamarellos-Bouboulis E, Tang J, Pyleris E, et al. Molecular assessment of differences in duodenal microbiome in subjects with irritable bowel syndrome. Scand J Gastroenterol. 2015;50(9):1076-1087.
  • Pimentel M, Morales W, Pokkunuri V et al. Autoimmunity links vinculin to the pathophysiology of chronic functional bowel changes following campylobacter jejuni infection in a rat model. Dig Dis Sci. 2015;60:1195-1205.
  • Menees S, Chey W. The gut microbiome and irritable bowel syndrome. F1000Research. 2018;7(F1000 Faculty Rev):1029.
  • Harris LA, Baffy N. Modulation of the gut microbiota: a focus on treatments for irritable bowel syndrome. Postgrad Med. 2017;129(8):872-888.
  • Kassinen A, Krogius-Kurikka L, Mäkivuokko H, et al. The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects. Gastroenterology. 2007;133(1):24-33.
  • Carroll IM, Ringel-Kulka T, Keku TO, et al. Molecular analysis of the luminal- and mucosal-associated intestinal microbiota in diarrhea-predominant irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol. 2011;301(5):G799-G807.
  • Carroll IM, Ringel-Kulka T, Siddle JP, Ringel Y. Alterations in composition and diversity of the intestinal microbiota in patients with diarrhea-predominant irritable bowel syndrome. Neurogastroenterol Motil. 2012;24(6):5-11.
  • Tap J, Derrien M, Törnblom H, et al. Identification of an intestinal microbiota signature associated with severity of irritable bowel syndrome. Gastroenterology. 2017;152(1):111-123.
  • Pyleris E, Giamarellos-Bourboulis EJ, Tzivras D, Koussoulas V, Barbatzas C, Pimentel M. The prevalence of overgrowth by aerobic bacteria in the small intestine by small bowel culture: relationship with irritable bowel syndrome. Dig Dis Sci. 2012;57(5):1-9.
  • König J, Brummer RJ. Alteration of the intestinal microbiota as a cause of and a potential therapeutic option in irritable bowel syndrome. Beneficial Microbes. 2014;5(3):247-261.
  • Raskov H, Burcharth J, Pommergaard HC, Rosenberg J. Irritable bowel syndrome, the microbiota and the gut-brain axis. Gut Microbes. 2016;7(5):365-383.
  • Ohkusa T, Koldo S, Nishikawa Y, Sato N. Gut microbiota and chronic constipation: A review and update. Front Med. 2019;6(19): doi: 10.3389/fmed.2019.00019.
  • Distrutti E, Monaldi L, Ricci P, Fiorucci S. Gut microbiota role in irritable bowel syndrome: new therapeutic strategies. World J Gastroenterol. 2016;22(7):2219-2241.
  • Kennedy PJ, Cryan JF, Dinan TG, Clarke G. Irritable bowel syndrome: a microbiome-gut-brain axis disorder? World J Gastroenterol. 2014;20(39):14105-14125.
  • Quigley EMM. Gut bacteria in health and disease. Gastroenterol Hepatol. 2013;9(9):560-569.
  • Fan WT, Ding C, Xu NN, Zong S, Ma P, Gu B. Close association between intestinal microbiota and irritable bowel syndrome. Eur J Clin Microbiol Infect Dis. 2017;36(12):2303-2317.
  • Mayer EA, Tillisch K, Gupta A. Gut/brain axis and the microbiota. J Clin Invest. 2015;125(3):926-938.
  • Quigley EMM. The gut-brain axis and the microbiome: clues to pathophysiology and opportunities for novel management strategies in irritable bowel syndrome (IBS). J Clin Med. 2018;7(1). doi:10.3390/jcm7010006.
  • Skonieczna-Zydecka K, Marlicz W, Misera A, Koulaouzidis A, Loniewski I. Microbiome – the missing link in the gut-brain axis: focus on its role in gastrointestinal and mental health. J Clin Med. 2018;7(12). doi:10.3390/jcm7120521.

Microbial Imbalance in IBD


IBD is a complex, multifactorial group of disorders characterized by chronic, relapsing inflammation in the gut.1-4 The pathophysiology of IBD may involve an inappropriate immune response to gut microbiota in genetically susceptible individuals.1-3 This etiology is supported by the characterization of compositional differences in the gut microbiome, as observed in studies of patients with IBD compared with healthy individuals. These differences include1,2,4,5:

  • Reduced bacterial diversity
  • A shift in the proportion of commensal and potentially pathogenic microorganisms

Exploration of gut microbiome-based diagnostics and therapeutics can help support future research of the causal relationship between gut dysbiosis and IBD.1,2,4

IBD = Inflammatory bowel disease.

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  • Somineni HK, Kugathasan S. The microbiome in patients with inflammatory disease. Clin Gastroenterol Hepatol. 2018;17:243-255.
  • Zuo T, Ng SC. The gut microbiota in the pathogenesis and therapeutics of inflammatory bowel disease. Front Microbiol. 2018;9:2247.
  • Weingarden AR, Vaughn BP. Intestinal microbiota, fecal microbiota transplantation, and inflammatory bowel disease. Gut Microbes. 2017;8(3):238-252.
  • Yu LCH. Microbiota dysbiosis and barrier dysfunction in inflammatory bowel disease and colorectal cancers: exploring a common ground hypothesis. J Biomed Sci. 2018;25:79.
  • Casen C, Vebo HC, Sekelja M, et al. Deviations in human gut microbiota: a novel diagnostic test for determining dysbiosis in patients with IBS or IBD. Alim Pharmacol Ther. 2015;42:71-83.
  • Frank DN, St Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel disease. Proc Natl Acad Sci USA. 2007;104(34):13780-13785.
  • Halfvarson J, Brislawn CJ, Lamendella R, et al. Dynamics of the human gut microbiome in inflammatory bowel disease. Nat Microbiol. 2017;2:17004.
  • Morgan XC, Tickle TL, Sokol H, et al. Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol. 2012;13(9):R79.
  • Li J, Butcher J, Mack D, Stintzi A. Functional impacts of the intestinal microbiome in the pathogenesis of inflammatory bowel disease. Inflamm Bowel Dis. 2015;21(1):139-153
  • Sartor RB, Wu GD. Roles for intestinal bacteria, viruses, and fungi in pathogenesis of inflammatory bowel diseases and therapeutic approaches. Gastroenterology. 2017;152(2):327-339.

Microbial Imbalance in CLD


Improvements in gut microbiome analysis have enhanced our understanding of liver disease.1 We now know that microbial imbalance plays a role in the onset, progression, and complications of liver disease.1,2 Studies have shown that patients with CLD display a pattern of dysbiosis represented by a decrease in autochthonous taxa (eg, Firmicutes) and an increase in pathogenic taxa.1-4 The contribution of gut microbiota to disease pathogenesis increases as liver disease progresses, making it an important therapeutic target in the management of cirrhosis.2,3

CLD = chronic liver disease.

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  • Acharya C, Bajaj JS. Gut microbiota and complications of liver disease. Gastroenterol Clin North Am. 2017;46(1):155-169.
  • Oikonomou T, Papatheodoridis GV, Samarkos M, Goulis I, Cholongitas E. Clinical impact of microbiome in patients with decompensated cirrhosis. World J Gastroenterol. 2018;24(34):3813-3820.
  • Acharya C, Bajaj JS. Altered microbiome in patients with cirrhosis and complications. Clin Gastroenterol Hepatol. 2019;17:307-321.
  • Bajaj JS, Heuman DM, Hylemon PB, et al. Altered profile of human gut microbiome is associated with cirrhosis and its complications. J Hepatol. 2014;60(5):940-947.
  • Minemura M, Shimizu Y. Gut microbiota and liver diseases. World J Gastroenterol. 2015;21(6):1691-1702.
  • Boursier J, Mueller O, Barret M, et al. The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota. Hepatology. 2016;63(3):764-775.
  • Vilstrup H, Amodio P, Bajaj J, et al. Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014;60(2):715-735.

Assimilation Into Clinical Practice


Over the past two decades, advancements in DNA sequencing technology have enhanced our understanding of the role of the gut microbiome in health and disease. These advances sparked interest in the potential use of microbiome-based diagnostics and therapeutics in clinical practice.1 Furthermore, clinicians commonly receive questions about the gut microbiome from their patients because of direct-to-consumer marketing and the commercialization of microbiome-based testing. As a result, it is important to stay current on advances in this rapidly evolving field.1,2

DNA = deoxyribonucleic acid.

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  • Staley C, Kaiser T, Khoruts A. Clinician guide to microbiome testing. Dig Dis Sci. 2018;63:3167-3177.
  • Ananthakrishnan AN, Singal AG, Chang L. The gut microbiome and digestive health – a new frontier. Clin Gastroenterol Hepatol. 2019;17:215-217.
 
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