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Table of Contents
EDITORIAL
Year : 2021  |  Volume : 13  |  Issue : 1  |  Page : 1-5

Gut microbiota: Poised to assume an overarching role in a wide range of diseases


Department of Medicine, University of Nigeria Teaching Hospital, Enugu, Nigeria

Date of Submission29-May-2021
Date of Decision29-May-2021
Date of Acceptance29-May-2021
Date of Web Publication30-Jun-2021

Correspondence Address:
Prof. Sylvester Chuks Nwokediuko
Department of Medicine, University of Nigeria Teaching Hospital, Ituku, Ozalla, PMB 01129 Enugu
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/njgh.njgh_4_21

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How to cite this article:
Nwokediuko SC. Gut microbiota: Poised to assume an overarching role in a wide range of diseases. Niger J Gastroenterol Hepatol 2021;13:1-5

How to cite this URL:
Nwokediuko SC. Gut microbiota: Poised to assume an overarching role in a wide range of diseases. Niger J Gastroenterol Hepatol [serial online] 2021 [cited 2021 Dec 4];13:1-5. Available from: https://www.njghonweb.org/text.asp?2021/13/1/1/320306




  Introduction Top


Over 2000 years ago, Hippocrates, the father of modern medicine propounded the theory that every disease starts from the gut. At the time this statement was made, research evidence as we have it today was not in good supply. However, we now know that there is an intricate relationship between gut health and the overall health of the individual.

The gut is home to a large number of microorganisms which make up the gut microbiota.[1],[2] This is an intricate and dynamic system which has been conceptualized as a separate organ within the human body that provides many vital functions.[3] Most of these organisms cannot be cultured with the standard microbiological techniques. Our understanding of gut microbiota has been revolutionized by advances in high throughput DNA sequencing technology and bioinformatics. Bioinformatics combines computer science, molecular biology, biotechnology, statistics, and engineering. The high throughput DNA technology utilizes omic technologies in the detection of genes, mRNA, proteins, and metabolites.

Four major phyla dominate the human gut microbiota: Firmicutes, Bacteroitetes, Proteobacteria, and Actinobacteria. The first two are the most abundant. Other minor phyla include Verrucomicrobia and Fusobacteria.[4] The chemical, nutritional, and immunological gradients along the gut affect the density and diversity of gut microbiota. Thus, a gradient exists vertically and horizontally. On the horizontal axis is the observation that luminal organisms differ from those attached to the epithelium. Whereas the former is thought to be responsible for metabolic and nutritional activities, the latter plays greater role in immune function. Similarly, there is a vertical gradient of microbiota density in the gut,[5],[6] with the stomach and duodenum harboring very low numbers because of gastric and pancreatic secretions and enzymes. The number gradually increases in the small bowel, reaching its highest concentration (up to 1011-1013 bacteria/g) in the colon where anaerobes predominate.[5],[7]

Initially, the gut microbiome was thought to have a limited role in the digestion of complex carbohydrates and in synthesizing Vitamins and nutrients. Currently, this new organ is known to govern host physiology by regulating metabolism, immunity, and gut-brain axis, through signaling of bioactive metabolites generated by the microbiome. It thus functions such as an endocrine organ secretes bioactive metabolites that can affect host physiology directly or indirectly.[8]

Disturbance in density and diversity of gut microbiota (dysbiosis) has been reported in a wide range of medical conditions, including cancer, metabolic diseases (such as obesity and diabetes), inflammatory conditions, cardiovascular diseases, and neurodegenerative conditions. There is, thus, not only a potential diagnostic utility of this burgeoning field but also the microbiome holds great promise as an exciting new target for diet-based prevention and treatment of disease.


  Physiological Functions of Gut Microbiota Top


Gut microbiota plays key roles in maintaining the metabolic, nutritional, structural, and immunological processes of the body.

Nutrition and metabolism

Both the microbiome and host genome participate in encoding for metabolites, with the former contributing much more than the latter. Specific functions of gut microbiota include extraction of energy from otherwise indigestible polysaccharides as well as promotion of uptake of nutrients. Extraction of energy from dietary polysaccharide and fiber leads to the production of short-chain fatty acids (SCFAs), Vitamins, and essential amino acids.[9],[10]

SCFAs serve as nourishment for the microbiota and host intestinal cells and regulate immunity, energy metabolism, and expansion of adipose tissue. They also acidify the intestinal lumen, thus preventing the growth of pathogenic organisms.[11],[12] The major SCFAs are acetate, butyrate, and propionate. Acetate is a substrate for gluconeogenesis and lipogenesis while butyrate and propionate regulate gut physiology and immunological processes. Gamma aminobutyric acid, tryptophan, serotonin, and catecholamines are other metabolic products of gut microbiota that function essentially as signaling molecules. Other functions of SCFAs include modulation of appetite regulation and energy intake,[13] and maintenance of epithelial integrity through the action of interleukin-18.[14]

Bile acids from dietary cholesterol are also metabolized by gut microbiota to prevent excessive weight gain and development of nonalcoholic fatty liver disease (NAFLD),[15] reduce insulin resistance[16], and also reduce diet-induced obesity.[16],[17]

Defense against pathogens

Gut microbiota defends the host against pathogens through diverse mechanisms, including the production of antimicrobial compounds and colonization resistance.

Structural function

Gut microbiota plays a key role in the development, maturation and maintenance of the sensory, motor, intestinal barrier, and immune functions of the mucosa. Through the mechanism of competitive exclusion by the occupation of sites of attachment, competition for nutrients and production of antimicrobial compounds, the gut microbiota acts as a physical barrier to in-coming pathogenic organisms. Furthermore, gut microbiota stimulates the host to produce a wide range of antimicrobial compounds such as defensins, cathelicidins, and C-type lectins.[18],[19]

Immunological function

The intestinal mucosa presents a very wide surface for interaction with antigen from the external environment. The dense microbiota in contact with the mucosa accounts for the bulk of antigens that confront the native immune cells. The immune system develops tolerance to overlying microbiota while at the same time controls the microbiota to prevent its overgrowth, translocation, and systemic dissemination.

Bacterial colonization of the gut is a fundamental requirement for the development and activation of the gut-associated lymphoid tissue.[20],[21] Such colonization is associated with an increase in the number of immunocompetent cells (B-cell, T-cells, and dendritic cells). The complex mutually beneficial interaction between the gut microbiota and the host results in several immunological responses that ensure a dynamic equilibrium between the two partners. Typical examples of such responses include immunoglobulin A secretion and the release of antimicrobial peptides.

Gut-brain axis

Gut microbiota regulate mood and behavior of the host. The brain is able to sense gut bacteria (gutbrain axis). The vagus is thought to play a key role in this bidirectional flow of information.[22]

Control of appetite

There is a complex interaction of genetic, environmental, and behavioral factors in the pathogenesis of obesity.[23] Control of appetite is another function of gut microbiota. Dietary fiber has a complex structure and thus resists digestion in the upper gut, reaches the colon where it is fermented to release SCFAs. Some SCFAs can stimulate the release of appetite-suppressing hormones glucagon-like peptide-1 and peptide YY. Domestic and industrial food processing distorts food structure, leading to the production of energy-dense, more digestible, and easily absorbable products in the upper part of the gut. Bacterial fermentation is thus reduced with attendant loss of benefits derived therefrom.


  Gut Microbiota in Disease Top


The factors that affect the density and diversity of gut microbiota are multiple, including mode of delivery, feeding methods, especially in infancy, level of nutrition, age, diet, drugs, living arrangements, and host immunization.[24],[25],[26],[27],[28],[29] The processes involved are complicated. For instance, the process of aging is associated with a reduction in the propensity of gut microbiota to produce SCFAs with consequent reduction in amylolytic capability of the host. This state may in turn promote inflammatory changes in the gut.[30],[31]

Dysbiosis is associated with a wide range of changes in the health of the host. These changes are underpinned by changes in energy absorption and changes in microbial metabolites such as choline, SCFAs, bile acids, and disturbance of the gutbrain axis.

A proinflammatory state in the gut can be induced by a permanent change in the composition or function of gut microbiota which in turn leads to alteration in intestinal permeability, visceral hypersensitivity, intestinal motility, and alteration in immune and metabolic functions with the potential of initiating certain diseases such as diabetes mellitus, obesity, neurodegenerative and autoimmune diseases.[32],[33]

Although it is difficult to prove causation for many diseases in which gut microbiota plays a role, a number of epidemiological studies have revealed that a reduction in the diversity of gut microbiota is associated with some diseases, including NAFLD, asthma and inflammatory diseases, diabetes and obesity, allergies, inflammatory bowel disease, and irritable bowel syndrome.[34],[35],[36],[37],[38],[39] Others include autism, cancer, anxiety, and depression.[40],[41],[42]


  Therapeutic Applications Top


A reliable approach to the management of diseases related to gut microbiota is to restore the individual from the dysbiotic state to a healthy gut microbiota.[43] The most rational therapeutic options include antibiotics, prebiotics, probiotics, and fecal microbiota transplantation (FMT). FMT has been satisfactorily proven to be efficacious in the management of recurrent  Clostridium difficile Scientific Name Search ection (CDI). The use of FMT in this condition is associated with about 90% therapeutic success and a very good safety profile.[44] Efficacy of FMT in other diseases remains to be established. Protocol standardization for each disease and rigorous evaluation of gut microbiota profile of donors and recipients are variables that will most likely improve outcomes.

The gut microbiome holds promise as an exciting new target for interventions that are diet-based. Accurate glucose response prediction to specific diets is possible through the use of personal and microbiome features.[45] This was made possible through the use of a machine-learning algorithm that integrates blood parameters, dietary habits, anthropometrics, physical activity, and gut microbiota measured in a cohort. The result was an accurate postprandial glycemic response to real-life meals.

The overarching place of gut microbiota in human disease was brought to the fore recently in a seminal viewpoint expressed by Finlay who proposed the hypothesis that diseases that were hitherto classified as noncommunicable, that cannot be transmitted from person to person might actually be transmissible.[46] Conventionally, these noncommunicable diseases (NCDs) are thought to be propagated by genetic, lifestyle, and environmental factors, rather than microbial involvement. Examples include hypertension, diabetes mellitus, obesity, and cancer. Dysbiosis is an underlying factor in these NCDs and in animal experiments, transplantation of the abnormal microbiota of NCD models into healthy animals results in disease in the recipient. Based on this observation, it is plausible to posit that NCDs could have a microbial component, which in this case is the microbiota. In support of this is the fact that people who live together such as spouses tend to have similar microbiota.[47] However, the confounding effect of diet and other environmental factors remains a formidable research frontier.

Gut microbiota, together with new generation sequencing and omics technologies are an emerging flagship in the prevention, diagnosis, and treatment of a wide range of human diseases. However, many questions remain unanswered. The concept of “good” and “bad” gut microbiome remains elusive. It has been difficult to classify these microbiota-driven disorders, and screening methods for recognition of affected persons are yet to be developed. Furthermore, the question of the chicken and the egg is also being re-enacted in this complex relationship. Is dysbiosis the cause or effect of the disease with which it is associated? Answers to these pertinent questions are likely to become available as more results of mechanistic research become available.


  Conclusion Top


The human gut microbiota is a complex colony of diverse micro-organisms whose role in the maintenance of healthy living and causation of a wide range of diseases has become an interesting field of medical research. In health, the microbiota has a unique density and diversity, through which it is able to perform certain metabolic, nutritional, structural, and immunological functions. Perturbations of this uniqueness result in disease. Microbial replacement therapies rely on the deliberate manipulation of this milieu to restore balance. To date, FMT for the treatment of recurrent CDI is the only condition in which microbiome replacement therapy has recorded significant efficacy. Granted that many questions arising from the intricate nature of this subject remain unanswered, the surge in research output in the field confers on gut microbiota an overarching status in disease prevention, diagnosis, and treatment.



 
  References Top

1.
Bäckhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI. Host-bacterial mutualism in the human intestine. Science 2005;307:1915-20.  Back to cited text no. 1
    
2.
Ianiro G, Molina-Infante J, Gasbarrini A. Gastric microbiota. Helicobacter 2015;20 Suppl 1:68-71.  Back to cited text no. 2
    
3.
Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI. The human microbiome project. Nature 2007;449:804-10.  Back to cited text no. 3
    
4.
Belenguer A, Holtrop G, Duncan SH, Anderson SE, Calder AG, Flint HJ, et al. Rates of production and utilization of lactate by microbial communities from the human colon. FEMS Microbiol Ecol 2011;77:107-19.  Back to cited text no. 4
    
5.
Dave M, Higgins PD, Middha S, Rioux KP. The human gut microbiome: Current knowledge, challenges, and future directions. Transl Res 2012;160:246-57.  Back to cited text no. 5
    
6.
Robles-Alonso V, Guarner F. Progress in the knowledge of the intestinal human microbiota. Nutr Hosp 2013;28:553-7.  Back to cited text no. 6
    
7.
Blaser MJ. The microbiome revolution. J Clin Invest 2014;124:4162-5.  Back to cited text no. 7
    
8.
Tang WH, Li DY, Hazen SL. Dietary metabolism, the gut microbiome, and heart failure. Nat Rev Cardiol 2019;16:137-54.  Back to cited text no. 8
    
9.
Hamer HM, Jonkers D, Venema K, Vanhoutvin S, Troost FJ, Brummer RJ. Review article: The role of butyrate on colonic function. Aliment Pharmacol Ther 2008;27:104-19.  Back to cited text no. 9
    
10.
Wong JM, de Souza R, Kendall CW, Emam A, Jenkins DJ. Colonic health: Fermentation and short chain fatty acids. J Clin Gastroenterol 2006;40:235-43.  Back to cited text no. 10
    
11.
David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 2014;505:559-63.  Back to cited text no. 11
    
12.
Kaji I, Karaki S, Kuwahara A. Short-chain fatty acid receptor and its contribution to glucagon-like peptide-1 release. Digestion 2014;89:31-6.  Back to cited text no. 12
    
13.
Chambers ES, Morrison DJ, Frost G. Control of appetite and energy intake by SCFA: What are the potential underlying mechanisms? Proc Nutr Soc 2015;74:328-36.  Back to cited text no. 13
    
14.
Corrêa-Oliveira R, Fachi JL, Vieira A, Sato FT, Vinolo MA. Regulation of immune cell function by short-chain fatty acids. Clin Transl Immunology 2016;5:e73.  Back to cited text no. 14
    
15.
Ghazalpour A, Cespedes I, Bennett BJ, Allayee H. Expanding role of gut microbiota in lipid metabolism. Curr Opin Lipidol 2016;27:141-7.  Back to cited text no. 15
    
16.
Zhao L, Zhang F, Ding X, Wu G, Lam YY, Wang X, et al. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science 2018;359:1151-6.  Back to cited text no. 16
    
17.
Lin HV, Frassetto A, Kowalik EJ Jr., Nawrocki AR, Lu MM, Kosinski JR, et al. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS One 2012;7:e35240.  Back to cited text no. 17
    
18.
Hooper LV. Do symbiotic bacteria subvert host immunity? Nat Rev Microbiol 2009;7:367-74.  Back to cited text no. 18
    
19.
Salzman NH, Underwood MA, Bevins CL. Paneth cells, defensins, and the commensal microbiota: A hypothesis on intimate interplay at the intestinal mucosa. Semin Immunol 2007;19:70-83.  Back to cited text no. 19
    
20.
Mondot S, de Wouters T, Doré J, Lepage P. The human gut microbiome and its dysfunctions. Dig Dis 2013;31:278-85.  Back to cited text no. 20
    
21.
Sommer F, Bäckhed F. The gut microbiota—masters of host development and physiology. Nat Rev Microbiol 2013;11:227-38.  Back to cited text no. 21
    
22.
Collins SM, Bercik P. The relationship between intestinal microbiota and the central nervous system in normal gastrointestinal function and disease. Gastroenterology 2009;136:2003-14.  Back to cited text no. 22
    
23.
Selassie M, Sinha AC. The epidemiology and aetiology of obesity: A global challenge. Best Pract Res Clin Anaesthesiol 2011;25:1-9.  Back to cited text no. 23
    
24.
Yu ZT, Chen C, Kling DE, Liu B, McCoy JM, Merighi M, et al. The principal fucosylated oligosaccharides of human milk exhibit prebiotic properties on cultured infant microbiota. Glycobiology 2013;23:169-77.  Back to cited text no. 24
    
25.
Marcobal A, Barboza M, Sonnenburg ED, Pudlo N, Martens EC, Desai P, et al. Bacteroides in the infant gut consume milk oligosaccharides via mucus-utilization pathways. Cell Host Microbe 2011;10:507-14.  Back to cited text no. 25
    
26.
Bezirtzoglou E, Tsiotsias A, Welling GM. Microbiota profile in feces of breast-and formula-fed newborns by using fluorescence insitu hybridization (FISH). Anaerobe 2011;17:478-82.  Back to cited text no. 26
    
27.
Penders J, Thijs C, Vink C, Stelma FF, Snijders B, Kummeling B, et al. Factors influencing the composition of the intestinal microbiota in early infancy. Pediatrics 2006;118:511-21.  Back to cited text no. 27
    
28.
Favier CF, Vaughan EE, De Vos WM, Akkermans AD. Molecular monitoring of succession of bacterial communities in human neonates. Appl Environ Microbiol 2002;68:219-26.  Back to cited text no. 28
    
29.
Kau AL, Planer JD, Liu J, Rao S, Yatsunenko T, Trehan I, et al. Functional characterization of IgA-targeted bacterial taxa from undernourished Malawian children that produce diet-dependent enteropathy. Sci Transl Med 2015;7:276ra24.  Back to cited text no. 29
    
30.
Woodmansey EJ, McMurdo ME, Macfarlane GT, Macfarlane S. Comparison of compositions and metabolic activities of fecal microbiotas in young adults and in antibiotic-treated and non-antibiotic-treated elderly subjects. Appl Environ Microbiol 2004;70:6113-22.  Back to cited text no. 30
    
31.
Biagi E, Candela M, Turroni S, Garagnani P, Franceschi C, Brigidi P. Ageing and gut microbes: Perspectives for health maintenance and longevity. Pharmacol Res 2013;69:11-20.  Back to cited text no. 31
    
32.
Lynch SV, Pedersen O. The human intestinal microbiome in health and disease. N Engl J Med 2016;375:2369-79.  Back to cited text no. 32
    
33.
Saavedra JM, Dattilo AM. Early development of intestinal microbiota: Implications for future health. Gastroenterol Clin North Am 2012;41:717-31.  Back to cited text no. 33
    
34.
Aron-Wisnewsky J, Gaborit B, Dutour A, Clement K. Gut microbiota and non-alcoholic fatty liver disease: New insights. Clin Microbiol Infec 2013;19:338-48.  Back to cited text no. 34
    
35.
Abrahamsson TR, Jakobsson HE, Andersson AF, Björkstén B, Engstrand L, Jenmalm MC. Low gut microbiota diversity in early infancy precedes asthma at school age. Clin Exp Allergy 2014;44:842-50.  Back to cited text no. 35
    
36.
Everard A, Cani PD. Diabetes, obesity and gut microbiota. Best Pract Res Clin Gastroenterolo 2013;27:73-83.  Back to cited text no. 36
    
37.
Bisgaard H, Li N, Bonnelykke K, Chawes BL, Skov T, Paludan-Muller G, et al. Reduced diversity of the intestinal microbiota during infancy is associated with increased risk of allergic disease at school age. J Allergy Clin Immunol 2011;128:646-52.  Back to cited text no. 37
    
38.
Holleran G, Lopetuso LR, Ianiro G, Pecere S, Pizzoferrato M, Petito V, et al. Gut microbiota and inflammatory bowel disease: So far so gut! Minerva Gastroenterol Dietol 2017;63:373-84.  Back to cited text no. 38
    
39.
Kennedy PJ, Cryan JF, Dinan TG, Clarke G. Irritable bowel syndrome: A microbiome-gut-brain axis disorder? World J Gastroenterol 2014;20:14105-25.  Back to cited text no. 39
    
40.
Iebba V, Aloi M, Civitelli F, Cucchiara S. Gut microbiota and pediatric disease. Dig Dis 2011;29:531-9.  Back to cited text no. 40
    
41.
Cammarota G, Ianiro G, Ahern A, Carbone C, Temko A, Claesson MJ, et al. Gut microbiome, big data and machine learning to promote precision medicine for cancer. Nat Rev Gastroenterol Hepatol 2020;17:635-48.  Back to cited text no. 41
    
42.
Lach G, Schellekens H, Dinan TG, Cryan JF. Anxiety, depression, and the microbiome: A role for gut peptides. Neurotherapeutics 2018;15:36-59.  Back to cited text no. 42
    
43.
Ianiro G, Bibbò S, Gasbarrini A, Cammarota G. Therapeutic modulation of gut microbiota: Current clinical applications and future perspectives. Curr Drug Targets 2014;15:762-70.  Back to cited text no. 43
    
44.
Ianiro G, Valerio L, Pecere S, Bibbo S, Quaranta G, Posteraro B, et al. Predictors of failure after single fecal microbiota transplantation in patients with recurrent Clostridium difficile infection: Results from a 3-year, single center cohort study. Clin Microbiol Infect 2017;23:337.e1-3.  Back to cited text no. 44
    
45.
Zeevi D, Korem T, Zmora N, Israeli D, Rothschild D, Weinberger A, et al. Personalized nutrition by prediction of glycemic responses. Cell 2015;163:1079-94.  Back to cited text no. 45
    
46.
Finlay BB, CIFAR Humans, Microbiome. Are noncommunicable diseases communicable? Science 2020;367:250-1.  Back to cited text no. 46
    
47.
Brito IL, Gurry T, Zhao KH, Young SK, Shea TP, Nasilisili W, et al. Transmission of human-associated microbiota along family and social networks. Nat Microbiol 2019;4:964-71.  Back to cited text no. 47
    




 

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  In this article
Introduction
Physiological Fu...
Gut Microbiota i...
Therapeutic Appl...
Conclusion
References

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