Human microbiota: definition, composition, functions, antibiotics

CONTENTS

What is the human microbiota?

Human Microbiota
Fig. 1 – Lactobacillus casei

It has been known for almost a century that humans harbor a microbial ecosystem, known as human microbiota, remarkably dense and diverse, made up of a  number of viruses and cells much higher than those of the human body, and that accounts for one to three percent of body weight. All the genes encoded by the human body’s microbial ecosystem, which are about 1,000 times more numerous than those of our genome, make up the human microbiome. Microorganisms colonize all the surfaces of the body that are exposed to the environment. Indeed, distinct microbial communities are found on the skin, in the vagina, in the respiratory tract, and along the whole intestinal tract, from the mouth up to rectum, the last part of the intestine.

Composition of the human microbiota

It is composed of organisms from all taxa.

  • Bacteria, at least 100 trillion (1014) cells, a number ten times greater than that of the human body. They are found in very high concentration in the intestinal tract, up to 1012-1014/gram of tissue, where they form one of the most densely populated microbial habitats on Earth. In the gut, bacteria mainly belong to the Firmicutes, Bacteroidetes and Actinobacteria phyla. Fusobacteria (oropharynx), Tenericutes, Proteobacteria, and Verrucomicrobia are other phyla present in our body.
    Note: Bacterial communities in a given body region resemble themselves much more across individuals than those from different body regions of the same individual; for example, bacterial communities of the upper respiratory tract are much more similar across individuals than those of the skin or intestine of the same individual.
  • Viruses, by far the most numerous organisms, about quadrillion units. The genomes of all the viruses harbored in the human body make up the human virome. In the past, viruses and eukaryotes (see below) have been studied focusing on pathogenic microorganisms, but in recent years the attention has also shifted on many non-pathogenic members of these groups. And many of the viral gene sequences found are new, which suggests that there is still much to learn about the human virome. Finally, just like for bacteria, there is considerable interpersonal variability.
  • Archaebacteria, primarily those belonging to the order Methanobacteriales, with Methanobrevibacter smithii predominant in the human gut (up to 10% of all anaerobes).
  • Eukaryotes, and the parasites of the genera Giardia and Entamoeba have probably been among the first to be identified. But there is also a great abundance and diversity of fungal species, belonging to genera such as Candida, Penicillium, Aspergillus, Hemispora, Fusarium, Geotrichum, Hormodendrum, Cryptococcus, Saccharomyces, and Blastocystis.
Human Microbiota
Fig. 2 – Candida albicans

Based on the relationships with the human host, microorganisms may be classified as commensals or pathogens.

  • Commensals cause no harm to the host, with which they establish a symbiotic relationship that generally brings benefits to both.
  • On the contrary, pathogens are able to cause diseases, but fortunately represent a small percentage of the human microbiota. These microorganisms establish a symbiosis with the human host and benefit from it at the expense of the host. They can cause disease:

if they move from their niche, such as the intestine, into another one where they do not usually reside, such as the vagina or bladder (as in the case of Candida albicans, normally present in the intestine, but in very small quantities);
in patients with impaired immunological defenses, such as after an immunosuppressive therapy.

Functions of the human microbiota

Human Microbiota
Fig. 3 – Bifidobacterium longum

Sometimes referred to as “the forgotten organ“, human microbiota, mainly with its intestinal bacterial members, plays many important functions that can lead to nutritional, immunological, and developmental benefits, but can also cause diseases. Here are some examples.

  • It is involved in the development of the gastrointestinal system of the newborn, as shown by experiments carried out on germ-free animals in which, for example, the thickness of the intestinal mucosa is thinner than that of colonized animals, therefore more easily subject to rupture.
  • It contributes to energy harvest from nutrients, due to its ability to ferment indigestible carbohydrates, promote the absorption of monosaccharides and the storage of the derived energy. This has probably been a very strong evolutionary force that has played a major role in favor of the fact that these bacteria became our symbionts.
  • It contributes to the maintenance of the acidic pH of the skin and in the colon.
  • It is involved in the metabolism of xenobiotics and several polyphenols.
  • It improves water and mineral absorption in the colon.
  • It increases the speed of intestinal transit, slower in germ-free animals.
  • It has an important role in resistance to colonization by pathogens, primarily in the vagina and gut.
  • It is involved in the biosynthesis of isoprenoids and vitamins through the methylerythritol phosphate pathway.
  • It stimulates angiogenesis.
  • In the intestinal tract, it interacts with the immune system, providing signals for promoting the maturation of immune cells and the normal development of immune functions. And this is perhaps the most important effect of the symbiosis between the human host and microorganisms. Experiments carried out on germ-free animals have shown, for example, that:

macrophages, the cells that engulf pathogens and then present their antigens to the immune system, are found in much smaller amounts than those present in the colonized intestine, and if placed in the presence of bacteria they fail to find and therefore engulf them, unlike macrophages extracted from a colonized intestine;
there is not the chronic non-specific inflammation, present in the normal intestine as a result of the presence of bacteria (and of what we eat).

  • Changes in its composition can contribute to the development of obesity and metabolic syndrome.
  • It protects against the development of type I diabetes.
  • Many diseases, both in children and adults, such as stomach cancer, lymphoma of mucosa-associated lymphoid tissue, necrotizing enterocolitis (an important cause of morbidity and mortality in premature babies) or chronic intestinal diseases, are, and others seem to be, related to the gut microbiota.

In conclusion, it seems very likely that the human body represents a superorganism, result of years of evolution and made up of human cells, and the resulting metabolic and physiological capacities, as well as an additional organ, the microbiota.

Human Microbiome Project

Human Microbiota
Fig. 4 – Human Microbiome Project

The bacterial component of the human microbiota is the subject of most studies including a large-scale project started in 2008 called “Human Microbiome Project“, whose aim is to characterize the microbiome associated with multiple body sites, such as the skin, mouth, nose, vagina and intestine, in 242 healthy adults. These studies have shown a great variability in the composition of the human microbiota; for example, twins share less than 50% of their bacterial taxa at the species level, and an even smaller percentage of viruses. The factors that shape the composition of bacterial communities begin to be understood: for example, the genetic characteristics of the host play an important, although this is not true for the viral community. And metagenomic studies have shown that, despite the great interpersonal variability in microbial community composition, there is a core of shared genes encoding signaling and metabolic pathways. It appears namely that the assembly and the structure of the microbial community does not occur according to the species but the more functional set of genes. Therefore, disease states of these communities might be better identified by atypical distribution of functional classes of genes.

Effects of antibiotics

Clostridium
Fig. 5 – Clostridium difficile

The microbiota in healthy adult humans is generally stable over time. However, its composition can be altered by factors such as dietary changes, urbanization, travel, and especially the use of broad-spectrum antibiotics. Here are some examples of the effects of antibiotic treatments.

  • There is a long-term reduction in microbial diversity.
  • The taxa affected vary from individual to individual (even up to a third of the taxa).
  • Several taxa do not recover even after 6 months from treatment.
  • Once the bacterial communities have reshaped, a reduced resistance to colonization occurs. This allows foreign and/or pathogen bacteria, able to grow more than the commensals, to cause permanent changes in human microbiota structure, as well as acute diseases, such as the dangerous pseudomembranous colitis, and chronic diseases, as it is suspected for asthma following the use and abuse of antibiotics in childhood. Moreover, their repeated use has been suggested to increase the pool of antibiotic-resistance genes in our microbiome. In support of this hypothesis, a decrease in the number of antibiotic-resistant pathogens has been observed in some European countries following the reduction in the number of antibiotics prescribed.

Finally, you must not underestimate the fact that the intestinal microflora is involved in many chemical transformations, and its alteration could be implicated in the development of cancer and obesity. However, regarding use of antibiotics, you should be underlined that if western population has a life expectancy higher than in the past is also because you do not die of infectious diseases!

References

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Clemente J.C., Ursell L.K., Wegener Parfrey L., and Knight R. The impact of the gut microbiota on human health: an integrative view. Cell 2012;148:1258-70. doi:10.1016/j.cell.2012.01.035

Gill S.R., Pop M., Deboy R.T., Eckburg P.B., Turnbaugh P.J., Samuel B.S., Gordon J.I., Relman D.A., Fraser-Liggett C.M., and Nelson K.E. Metagenomic analysis of the human distal gut microbiome. Science 2006;312:1355-59. doi:10.1126/science.1124234

Palmer C., Bik E.M., DiGiulio D.B., Relman D.A., and Brown P.O. Development of the human infant intestinal microbiota. PLoS Biol 2007;5(7):e177. doi:10.1371/journal.pbio.0050177

The Human Microbiome  Project

Turnbaugh P.J., Gordon J.I. The core gut microbiome, energy balance and obesity. J Physiol 2009;587:4153-58. doi:10.1113/jphysiol.2009.174136

Zhang, T., Breitbart, M., Lee, W., Run, J.-Q., Wei, C., Soh, S., Hibberd, M., Liu, E., Rohwer, F., Ruan, Y. Prevalence of plant viruses in the RNA viral community of human feces. PLoS Biol 2006;4(1):e3. doi:10.1371/journal.pbio.0040003

Published by Dr. Nicola Tazzini

Nicola Tazzini, MS in Biology Sciences Doctor Tazzini graduated "Summa cum Laude" at the University of Pisa on Nov. 11th, 1996 after 1½ year, carried out in the laboratory of Biochemistry of the Department of Biochemistry and Physiology of the Faculty of Natural, Physical and Mathematical Sciences. The subject of his thesis was "Studies about the mechanism of cytotoxicity of the combination of deoxyadenosine and deoxycoformicine on a cell line derived from a human colon carcinoma" (see References). He registered as a Biologist at the University of Pisa on May 10th, 1998. He specialized "Summa cum Laude" in "Biochemistry and Clinical Chemistry" in Oct. 30th, 2001 at the Department of Biological Chemistry of the Faculty of Medicine and Surgery of the University of Parma. The subject of his thesis was: "Analyses of ematochemical, enzymatic and non-enzymatic parameters with antioxidant activity in young professional athletes". He has started his activity of Nutritionist on Feb. 02nd, 2002. He attended the following courses related to the activity of Nutritionist. 2000 1. Pasta in human nutrition. Associazione Biologi Nutrizionisti Italiani. 2. Course of forming and updating in nutrition and health: roll of Biologist. Associazione Scientifica Biologi Pisa. 2001 1. Elements of nutrition. Associazione Scientifica Biologi Pisa. 2002 1. Nutrition as healthy factors, professional update. Associazione Biologi Nutrizionisti Italiani. 2003 1. Nutrition as healthy factors- first part. Associazione Biologi Nutrizionisti Italiani. 2004 1. Nutrition as healthy factors- second part. Associazione Biologi Nutrizionisti Italiani. 2. Nutrition in childhood. Associazione Biologi Nutrizionisti Italiani. 3. Sport activity, growth and correct nutrition. Associazione Biologi Nutrizionisti Italiani. 4. Nutrition and tumor. PLANNING congressi Srl. 2005 1. Doping: guidelines and diagnostic assessments: legal, biochemical, medical and toxicological aspects. Restless Architech of Human Possibilities S.a.s. 2. Nutrition in the third age: nutritional issues and proper nutritional habits. Associazione Biologi Nutrizionisti Italiani. 3. Technical legislation evolution and ethics in development of the profession. Ordine Nazionale dei Biologi. 2006 1. Sport and nutrition. Syntonie S.r.l. 2. Nutrition and prevention: choose to stay healthy. Ordine Nazionale dei Biologi. 3. Pathology nutrition and legislation aspects. Syntonie S.r.l. 4. Nutrition: guidelines. Ordine Nazionale dei Biologi. 2007 1. Nutrition topics: food as welfare tool: physiological and pathological balance factors. Ordine Nazionale dei Biologi. 2008 1. Outdoor and indoor environment. Resources and balances. Ordine Nazionale dei Biologi. 2. Biologist ’profession in the current technical legislation evolution. Ordine Nazionale dei Biologi. 3. Prevention of childhood obesity: nutritional strategies from pregnancy to school age. Ordine Nazionale dei Biologi. 2009 1. Nutrition, the cornerstone. Nutritional and health needs in the era of the genome. S.I.N.U. 2010 1. The evolution of food safety. Ordine Nazionale dei Biologi. 2. Food safety and correct nutrition. Associazione Scientifica Biologi Pisa and Ordine Nazionale dei Biologi. 2011 1. Role of coffee in physiological and pathological states. CMGRP Italia S.p.A. Reference 1. Bemi V., Tazzini N., Banditelli S., Giorgelli F., Pesi R., Turchi G., Mattana A., Sgarrella F., Tozzi M.G., Camici M. Deoxyadenosine metabolism in a human colon-carcinoma cell line (LoVo) in relation to its cytotoxic effect in combination with deoxycoformycin. Int J Cancer 1998;75(5):713-20. doi:https://doi.org/10.1002/(SICI)1097-0215(19980302)75:53.0.CO;2-1 2. Cassandra Studio . Nutraceuti e cibi funzionali. Youcanprint, 2015 3. Singh A.N., Baruah M.M. & Sharma N. Structure based docking studies towards exploring potential anti-androgen activity of selected phytochemicals against prostate cancer. Sci Rep 2017;7(1):1955. doi:10.1038/s41598-017-02023-5 4. Wee T.T., Lun K.R. Teaching science in culturally relevant ways: ideas from Singapore teachers. World Scientific, 2014

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