Human Microbiome

"The human microbiome refers specifically to the collective genomes of resident microorganisms." [1] These microorganisms living in humans include a long list, i.e., bacteria, archaea, protists, fungi, helminths, protozoa, virsuses and other microbes. Traditionally, non human microorganisms in the human body have been estimated to be way more than human organisims, depending on what you designate is actually 'human', but more recent estimates put this number at a 50/50 ratio, so, this subject is debated among biologists. [1] Another debate is how many species of microbes are there? [1]

Let's focus first on bacteria, the most studied subject of the human microbiome.

Focus on Bacteria - Bias Toward Other Microbes

It is of interest to note how viruses and other microbes have traditionally been ignored or not included in reports about life on planet earth or in the human microbiome creating a bias toward them. For example, Vox reports about a study in the Proceedings of the National Academy of Sciences about a census sorting all the life on earth by weight with really cool graphics and totally omits virus which we now know outweighs all life on planet earth.

Wikipedia in its article about Global Biomass ignores viruses. However, in its article about Virus, note what Wikipedia states:

"Viruses are by far the most abundant biological entities on Earth and they outnumber all the others put together. They infect all types of cellular life including animals, plants, bacteria and fungi."

"Microorganisms constitute more than 90% of the biomass in the sea. It is estimated that viruses kill approximately 20% of this biomass each day and that there are 10 to 15 times as many viruses in the oceans as there are bacteria and archaea."

Why would the Wikipedia article about Global Biomass ignore virus? This is a typcial bias example toward focusing on bacteria which dominates medical scientific thinking and influences views thus distorting research results with the human microbiome. This bias also exists for other microbes besides virus.

Bacteria

An interesting article published in Scientific American, states, "A new study, published online April 20 in Nature, proposes a simple schematic for profiling people's gut microbiota, breaking down these helpful hangers-on into three overarching categories." [2] This article suggests 'typing' a human microbiome patient into one of three types, similar to blood types, to improve medical treatment and diet. "Because of their small size, however, microorganisms make up only about 1 to 3 percent of the body's mass (in a 200-pound adult, that’s 2 to 6 pounds of bacteria), but play a vital role in human health." [3] As previously mentioned, medical science has focused traditionally on bacteria research and this bias influences the research of other microbes and taints the bigger picture of the human microbiome since bacteria only makes up a small mass of the human microbiome. To see the bigger picture, lets now focus on other microbes that live in humans.

Virus

There are "over 10 million times more viruses than there are stars in the universe." [4] To put this into perspective, "The total number of flu viruses in your body can rise to 100 trillion within a few days. That’s over 10,000 times more viruses than people on Earth." [4] And you thought that the flu shot you took this year might help you? " Viruses are about a thousand times smaller than bacteria, and bacteria are much smaller than most human cells." [5] "Some scientists estimate that there are a hundred times more virus particles than human cells in the human body (and 10 times more viruses than bacteria). " [6] Based upon this figure, that means that the human body contains 10 to 30 percent of the body's mass (in a 200-pound adult, that's 10 to 60 pounds of virus). This corresponds with how viruses out number all the life on planet earth. [Tree of Life] Since virus have such a significant mass in the human microbiome, including the role virus may play in understanding human health and disease is an important focus worth considering in the human microbiome. Bacteriophage are a particular virus that are included in the human microbiome that "have been used for over 90 years as an alternative to antibiotics in the former Soviet Union and Central Europe as well as in France." [6]

Archaea

Archaea exist in the human gut, skin, lung and nose, but little is known about this subject. "Since archaea have been known to be associated with the human gut for several decades, one would think that human microbiome studies may unravel new facets of archaea–human interactions." [7] But alas, little is known about this subject, especially the number or percentage of archaea in the human microbiome, which one source says, "in contrast to the enormous variety of bacteria in this organ [human gut], the numbers of archaeal species are much more limited." [1] Another source states, "“We also recognize that archaea are often not fully assessed even in metagenome-based studies, due to the gaps in databases and the limited number of cultivated reference archaea—in particular from the human microbiome. Much more work is now necessary to assess the full picture of the human microbiome.” [8] Somehow archaea interact with the other microorganisms in the human microbiome and without a doubt effect human health and disease. However, as one publication points out, "Human-associated archaea remain, similar to fungi or viruses, [are] understudied in the field of microbiome research." [9] How much of our human microbiome contains archaea? Most reports say less than bacteria, but do not provide figures. There is no known archaea human pathogen. What the role archea plays in the human microbiome is worth considering since there may be some surprises found in researching archaea.

Fungi

As with virus and archaea little is known about fungi since research has focused primarly on bacteria for the past hundred years or more. Fungi also exist throughout the human microbiome. Athlete’s foot, ringworm, diaper rash, dandruff, some cases of sinusitis, and vaginal yeast infections are all caused by fungi. One NPR report states, "Whereas previous research reported a relatively limited number of fungal species in our oral cavities — primarily Candida, which when overgrown causes thrush – Ghannoum and his colleagues identified a veritable zoo of fungal colonists in the mouths of the 20 study participants." [10] Another report "revealed 80 genera of fungi on the surface of our bodies." Fungi is in a lot of things human eat, from bread to beer. How much fungi does the human body have? One report says "0.1 percent of the population of microbes in our guts." [10] However, that number could change depending on new data. Wikipedia reports, "However, little is known of the true biodiversity of Kingdom Fungi, which has been estimated at 2.2 million to 3.8 million species.[5] Of these, only about 120,000 have been described, with over 8,000 species known to be detrimental to plants and at least 300 that can be pathogenic to humans." [6] Nevertheless, "Fungi are an important part of the microbiome, along with bacteria and viruses." [10]

Protozoa

Protozoa, usually viewed as parasites, are included in the human microbiome, particularly in the gut. As one paper on this subject notes, "The human gut microbiota spans the tree of life and includes bacteria, viruses, and eukaryotes such as fungi, helminths, and protozoa. However, our current understanding of the microbiota is heavily biased towards the bacterial component (due to the approach consisting in amplifying the 16S rRNA gene) and is primarily based on findings from industrialized countries, characterized, among other things, by a reduced infectious burden." [11] Plasmodium falciparum (malaria) is a protozoa. Just as there are beneficial bacteria and pathogen bacteria, there is growing evidence that there are beneficial viral microbes as well as pathogen viruses, and the same is true with protozoa. The authors of the same article state, "We argue that protozoa, like helminths, represent an important factor to take into account when studying the gut microbiome, and that their presence - especially considering their long coevolutionary history with humans - may be beneficial." [11] Protozoa not only live in the gut but also in the blood and tissues of humans, i.e., vagina. Protozoa have a bad reputation, since a significant number of deaths due to diarrhea are caused by three protozoas, Entamoeba, Cryptosporidium, and Giardia. [11] Mark F. Wiser, Tulane University, in discussing the protozoa inhabiting the human gut, posts "The majority of these protozoa are non-pathogenic commensals, or only result in mild disease." [11] How protozoa interact and work with or for the human microbiome only time will tell as more data is researched.

Helminths

A significant number of humans on planet earth are infected with helminths (worms) as PloS One points out, "More than 1 billion people worldwide are estimated to be infected by gastrointestinal (GI) soil-transmitted helminths, including the roundworm Ascaris lumbricoides, the whipworm Trichuris trichiura and the hookworms Necator americanus and Ancylostoma duodenale." [12] That is a ratio of 1/7.5 that the human microbiome has helminths, which means you have a 1 in 7 chance helminths are in you. There is a theory that humans have a symbiotic relationship with helminths for a long time, but Western medicine and diet has eradicated these parasites in a significant number of humans in the industrialized world. While normally viewed as parasites, helminths may have a symbiotic beneficial relationship within the human microbiome. In fact, it may be surprising to note that modern medicine has re-introduced helminths as a medical treatment for allergies and gut disorders such as ulcerative colitis with remarkable improvements (BBC News, Eat worms - feel better). [12] Wikipedia reports, "One study suggests a link between the rising rates of metabolic syndrome in the developed worlds and the largely successful efforts of Westerners to eliminate intestinal parasites.....Although sparse in blood of persons in developed countries, eosinophils are often elevated in individuals in rural developing countries where intestinal parasitism is prevalent and metabolic syndrome rare. " [12] One paper suggests, "it is foreseeable that the exploration of parasites, protozoa, and worms within microbiota communities by “omic” technologies may provide more fully comprehensive information on gut prokaryote profiles. Such “omics”-based approaches are built on a holistic vision of the systems analysed, systems in which 'all components are considered in complex ecological networks' in order to provide complete profiles of genes/transcripts/proteins/metabolites." [12] Further research may reveal a better understanding of helminths in the human microbiome.

Demodex

"To date, two of the 0.2–0.4 mm long mite species are known to inhabit human skin. Demodex folliculorum is found in hair follicles in clusters with other mites of the same species. The smaller mite Demodex brevis resides alone in sebaceous glands or in meibomial glands which are located at the rim of the eyelids." [13] What role these mites play on human skin is not known, but some symbiotic relationship may be found. Most humans have no issues with demodex but in some rosacea patients the number of demodex mites are higher than in the normal human population diagnosed as demodectic rosacea. All humans have demodex except for newborn babies. Demodex are an arthropod.

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End Notes

[1] Human microbiota, Wikipedia

More than half your body is not human, James Gallagher, Presenter, The Second Genome, BBC Radio 4, BBC News

Earth May Be Home to a Trillion Species of Microbes, By Nicholas Bakalar, The New York Times, May 23, 2016

After All, Only Millions?, Rudolf Amann, Ramon Rosselló-Móra, DOI: 10.1128/mBio.00999-16, American Society for Microbiology

One report says the ratio of non human microbes to human cells is a ratio of 1.3:1.

How Much Bacteria Does The Human Body Really Contain?, IFL Science

[2] What's in your gut? Microbiota categories might help simplify personalized medicine, Katherine Harmon, April 20, 2011, Scientific American

[3] NIH Human Microbiome Project defines normal bacterial makeup of the body, NIH

An article reports that 43% of the human body are made up of human cells and gives this quote, " 'The remaining 57 percent are bacteria, fungi and single-celled eukaryotes that live in our guts, in our mouths, on our skins, and in the female reproductive tract,' says Sarkis Mazmanian, a microbiology researcher at Caltech."

ONLY 43% OF OUR BODIES ARE MADE UP OF HUMAN CELLS… SO WHAT’S THE OTHER 57%?, Andrew Fiouzi, Mel Magazine

[4] An Infinity of Viruses, Carl Zimmer, The Loom, National Geographic

[5] Viruses: One of Human's Strongest Enemies, Jason Lavender, Duke University, Taking Africa a Step Ahead, MIT

[6] Globe-Trotting Virus Hides Inside People's Gut Bacteria, Michaeleen Doucleff, Goats and Soda, NPR

One article on global biomass discusses the uncertaintiy of obtaining figures for this and states, "Global biomass estimates vary in the amount of information they are based on and, consequently, in their uncertainty." As for virus, this same article states, "We supplement these kingdoms of living organisms with an estimate for the global biomass of viruses, which are not included in the current tree of life but play a key role in global biogeochemical cycles." Figure 1 shows a smaller mass for viruses than for bacteria, archaea and fungi.

The biomass distribution on Earth, Yinon M. Bar-On, Rob Phillips, and Ron Milo

PNAS June 19, 2018 115 (25) 6506-6511; published ahead of print May 21, 2018 https://doi.org/10.1073/pnas.1711842115

Bacteriophage, Wikipedia

[7] PLoS Pathog. 2015 Jun; 11(6): e1004833. Published online 2015 Jun 11. doi: 10.1371/journal.ppat.1004833

Archaea in and on the Human Body: Health Implications and Future Directions, Mor N. Lurie-Weinberger and Uri Gophna, Joseph Heitman, Editor

[8] New Insight into Archaeal Members of the Human Microbiome, Julie Wolf, American Society for Microbiology

[9] First Insights into the Diverse Human Archaeome: Specific Detection of Archaea in the Gastrointestinal Tract, Lung, and Nose and on Skin

Kaisa Koskinen, Manuela R. Pausan, Alexandra K. Perras, Michael Beck, Corinna Bang, Maximilian Mora, Anke Schilhabel, Ruth Schmitz, Christine Moissl-Eichinger

Christa M. Schleper, Invited Editor, Janet K. Jansson, Editor, American Society for Microbiology

[10] The Human Body's Complicated Relationship With Fungi, Bret Stetka, NPR

"0.1 percent of the population of microbes in our guts."

There are fungi living inside your gut, and they're probably pretty important, Claire Maldarelli October 12, 2017, Popular Science

"revealed 80 genera of fungi on the surface of our bodies.

Yes, It’s True: There’s Fungus Among Us, Dr. Francis Collins, May 28th, 2013, NIH Director's Blog

"Fungi are an important part of the microbiome, along with bacteria and viruses."

Getting To Know Your Inner Mushroom, Carl Zimmer, National Geographic

[11] Gut Protozoa: Friends or Foes of the Human Gut Microbiota?

Magali Chabé, Ana Lokmer, Laure Ségurel, OPINION| VOLUME 33, ISSUE 12, P925-934, DECEMBER 01, 2017, PubMed

In 2010, an estimated 357 million cases of illness with at least one of three enteric protozoa, Entamoeba, Cryptosporidium, and Giardia, resulted in 33,900 deaths and the loss of 2.94 million disability-adjusted life years (12).

Parasitic Protozoa and Interactions with the Host Intestinal Microbiota

Stacey L. Burgess, Carol A. Gilchrist, Tucker C. Lynn, William A. Petri, Jr., Anthony T. Maurelli, Editor

"The majority of these protozoa are non-pathogenic commensals, or only result in mild disease.", Mark F. Wiser, Tulane University

[12] PLoS One. 2017; 12(9): e0184719.

Infections by human gastrointestinal helminths are associated with changes in faecal microbiota diversity and composition

BBC News, Eat worms - feel better, December 3, 2003

Parasitic worm (Redirected from Helminths), Wikipedia

“Omic” investigations of protozoa and worms for a deeper understanding of the human gut “parasitome”

Valeria Marzano, Livia Mancinelli, Giorgia Bracaglia, Federica Del Chierico, Pamela Vernocchi, Francesco Di Girolamo, Stefano Garrone, Hyppolite Tchidjou Kuekou, Patrizia D’Argenio, Bruno Dallapiccola, Andrea Urbani, Lorenza Putignani

Published: November 2, 2017https://doi.org/10.1371/journal.pntd.0005916

[13] Trends Microbiol. 2013 Dec; 21(12): 660–668.

Structure and function of the human skin microbiome

Nina N. Schommer and Richard L. Gallo