„Invisible helpers”, that’s how we can call trillions of microscopic organisms, too small to be seen by the human eye, living in our organism. In fact, our own cells do not make even a half of the overall number of cells forming our bodies. We are huge ecosystems and home for variety of microbes, such as bacteria, archaea, protists, viruses or fungi. The truth is that there are around 100 trillion microbial cells and only 10 trillion our own human cells making up our body . Unfortunately, the society used to think of microbes in our organism in a negative way, probably due to the rapidly spreading information and news about the diseases caused by them . However the reality is that the large number of these microbes help us enourmously, with their presence being essential for human health and homeostasis . They live in various parts of our body, such as skin, mouth or gut, choosing niches according to their preference1 – Fig. 13. In this essay there will be a tour around the human body and it’s microbiome to show the positive impact and contribution to our health provided by the microorganisms living ‘within us’.
Skin
We start our journey around the beneficial microflora of the organism on the largest organ in our body , the skin. It’s not a secret that our skin is a home to billions of microorganisms. It actually hosts more than 500 different species of bacteria . The microorganisms that give us benefits are the commensal microbes. Commensal microbes defend the skin and prevent many infections . One of them is the Bacillus subtilis, a bacteria living on our skin and producing bacitracin3, a mixture of related cyclic polypeptides that stop the growth of pathogenic bacteria . Another good example of a microorganism that is our natural protector will be the commensal skin bacteria Staphylococcus epidermidis which inhibit the process of colonization and biofilm formation by a pathogenic microorganism Staphylococcus aureus . Staphylococcus epidermidis produce the endopeptitase and bacteriocins - antibacterial peptides that inhibit the growth of similar or closely related bacterial strains . That mechanism works as a defence against the colonization of S. aureus. Moreover, S. epidermidis trigger keratinocyte expression of antimicrobial peptides and produce the lipotechoic acid in the cel wall as this is a Gram-positive bacteria. The Lipoteichoic acid activates a toll-like receptor 2 (TLR2) in a mast cell of a human skin and this way elicits the release of the cathelicidin (another antimicrobial peptide). That mechanism is actually very helpful, becuse it increases the ability of our mast cells to prevent the infection caused by the pathogenes, such as Vaccinia Virus (VV), when the epithelium is damaged . In addition, Staphylococcus epidermidis are present in the nasal cavities, which corresponds with the decreased chance of getting an infection caused by the Staphylococcus aureus . Therefore, this poses a question, whether Staphylococcus epidermidis aren’t actually more symbiotic than commensal microorganisms due to their beneficial role.
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Oral cavity
Let’s move down from our nasal cavity to our mouth. It’s found out that our oral microbiome is not only pointwise beneficial (as it was in case of S. epidermidis), but also have a positive impact on more than a one system in our body, for example on the circulatory system. The oral bacteria, facilitate the formation of nitrite, an intermediate in the bioactivation of inorganic nitrate. The nitrate is accumulated in saliva, being firstly ingested and absorbed. This hapens due to the active transport from blood to the salivary glands. The nitrite produced with the participation of the oral microorganisms contributes to the increase of the nitrite levels within the blood and tissues. The elevation of the circulating nitrite levels is followed by further reduction of nitrite to NO and other bioactive nitrogen oxides. That nitrogen oxide acts as a vasodilator, affecting the smooth muscles in the blood vessels, preventing them from tightening and the vessel walls from narrowing . That process reduces blood pressure as a result. However, besides that, nitrogen oxide can have many other potentially adventageous roles, such as inhibiting the platelet aggregation or making the mitochondrial processes more efficient .
Apart from having a positive impact on our circulatory system, the oral microbiome plays the important role in supporting the immune defence. Microorganisms living in our mouth prevent the progression of many diseases caused by pathogenes. Bacteria can colonize two types of surfaces within our oral cavity, one of them is the oral mucosa (the mucous membrane of the oral cavity) and the second is the enamel surface on our teeth. Both of them provide the suitable environment and conditions for the communities of microorganisms to thrive. However, distinct microbes have a tendency to choose different niches according to their preference of diverse surface function or structure. Populations of microbes tend to chose niches that provide them with suitable nutrients and conditions. Our domesticated bacteria in the oral cavities occupy the niche preferred by a pathogens, ipso facto, preventing the pathogens from adhering onto specific surfaces . In addition, there is evidence that our domesticated oral microorganisms have the ability to degrade the pathogen’s virulence factors, which help bacteria to invade the host, cause disease and evade host defenses. These factors include adherence and invasion factors, capsule, endo- and exotoxins and siderophores .
But this is not the end of the beneficial properties of our oral microbiome. One of the first colonizers of the human oral cavity and gut after birth , Streptococcus salivarius, in known to diminish the frequency of the colonization of the pathogens infecting the upper respiratory tract. Streptococcus salivarius (strain K12) is also known as BLIS – bacteriocitin-like inhibitory substance K12, owes its name to the ability to release efficiently two lantibiotic bacteriocitins (salivaricin A2 and salivaricin B). Thanks to this property, that strain of Streptococcus salivarius is able to inhibit the growth of (group A) Streptococcus pyogenes and consequently reduce the chance of getting pharyngitis, tonsillitis or acute otitis media by the host. Apart from counteracting the growth of Streptococcus pyogenes, Streptococcus salivarius can also act against many different potential pathogens that are the cause of halitosis and acute otitis media, including Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Micrococcus luteus, Streptococcus anginosus, Eubacterium saburreum, and Micromonas micros . Streptococcus salivarius K12 can be isolated from the saliva of a healthy child and is used as a probiotic for the oral cavity, thanks to its antimicrobial properties .
Intestines
Moving downwards our organism, we look at the beneficial role of the microorganisms living in our digestive system. The gut microbiota have many important functions, such as protective, immunomodulatory, metabolic and trophic roles. The protective role is performed by the domesticated microbiome living in the intestine. They prevent the infection by resisting the colonization of invasive microbes, including Clostridium difficile and Helicobacter pylori . This function is called the colonization resistance. Some bacteria (adherent nonpathogenic) contribute to it by preventing the pathogens from attaching and entering the epithalial cells. Also commensal bacteria by competing for resources and ecological niches, manage and consume all available nutrients that could be pontentially used by pathogens .
The commensal bacteria play an important role in the host immune system counteracting the development of a disease. Microbes influence the differentiation of T cell populations that can be educated, among others, by the commensal microbiota . Commensal microorganisms are associated with development of T helper (Th1, Th2, Th17) cells .
The intestinal microbiome contributes to the nutritional status of the host due to its ability to sythesise particular vitamins19. Bacillus subtilis is a bacteria living in the gastrointestinal tract of humans, that is known to synthesize pyridoxal 5′-phosphate (PLP), which is the biologically active form of vitamin B6. There is evidence that PLP is a necessery cofactor for many metabolic enzymes .
However, in the distal intestine there are more bacteria species that actually synthesize vitamins, including thiamine, folate, biotin, riboflavin and panthothenic acid. Interestingly, the gut bacteria (such as Bacteroides fragilis and Escherichia coli ) provide us with up to half of the daily Vitamin K requirement . Vitamin K is naturally occuring in two different forms. Vitamin K1, named phylloquinone (PK) and vitamin K2, called menaquinone (MK). Menaquinone is the one that is synthesized by our gut microbiota and plays the main role in the metabolism of calcium, a key mineral for the formation and maintenance of bones and teeth . The three examples of species that was found to synthesize vitamin K2 are Escherichia coli, Mycobacterium phlei, and Bacillus subtilis .
But vitamins are not the only beneficial substances produced by the bacteria living in our intestine. Gut microbiota synthesize bioactive metabolites and an example of them are the short chain fatty acids (SCFA). Short chain fatty acids are produced through saccharolytic fermentation of partially and non-digestible polysaccharides that become available to the gut microbiota . SCFAs are most abundant in the proximal colon. They can be used there by the enterocytes, which are predominant, tall columnar cells in the small intestinal mucosa responsible for the final digestion and absorption of nutrients, electrolytes and water or transported into the bloodstream across the gut epithelium . The major short chain fatty acids produced are formate, acetate, propionate, lactate and butyrate28.
Propionate is produced from deoxy-sugars, such as fucose and rhamnose mainly by the Akkermansia municiphilla, while Ruminococcus bromii synthesize the butyrate by fermentation of the starch . The first role of SCFA is being the energy source for cells building the colon tissues. There is evidence that SCFAs may reduce levels of cholesterol and glucose, which in excess can lead to cardiovascular disease. Also the right concentrations of butyrate, propionate, and acetate maintain the immunological balance at mucosal surfaces in the gut . It was found that SCFAs promote the expansion of regulatory T cells (Tregs) and butyrate has the ability to impact on differentiation of these cells31.
There is something else that, maybe not for a large scale, but can be synthesized by intestinal microbiota. Gut microbes are able to produce measurable quantities of the essential amino acids25. They have also their contribution in the nitrogen balance. Urea, which cannot be broken down by mammals, passes from the bloodstream to the gastrointestinal tract. It is transported by the urea transporters. Intestinal microbes that synthesize an enzyme called urease are able to cleave urea into ammonia and carbon dioxide. The bacteria then produce amino acids and peptides, utilising the ammonia (source of nitrogen). The microbial products can re-enter the host circulation, due to the presence of the amino acid and peptide transporters and act as a substrate for synthetic processes. This is the way that the intestinal microbiota participate in the process called urea nitrogen salvaging (UNS) , shown in Fig. 2 .
Genitals
Now, let’s take a closer look at the reproductive system, which is a home for more beneficial microorganisms. The most abundant genus of bacteria in the women reproductive tract is the Lactobacillus . It was found to have many important functions, essential to keep the system in homeostasis. First of all, Lactobacillus use glycogen, which is stored in the epithelia of the vaginal tract (this process is stimulated by the hormone oestrogen) in the fermentation, producing lactic acid. This production significantly helps to maintain the right, acidic pH in the vagina (lower than around 4.5). The acidic environment in the reproductive tract decreases its chance of being colonized by pathogens . Besides that, Lactobacillus can prevent the infections in various different ways. They are able to counteract the adhesion of pathogens to the tract surfaces34 and inhibit their growth by the release of bacteriostatic and bacteriocidal compounds3, which interfere with pathogenic cellular metabolism . By taking all the available nutrients, the Lactobacillus eliminates pathogens through the competitive exclusion3.
Viruses
However, what we have to remember is that beneficial microorganisms are not only bacteria. Our organism can be a home for commensal viruses, which also may protect us against pathogenic viruses responsible for infections. There is an estimation made, that about three-quarters in every billion of people have got pegivirus C infection with higher number possessing antibodies from previous infections. Pegivirus C (GBV-C) was found to alleviate the effects of HIV infection. There is also supporting evidence showing that patients infected with both HIV and pegivirus C seem to have longer life expectancy than patients possesing only the HIV infection. In addition, human resident viruses prefer cells that divide faster, which means that viruses could be used to infect and fight cancer cells .
As we can see there is a number of important groups of microbes playing fundamental roles in our organisms. Even though there is evidence to make this claim there is still more research to be done, because there are fields where scientists are not sure about the beneficial role of the presence of microorganisms. For example, there is not enough evidence to state that we benefit from the presence of certain types of fungi in our body and there is also little known about the microbes living in the male reperoductive tract. However these fields are under constant investigation1, so it’s very likely that in the future we will know even more about the human microbiome and it’s beneficial role and contribution to human health. The importance and benefits of the ecosystems living in our body need to be highlighted to make us appreciate their presence.
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