The Human Microbiome in Health and Disease

The Human Microbiome in Health and Disease

INTRODUCTION, the biome, number of organisms

Various parts of the human body provide favourable (while selective) environments for microorganisms. The skin, mouth as well as the respiratory, gastrointestinal and urogenital tracts all have unique environments which cater to particular bacteria while some are vulnerable to particular infections. The natural microflora of the human body number approximately 1014 – 1015 and are important in health while a small number of microorganisms called pathogens can infect the body and cause disease.

Not all organisms are present in all individuals. Distribution and prevalence differ with age and sex. Every individual has, to some extent, a unique microbiome. While sterile in the womb, we accrue microbes from adults and the environment during the first years of life, giving each of us a random, unique microbial population.

Part to play in health and disease

MAIN ROLE IN HEALTH-

Normal flora consist of normal commensals (exactly which are present is affected by the individuals HLA type) present in the aforementioned ‘carrier sites’ and occasional commensals, which are environmentally common but less frequently seen in humans than normal commensals. Occasional commensals can be present in the body without causing harm.

This normal flora confers ‘colonisation resistance’, protection from invasion by other microbes. Disruptions to normal flora such as treatment with broad spectrum antibiotics can allow opportunistic pathogens like Clostridium difficile to become established. Any repression of the immune system (such as that caused by radiation or fatigue) can provide an opportunity for infection by opportunistic pathogens.

 

Table of normal microflora

Some of the typical microflora will be listed in the following table. We will then discuss each region and assess how it benefits from its own microbial population and the unique pathogens it can be subject to.

Skin:  Staphylococcus, Streptococcus, Actinobacteria, Firmicutes,

Mouth: Streptococcus, Candida (fungi), Actinomyces,  Fusobacterium,

Respiratory tract: Staphylococcus, Streptococcus, – none in lower resp tract

Gastrointestinal tract: Staphylococcus, Streptococcus, Fusobacterium, Clostridium,  Bacteriodes,

Urogenital tract: Staphylococcus, Streptococcus, Lactobacillus,

 

SKIN, environment, unique beneficial bacteria, unique pathogens

The epidermis is in many ways the first line of defence and primary point of interaction with outside microbes. It presents three distinct environments across the body: moist areas (nostrils, armpits), dry areas (palms, forearms) and areas with sebaceous glands (upper chest, back). The normal microflora here are predominately gram positive, ~50% Actinobacteria and ~25% Firmicutes. The remaining gram negative bacteria are mostly Proteobacteria.

Environmental temperature may alter the moisture of the skin and cause fluctuations in bacterial populations while personal hygiene can alter this as well (poor hygiene resulting in greater density of microbes living on the skin). Additionally, young children typically have a more unusual, erratic microflora with a higher potential for pathogens than adults.

The Staphylococci, especially Staph aureus are common in most people and under certain conditions can cause disease. Staph aureus skin infections can result in a range of diseases including: boils, wound infection, abscesses and more seriously, scalded skin syndrome in young children. People with certain skin diseases such as atopic dermatitis are at particular risk.

DENTAL/ORAL, environment, beneficial and pathogenic bacteria

The oral environment contains three niches for flora: tongue, saliva, and dental plaque (both approximal and subgingival). Spatial arrangement of the teeth may present crevices for food to become trapped (presenting a growth medium). Saliva presents a poor growth medium as it has low levels of nutrients and contains lysozyme giving it antibacterial properties. Thus the focus of dental microorganisms is the teeth and to a lesser extent, the tongue.

Normal flora is varied, Actionomyces is usually most prevalent ~4%. Most are facultative anaerobes, some olbligately anaerobic and a few are aerobic. Beyond the general benefit of colonisation resistance, mouth flora provide protection from foreign bacteria by producing inhibitory substances such as fatty acids as well of vitamins of nutritional use to the host.

Around 40% of adults harbour commensal Candida species. Thrush or oral candidiasis occurs in ~5% of newborns due to their nascent host defences, while antibiotics or immune deficiency (such as HIV infection) are predisposing factors for adults. This is commonly caused by the dimorphic fungus Candida albicans and manifests as a creamy white coating on the tongue or soft palate.

Plaque is formed when saliva forms a thin glycoprotein film over the tooth which is then used as an attachment site by microcolonies. Over time bacteria such as Streptococci colonise this film creating plaque. Given enough time filamentous anaerobes like Fusobacterium can grow, embedding on layer of Streptococci plaque. When plaque consists of bacterial film of multiple genera it is considered a mixed culture biofilm.

GIT

By far the most active and populated site of microflora in the body (containing approximately 10 times as many bacterial cells as there are human cells in all of the body), GIT microflora have a profound effect on health and disease. The majority is bacteria, while fungi and protozoa can also be present.

The bacteria found across the GIT are heterogeneous, the acidic environment of the stomach offering a different niche to the more favourable conditions of the large intestine. The vast majority are Gram positive and belong to genera: Bacteriodes, Clostridium or Fusobacterium.

The typical human harbours a complex microbial ecosystem of 400 or more bacterial species. As such it is difficult to ascertain the specific benefit of any one bacteria and preferable to consider the gut biota as a functional whole, whose component parts interact to benefit the host subsistence.

These bacteria contribute greatly to metabolism, producing essential vitamins (B12, K) and enzymes for the breakdown of polysaccharides which would otherwise be wasted. Experiments by Ivanov et al found that diminishing the commensal microbiota of mice with antibiotics markedly reduced the number of TH17 CD4 immune cells present in their small intestine.  This suggests that commensal bacteria play a role in regulating the host immune system – a lack of TH17 cells makes the host more susceptible to Inflammatory Bowel Disease.  Thus the gut biota goes beyond colonistaion resistance, actively equipping the immune system and preventing inflammatory diseases like Crohns disease.

Disease mainly occurs due to imbalance in microbial population, brought about by antibiotic treatment which kills antibiotic susceptible bacteria and allowing pathogens to take their place. This is not always the case, the Gram negative microaerophle Helicobacter pylori causes gastric ulcers and is linked to stomach cancer. It is present in around 50% of people although causes symptoms in only one fifth of afflicted individuals.

Translocation refers to bacteria from the lumen entering extraintestinal parts of the body by crossing the mucosal lining. Typically small amounts of bacteria do translocate, but are destroyed by the immune system before causing damage. In times of immunocompromisation (such as after surgery) these translocations can cause serious disease such as sepsis, and Escheria coli is commonly the causal bacteria. Wounds which puncture the GIT (a perforated bowel) have a similar effect, allowing bacteria to spread to various parts of the body causing serious harm.

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