Gut Bacteria and Human Health
PKGhatak, MD
Every surface of the human body harbors microorganisms of various kinds, some are just parasites others live in symbiosis. When the symbiotic relationship breaks down for one reason or another, the health of the body is adversely affected. Recent studies on Gut bacteria show these actions are both local and systemic including immune mediated diseases. Dominant gut bacteria are Firmicutes, Bacteroides, Actinobacteria, Proteobacteria, Fusobacteria and Verrucomicrobia. However, Firmicutes and Bacteroides account for 90 % of the gut bacteria. About 10 to the power 10 number of bacteria are present per gram of feces in a normal state of health.
Firmicutes:
Firmicutes phylum is composed of more than 200 different genera such as Lactobacillus, Enterococcus, Clostridium and Ruminicoccus.
Firmicutes bacteria produce fermentation of undigested carbohydrates and cellulose and produce intestinal gases and Lactic acid, It releases antioxidants and micronutrients. The growth of colonies of firmicutes in the colon plays an important symbiotic relationship. Humans provide food for the bacteria and Firmicutes in return supply micronutrients, suppress the growth of disease causing bacteria namely enteric staph, anaerobic bacteria and Clostridium difficile.
Bacteroidetes:
Bacteroidetes are gram negative pleomorphic rods, non-spore forming, anaerobes and are both helpful bacteria of the gut but also may cause anaerobic infection under certain conditions. In a normal symbiotic existence, the Bacteroidetes break down undigested simple sugar, complex sugar, fat and protein in the gut and support other gut bacteria and also supply the human hosts with vitamins and micronutrients. A diet rich in oats, onion, ginger, flax seeds, and apples is a good food source for the Bacteroidetes.
The ratio of 20: 620 between Firmicutes and Bacteroidetes indicates a normal ratio and indicates good health of the individual. When the ratio tilts toward Firmicutes is generally associated with increased calorie absorption from the gut, insulin resistance and obesity indicating a chronic inflammatory environment leading to cardiovascular disease propensity.
Immunoglobulin A.
Peyer's patches of the small intestine and B lymphocytes in the lamina propria of the colon produce IgA antibodies. Gut bacteria are in a seesaw relationship with gut IgA. Bacterial antigen stimulates IgA antibody production and antibodies keep bacterial growth in check.
How symbiotic relationships develop.
The foreign antigen detection cells are Dendritic cells. In the gut, the dendritic cells are present in a loose connective tissue layer just beneath the gut epithelium and are in close proximity with the gut bacterial colonies. This constant contact has produced a state of "Inflammation Anergy" and the dendritic cells do not collect bacterial antigens and as a result, the macrophages do not produce pro- inflammatory cytokines.
IgA associated diseases:
Though IgA antibody production is highest among all Immunoglobulins, very little IgA antibody enters the blood; IgA is almost exclusively used up in the gut. In diseases due to IgA deposits in tissues, the IgA can be detected by Immunohistochemical staining of tissues.
COVID-19. The covid virus infects the gut mucosa, and the IgA antibodies try to eliminate the virus by its neutralizing action, however, in a small number of cases the elimination is only partial and COVID-19 virus is detected in feces for a long time.
IgA Nephropathy (IgA N). It used to be known as Berger's disease.
IgA Nephropathy is the most common type of Nephropathy in Asia and also in the world.
It is postulated that the respiratory tract bacteria produce Degalactosysation of IgA molecule. This degalactosyzed IgA (dIgA) becomes an antigen and antibodies are produced. Then antibodies and dIgA combine and this Antigen + Antibody complex is deposited in the extracellular matrix of Glomeruli of the kidney leading to IgA Nephropathy. The previously held theory was that aberrant glycosylation of IgA leads to polymerization of IgA and because of the complex's large size these complexes are deposited in the mesangium of glomeruli. Inflammation starts as a result and glomerulonephritis progresses to membranous glomerulonephritis with crescent formation.
Henoch Schönlein purpura.
Purpuric eruptions develop following a URI. The purpura is mostly seen in the legs, buttocks and sometimes in the hands, face and trunk. The purpura is more abundant along with the pressure points like socks line and waistband. Purpura is palpable and does not fade away on pressure. Children between 2 and 6 are mostly affected. Male children and white and Asian children are more venerable to HS purpura. The underlying pathology is a vasculitis of small vessels of the skin, mucous membrane and joints. Lesions in the mouth and arthritis may develop. GI symptoms are common and some also develop IgA nephropathy.
Skin lesions.
Dermatitis herpetiformis.
Clusters of raised red, intensely itchy lesions develop on elbows, knees, buttocks occasionally on arms and on the scalp. The lesions are intensely itchy. Often blisters develop from scratching and scar forms when opened up from scratch.
People of the age group 30 to 40 of European heritage develop recurrent lesions. Oral and GI lesions also occur. Aphthous ulcers in the mouth and pits and fissures on the enamel of teeth may appear, GI manifestations are bloating, cramps and diarrhea.
Cause.
IgA antibodies develop against the skin epidermal transglutaminase. It is the skin manifestation of Gluten enteropathy from gluten sensitivity.
Diagnosis.
Demonstration of IgA deposition in the upper layers of the dermis by immunofluorescence.
Dysmorphic Epidermolysis Bullosa.
IgA deposition at the junction of the basal layer of the epidermis and papillary cells of dermal held by collagen fibrils are damaged by the process. The epidermis is easily lifted off from the dermis with minor trauma. Blister formation and secondary infections are common. Epidermolysis Bullosa is an inherited disease. It is inherited by autosomal recessive and autosomal dominant modes and multiple gene mutations are present.
There are several clinical types based on clinical presentation and the associated involvement of other systems. GI, GU, Respiratory, ENT may variously be involved. It may be present at birth or at anytime later in life. It is a serious disease. There are serious complications. even when patients initially respond to treatment. Esophageal stricture and cancer are usual. Diagnosis is made by immunofluorescence staining of the biopsy tissues. The prognosis is variable but not good in general.
Summary.
IgA is the principal immunoglobulin in keeping the GI tract and other mucous membranes of hollow organs free of pathogens. Because of constant contact with bacteria, some of the bacterial degradation products/secretory enzymes become antigenic and antibodies are produced. Antibodies can react with normal tissues like nerve cells, GI cells, etc. This hypothesis has generated a new look into the pathogenesis of Multiple sclerosis, Parkinson's disease, etc. In the future, more and more laboratory confirmations will be available.
Lately, many attempts have been made worldwide to limit the use of antibiotics in supposed bacterial infections or recurrence, which are in fact infections from viruses. Also cut down the duration of antibiotics use from 15 to 5 days for an infection, like walking pneumonia and many other minor ailments. This practice will result in the return of a healthy symbiotic relationship between the gut bacteria and humans.
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