THE GUT MICROBIOTA

Microbiota refers to the set of all microbes (viruses, bacteria, archaeobacteria, protozoa, fungi) that are commensal, symbiotic or pathogenic living in our bodies. The composition of the gut microbiota is influenced by many factors such as age, sex, dietary habits, and lifestyle. Recently, numerous scientific studies have demonstrated an involvement of the microbiota in immune-mediated diseases such as rheumatoid arthritis, psoriasis, lupus erythematosus, multiple sclerosis, diabetes mellitus type I, and chronic inflammatory bowel disease. Alterations in the proportions of the various strains of microorganisms that make up the gut microbiota(dysbiosis) appear to be implicated in changes in the body’s immune responses, both physiological and pathological. In addition, the microbiota appears to influence the activity of T lymphocytes, not only in the gut but also in the skin ( gut-skinaxis) and remote organs.

THE FUNCTIONS OF THE MICROBIOTA

The gut microbiota ferments undigested carbohydrates (prebiotics) such as fructooligosaccharides, oligo-fructose, inulin, galactose, and xylose. The microbiota influences metabolism, the physiology of the digestive system, the function and development of the immune system, and possesses a symbiotic function related to vitamin biosynthesis, protection of colonization by pathogenic microorganisms, regulation of neuronal signals, and modulation of gastrointestinal hormone release.

COMPOSITION OF THE MICROBIOTA

More than 90 percent of intestinal bacterial species belong to the phyla Bacteroidetes, Firmicutes eto a lesser extent Actinobacteria. the alteration of the Firmicutes/Bacteroidetes ratio as well as that between grampositiv/gram negative (LPS-producing, pro-inflammatory) is implicated in several pathological conditions.

The phyla that make up the gut microbiota are as follows:

• Actinobacteria (Gram-positive):Bifidobacterium, Collinsella, Eggerthella, and Propionibacterium.
• Bacteroidetes (Gram-negatives): more than 20 genera including Bacteroides, Prevotella and Corynebacterium.
• Cyanobacteria (Gram-negatives).
• Firmicutes (Gram-positive): at least 250 genera including Mycoplasma, Bacillus, Clostridium, Dorea, Faecalibacterium, Ruminococcus, Eubacterium, Staphylococcus, Streptococcus, Lactobacillus, Lactococcus, Enterococcus, Sporobacter, and Roseburia.
• Fusobacteria (Gram-negative):Sneathia.
• Lentisphaerae (Gram-negatives).
• Proteobacteria (Gram-negatives): Escherichia, Klebsiella, Shigella, Salmonella, Citrobacter, Helicobacter, and Serratia.
• Spirochaeates (Gram-negatives).
• Verrucomicrobia (Gram-negatives).

GUT MICROBIOTA IN ALOPECIA AREATA

Alopecia areata is considered to date to be a disease with predominantly autoimmune pathogenesis, characterized by an infiltrate consisting mainly of self-reactive CD8+ T lymphocytes at the level of the hair follicle. Also for the pathogenesis of alopecia areata, as for many other immunologically based disorders, the role of both skin and intestinal microbiota has recently been studied.

In particular, studies in animal models suggest a crucial role of the gut microbiota in the development of alopecia areata, which does not occur in animals treated with cocktails of broad-spectrum antibiotics.

Some clinical studies have documented the presence of dysbiosis in patients with alopecia areata compared to healthy controls. In recently published work, it was demonstrated with increased relative abundance of the phylum Firmicutes and decreased relative abundance of the phylum Bacteroidites, particularly Ruminococcussp., Alistipesshahii and some lactobacilli. The work of Liu et al. showed an increase in the relative abundance of Actinobcteria and reduction in Bacteroidetes and Fusobacteria compared with controls. In addition, patients with areata were found to have an abundance of the genera Blautia (also increased in psoriasis and rheumatoid arthritis), Pseudomonas Collinsella, Megasphaeraand Dorea (also abundant in IBD, rheumatic diseases, thyroiditis, Parkinson’s, psoriasis).Finally, the study by Moreno-Arrones et al. found an increase in some families of Firmicutes (Holdemaniafiliformis, Erysipelotrichacea and Lachnospiraceae, Clostridiales vadin BB60) and Bacteriodites (Parabacteroides johnsonii, Bacteroides eggerthii, and Parabacteroidesdistasonis) in patients with universal alopecia areata.

The observed alterations in the composition of the microbial flora could be responsible for An alteration in the production of short-chain fatty acids (acetate, succinate, butyrate), major metabolites produced by the digestion of soluble fibers by the microbiota. These are absorbed by enterocytes constituting an important source of energy and especially by regulating T lymphocyte gene expression, reg T lymphocyte proliferation, and reducing inflammation. In addition, the reduction of short-chain fatty acids appears to be involved in the impairment of the integrity of the intestinal barrier (leakygut), which is critical for preventing the passage of microbial agents, toxins, and antigens and for promoting nutrient absorption. Loss of intestinal barrier integrity has been associated with inflammatory bowel disease, type I diabetes mellitus, celiac disease, and recently evaluated as a trigger for alopecia areata.

Finally, gut dysbiosis could contribute to an increase in oxygen free radicals and a reduction in antioxidant defenses resulting in increased oxidative stress, another important mediator in the pathogenesis of alopecia areata.

These observations, together with reports are in the literature regarding hair regrowth in patients with alopecia areata following fecal transplantation, suggest an important role of the gut microbiota in its pathogenesis.

PROBIOTICS.

According to the WHO definition, probiotics are live microbial strains that provide health benefits when taken in a certain amount. These have been the subject of much research for their potential use in modulating the gut microbiota.

During the 20th century, the importance of consuming foods rich in probiotics, such as yogurt, emerged to maintain good health through proper functioning of the digestive tract and prevention of degenerative diseases.

Most probiotic products developed to date contain Bifidobacteria, Lactobacilli, Lactococci, and Streptococci. Other promising strains include bacteria from the genus Bacillus, Escherichia, Propionibacterium and among other genera Saccharomyces.

Probiotics are considered safe for humans with minimal adverse events.

Many species of Lactobacilli, such as L. casei, L. rhamnosus, and L. acidophilus, have been extensively studied for the prevention of various diseases, both in animal models and in humans, since they have demonstrated the ability to induce changes in the composition of the intestinal microbiota.

LACTOBACILLI

Studies in animal models have shown a change in the composition of the intestinal microbiota in mice exposed to a high-fat diet, a reduction in intestinal permeability, and an improvement in insulin sensitivity following treatment with probiotic species of Lactobacilli (L. rhamnosus, L. acidophilus, L. casei). Commensal Lactobacilli appear to restore intestinal homeostasis and play a protective role against inflammatory diseases. A recent study observed a reduction in pro-inflammatory cytokines (IL-6, TNFa, IL-1b) in the intestine and a balance in the ratio of Th17/Treg lymphocytes in animals with colitis treated with L. acidophilus.

BIFIDOBACTERIA

Bifidobacteria can inhibit the growth of pathogenic bacteria, improve intestinal barrier function, and reduce levels of proinflammatory cytokines. Administration of Bifidobacteria increases the production of short-chain fatty acids in the intestine. Finally, Bifidobacteria appear to exert a positive effect at the central nervous system level by modulating the activity of the gut-SNC axis. Improvement in stress- and depression-related symptoms has been reported following treatment with combinations of Lactobacilli and Bifidobacteria.

SACCAROMYCES

In recent decades S. cerevisiae e S. boulardii have been shown to change the composition of the microbiota by increasing the relative abundance of the Bacteroidetes and reducing that of the Firmicutes and the Proteobacteria. In addition, their administration appears to prevent the occurrence of intestinal inflammationthrough the regulation of immune system activity and increased production of short-chain fatty acids.