Microbiota: role and impact on health and disease

Jun 9, 2021

We have been always considered microbes as enemies to kill. Actually, with recent advances in DNA-based technologies started a couple of decades ago, we completely revolutionized this concept. Our body is entirely covered and populated by a hundred thousand billion microbes, living outside and inside our body. Except for those exerting pathogenic activities, they are good microbes, essential for several activities. Today, rather than microbes we talk about microbiome, referring to the total amount of microbes, namely bacteria, viruses, and fungi living within our body, more specifically, according to the anatomical localization, five big classes of the microbiome can be highlighted: oral, cutaneous, placental, vaginal, and intestinal (or gut) microbiome. The latter has raised quite an interest, since the maintenance of the eubiosis condition, a correct balance among the different families of gut bacteria, is important for the several physiological processes they are involved in. Among them, gut bacteria exert key roles in pathogen protection, nutrition, host metabolism, and immune modulation. Contrary, its alteration, or dysbiosis, is linked to the onset of several pathological conditions.

Factors inducing dysbiosis

Many endogenous and exogenous factors may lead to gut microbiome alteration. Its effects range from acute to chronic, with the consequences going from being harmless to harmful. Antibiotic therapy is one of the most important agents leading to dysbiosis, given by the mechanism by which antibiotic drugs kill unselectively both bad, or pathogenic, and good non-pathogenic bacteria as well. Despite this one, often a single factor is not enough to trigger gut dysbiosis, but two or more factors are necessary. The main ones leading to gut dysbiosis are, among others, diet, obesity, some drugs, immune system, intestinal diseases.  Despite the term dysbiosis we refer to a general gut microbiota alteration, actually, there are different types of gut dysbiosis but, at the same time, a “common ground” hypothesis has been suggested as the common factor at the basis of any kind of gut dysbiosis. This hypothesis bases on an intestinal epithelial barrier impairment triggered by exogenous (unhealthy diets or contaminants) and endogenous factors (inflammatory or metabolic stress) leading to a low-grade immune activation with consequent pressure on the intestinal microbiota. This results in a subclinical phase in which impairments of epithelial tight junctions occur as well as mucosal abnormalities, thus favoring a passive bacterial internalization. This chronic process will lead to the clinical form so to overt gut dysbiosis.

Dysbiosis and diseases

It starts becoming quite evident that an alteration of the gut microbiota is related to the onset of many diseases, that can be grouped into two main classes as Gastrointestinal (GI)-tract-related disorders, and Central Nervous System (CNS)-related disorders.  Regarding GI disorders, many studies have shown that intestinal microbial dysbiosis plays a key role in the pathogenesis of Inflammatory Bowel Disease (IBD), being Crohn’s Disease (CD) and Ulcerative Colitis (UC) the most representative ones. The intestinal microbiota of these patients shows a significant impairment of Firmicutes and Bacteroidetes species. The chronic inflammatory intestinal condition does the groundwork for colorectal cancer development, which seems to be linked to gut dysbiosis. The gut-brain axis is the existing link for gut dysbiosis and CNS disorders so that many studies showed how pre-and probiotics supplementation has a positive impact. A possible explanation comes from the role that intestinal microbiota has on cognitive function and behavior by influencing the hypothalamus-pituitary-adrenal (HPA) axis. Similarly, commensal bacterial may directly influence immune and neural receptors at the enteric and central nervous systems through GABA neurotransmitters, a mechanism postulated to be at the basis of anxiety and depression. The link between gut dysbiosis and CNS disorders is so strong that gut microbiota is now commonly considered as the “second brain”.

Dysbiosis and PCOS

Although the link between gut dysbiosis seems and GI and CNS disorders appears to be evident, the latest evidence on Polycystic Ovary Syndrome (PCOS) is quite interesting. Recent studies have shown that gut microbial dysbiosis in women with PCOS is associated with the disease phenotypes. PCOS patients have been reported having increased dysbiosis when compared to healthy women, both lean and obese, and this dysbiosis worsens with the BMI, being accentuated in obese PCOS women rather than lean PCOS women. This impairment involves bacteria belonging to the genera Akkermansia, Bacteroides, Clostridium IV, Lactobacillus, Oscillibacter, all of them higher in healthy women and lower in lean PCOS women and, even more, in obese PCOS. These impairments correlate with PCOS-related signs and symptoms, such as obesity, inflammation, hyperinsulinemia, hyperandrogenism, abnormal ghrelin level, and psychological state, suggesting that a link between PCOS and dysbiosis exists, and this impairment should start to be considered as a characteristic of the syndrome.

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