Intestinal Microbiota: A New Actor in the Fight Against Obesity?

Merra G1*, Capacci A2, Ferrigno F1, Di Renzo L3, Franceschi F1, De Lorenzo A3

1 Emergency, Anesthetic And Resuscitation Sciences Department, A. Gemelli” General Hospital Foundation IRCCS, Catholic University of Sacred Heart, Largo Agostino Gemelli, Rome, Italy
2 Gastroenterological, Endocrine-Metabolic, Renal And Urological Sciences Department,  “A. Gemelli” General Hospital Foundation IRCCS, Catholic University of Sacred Heart, Rome, Italy
3 Section of Clinical Nutrition and Nutrigenomic, Department of Biomedicine and Prevention,  University of Rome Tor Vergata, Rome, Italy

CitationCitation COPIED

Merra G, Capacci A, Ferrigno F, Di Renzo L, Franceschi F, et al. Intestinal microbiota: a new actor in the fight against obesity? Biomed Res Rev. 2019 Mar;2(2):109.


Intestinal microbiota; Fight; Obesity

The human intestine contains over a thousand species of diners microrganisms, collectively known as “intestinal microbiota”, essential to the integrity of the mucosal barrier function. Alterations such as quantitative of microbiota (composed mainly of bacteria, viruses and fungi), which are able to alter this delicate balance, are involved in neurological and systemic diseases (among others, Ulcerative Colitis and Crohn’sdisease, irritable bowel syndrome, stomach and colon cancers, allergies and intolerances, diabetes, atherosclerosis, etc.). Laboratory and human studies also showed an interesting relationship between gut microbiota and obesity [1,2]. Obesity is a medical condition which affects a growing number of people, especially in Western countries. In the United States more than 50% of the population is overweight and about 1/3 is frankly obese. It is also a predisposing condition for a number of diseases that can seriously compromise the health of the individual. No doubt a high-calorie diet and lack of physical activity are the leading causes of obesity, but certainly fascinating is the study of the complex mechanisms involved in the regulation of energy balance and their alterations. In this regard, recent studies suggest that the gut microbiota can play an important role in the pathogenesis of obesity and metabolic syndrome as able to influence nutrient absorption and distribution of energy. Mice bred in sterile conditions (the so-called “germ free”, scilicet without microbiota) need a significantly higher amount of calories compared to the counter part grown under conventional conditions to maintain the same body weight and, in equal diet, have a considerably lower amount of fat mass. Very interesting is that the subsequent colonization of germ-free mice with a normal colonic microbiota determines a rapid and significant increase in body weight and body fat of these animals. Underlying these evidences there are a variety of mechanisms. Bacteria of the microbiota, in fact, appear likely to reduce intestinal expression of a factor, the fastinginduced adipose factor (Fiaf), which is itself an inhibitor of lipoproteinlipase. It follows an abnormal activation of this enzyme, which favor the release of fatty acids from circulating lipoproteins VLDL and chylomicrons with subsequent accumulation of triglycerides in the adipose tissue. Intestinal bacteria are also able to reduce expression, whether in the liver that muscular, of an enzyme, AMPK (adenosine monophosphate-activated protein kinase), which is critical in stimulating β-oxidation of fatty acids. Another recently described mechanism involves rather short-chain fattyacids produced by bacterial fermentation of carbohydrates, which are able to regulate the expression of intestinal hormones, such as Peptide YY, which regulate the production and digestive enzyme release. Finally, monosaccharides produced by fermenting bacteria action of the microbiota, once absorbed and transported to the liver by the portal circle, are able to bind and activate a cytoplasmic factor ( the carbohydrate responsive element binding –ChREBP), which, migrating from the cytoplasm to the nucleus, activates enzymes involved in lipogenesis. Finally, another highlight on the possible role of intestinal flora in obesity comes from the evaluation of the role of lipopolysaccharide (LPS) of the wall of gram negative bacteria in chronic systemic inflammation and therefore insulin resistance and obesity. High-fat diets in particular alter composition of the microbiota (increase Gram negative bacteria/Gram positive) leading to increased levels of circulating LPS; this, in turn, is able to induce the production of pro-inflammatory cytokines (TNF-α, IL1, IL-6, plasminogen activator inhibitor) [3,4] which in turn regulate the glucose tolerance, encouraging the development of insulin resistance [5]. It follows then a possible role of LPS in chronic inflammation associated with diets [6,7] high in fat, with a predisposition to the development of insulin resistance and thus of diabetes. Is easy to understand, therefore, that both experimental animals and humans there are significant differences in the composition of the microbiota [8-15] between qualitative and quantitative obese and lean. In particular, recent studies have clearly demonstrated a significant reduction of bacteria belonging to the family of Bacteroidetes and a proportional increase of bacteria belonging to the family of Firmicutes and Archea. This results in an increase in the intestinal lumen, of non-digestible polysaccharides capable of breaking down hydrolases, including the β-fructosidases and increased transport proteins needed in absorption of products of fermentation, including the Phospho transferases. Always in obese, the preponderance of methane-producing bacteria, which use hydrogen to produce methane, maintains a constant low hydrogen partial pressure, thus optimizing the processes of bacterial fermentation [16-18]. Ultimately, these quantitative and qualitative changes in metabolic way of bacterial flora guarantee guests to extract maximum energy value from the diet, taking calories also in even potentially low foods, like fibers. The surprising is that these alterations of gut microbiota are absolutely reversible: a low-calorie diet, in fact, is able to balance Bacteroidetes/Firmicutes, reformulate the metabolic structure of the intestinal flora and induce a weight loss that goes along with the balance of the intestinal ecosystem. At present, antibiotics, probiotics, prebiotics and synbiotics are tools used to modulate the bacterial flora in terms of quality and quantity [19-21]. It is clear that an ever deeper knowledge in this field and new data on bacteria able to influence the metabolism, such as Akkermansiamuciniphila, or inflammation, such as Fecalibacteriumprausnitzii may in the future to suggest therapeuticactions on complex microbial intestinal balance which is the basis of obesity and its complications.


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