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
Corresponding author details:
Giuseppe Merra, Adjunct Professor,Staff Physician
Emergency Department
Agostino Gemelli” General Hospital Catholic University of Sacred Heart
Rome,Italy
Copyright: © 2019 Giuseppe Merra et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 international License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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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