Department of Clinical Physiology, Medical Center of Postgraduate Education, Warszawa
Head of Department: prof. Andrzej Beręsewicz, MD, PhD
Since 2008 there has been an international research project called Human Microbiome Project analyzing the biological roles of commensalistic bacteria settled in different areas of human body. This and other research suggest involvement of intestinal bacterial flora (IBF) in the mechanisms of different diseases, including such civilization diseases like obesity (1-8) and arteriosclerosis (9, 10). In this context it was proved that the bacterial inhabitants of the human gastrointestinal tract break down various alimentary composition and that the products of this process may have beneficial or unbeneficial biological effects. There are three kinds of substances important to obesity and arteriosclerosis development:
1. Short chain fatty acids, which are produced in the disintegration of complex polysaccharides and take part in the development of obesity.
2. Trimethylamine (TMA), which is a product of lecithin and L-carnitine bacterial metabolism and which, after oxygenation by the hepatic enzyme into TMAO, has a pro-arteriosclerotic effect.
3. Protocatechuic acid (PCA), which is a product of plants flavonoids bacterial metabolism and which has an anti-arteriosclerotic effect.
The current hypothesis is that there are individual differences in the IBF composition and that some quantitative and qualitative proportion of IBF have beneficial and others unbeneficial effects. It is widely known that lean and obese people have different kinds of IBF. In this article I present IBF content and biology as well as its role in development of obesity and arteriosclerosis.
Alimentary tract of a newborn mammal is sterile. With birth the process of alimentary tract colonization by bacteria begins. In humans the more or less final composition of IBF is settled when the child is introduced on the same diet as adult family members (11). The amount of intestinal bacteria in an adult human is estimated to 1013-1014 microorganisms (~1 kg of bacteria), which means that we have ~10 times more bacteria that our own cells in the intestines only (12). Human IBF (but also mice’s) contain mainly anaerobic bacteria belonging to five phyla: Firmicutes (64%), Bacteroidetes (23%), Proteobacteria, Actinobacteria i Verrucomicrobia, consisting of totally 1000-1500 bacterial species (13). In human intestine there are also viruses, protozoons, archeons and fungi (14).
There are individual differences in IBF composition. These may be quantitative differences (in the percentage of different phyla/species in the whole amount of bacteria) and qualitative (in the amount of IBF species). The differences in IBF species composition are determined by: geographical area of origin, environmental hygiene conditions and genetics (in uniovular twins the differences in IBF composition are minimal) (1). The species composition of the human intestinal microbiota is also determined by: (a) prematurity – in premature infants there were mainly anaerobes (Klebsiella, Enterobacter) and Bifidobacterium, Enterobacteriaceae and Lactobacillus bacteria occur much later than in children born in term (15); (b) the kind of delivery – natural vs by cesarean section (16); (c) the kind of feeding – in children fed with breast milk there are mainly Bifidobacterium bacteria and in children fed with modified milk IBF is more differentiated (16, 17); (d) feeding habits in adult period, e.g. “carnivores” vs vegetarians/vegans (9, 18, 19); (e) undergoing antibiotic therapy (20); (f) past bariatric operation (21); (g) pregnancy (22-24) and (h) ageing (25).
IBF has numerous beneficial biological effects, including intestinal peristalsis stimulation, influences the development of intestinal villi and rebuilding of epithelium and has also positive effect on maturation and activity of alimentary tract immunological system (26). Lately there have been numerous reports on the role of IBF in development of different pathologies.
There are the following arguments for the engagement of IBF in obesity development:
1. Germ-free mice (deprived of intestinal microflora) are thinner than mice with IBF even if they are fed in the same way. It partly is a result of the fact that germ-free individuals do not have intestinal villi developed, which may impair intestinal absorption. Another reason is that IBF takes part in digestion of complex polysaccharides (like fiber), which are not digested by the host’s alimentary tract. The products of bacterial fermentation of these substances are short-chain fatty acids (acetic acid, lactic acid, propionic acid, butyric acid), which when absorbed are the additional source of energy. In humans, IBF “delivers” about 80 to 200 kcal per day, which is 4-10% of the daily energy demand (2). The same fatty acids are, additionally, agonists of specific G protein-coupled receptors – GPR41 and GPR43. These receptors are also known as the free fatty acids receptors – FFAR3 and FFAR2. Their activation causes increased intestinal absorption and adjusting fat tissue metabolism into increased fat accumulation (27).
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