Scientific studies and knowledge on the gut microbiome and second brain (gut) are rapidly increasing. And their crucial influence on many aspects of health is already proven. The state of research, to follow.
The second brain is the enteric nervous system. A dense network of neurons (a hundred million, in the inner walls of the intestinal tract) that is closely connected to the autonomic nervous system and yet functions independently. The microbiome transmits information to the second brain (gut), which interacts with the first brain (central nervous system). In fact, the two brains communicate interactively along a bidirectional axis(gut-brain axis).
Microbiome, second brain and health. From pregnancy to follow
The microbial community present in the intestinal tract-as scientific research has amply demonstrated-plays a key role in modulating metabolic responses and the immune system.
The
microbiota
intestinal and bacterial metabolites have been associated with blood pressure regulation, chronic kidney disease, and cardiovascular disease. Changes in gut microbial composition have also been correlated with aging-related cognitive disorders, altered immune status and consequently to inflammatory bowel disease, allergy and asthma.
Numerous studies have also confirmed the important role that the gut microbiota plays in energy homeostasis. Namely, therefore, in the modulation of body weight (loss or gain) and the disorders associated with obesity and overweight.
The maternal microbiota may in turn exert an indirect effect on the fetus. Through factors, such as maternal immune responses or microbial metabolites, that can cross the placenta. Or even more indirectly, through factors that may mediate epigenetic programming in the fetus such as diet, stress, and exposure to neuroendocrine factors that also affect the maternal microbiota.
Childbirth and birth represent the first major exposure to the microbiota, and this is the primordial mechanism by which, in mammals, the microbiota is transferred between generations. We inherited the primordial microbiota from our mother and grandmother, along the matriarchal line extending to previous ancestors with vertical microbial transmission.
Microbiome and health, atavistic transmission and evolutionary interference
The human intestinal environment has changed dramatically during human and environmental evolution, however, where dietary changes and famines have been the main selective pressures. Industrialization and urbanization They have also radically altered lifestyles. Changes are complex, including human density, urban plan, houses, domestic architecture, ventilation, diet, clothing, exercise, personal care products, and medicines.
Selective pressures that shape microbiome characteristics in high-income countries include antibiotic exposure, pre- and postnatal period, toothpaste, soap, and perhaps even chlorinated water consumption. Urbanization is associated with increased risks of immune and metabolic diseases, including obesity, diabetes, gut pathologies, asthma, and behavioral disorders, and linked to this is reduced diversity of the gut microbiota.
In early childhood functions of the microbiota are likely to be central to understanding the etiology of urban chronic immune diseases. The risk of obesity, for example, has been epidemiologically associated with cesarean delivery and early exposure to antibiotics. After all, gestational use of antibiotics affects the colonization of the microbiota in children. As well as the ‘growth milk‘ formula Alters the microbiota of babies, compared with breastfed babies.
Research on the human prebiotic and probiotic functions of breast milk could lead to the design of synthetic formulas that respect the child’s developmental biology and contribute to infant gut health. Although it will take years to produce ‘synthetic,’ biologically appropriate human milk that can include hormones, cells, antibodies, and molecules such as glycans, complex carbohydrates, and HMOs(human milk oligosaccharides), which are affected by circadian levels.
Microbiome, the role of diet. Scientific Insight
Diet is the most important external factor in modulating the gut microbiota, and the ability of diet to alter microbial ecology was recognized as early as a century ago. Transient diet-induced alterations of the microbiome occur independently of body weight and adiposity and are detectable in humans as early as 24-48 hours after dietary manipulation.
Each of the major macronutrients and numerous micronutrients has been shown to modify the gut microbiome. Among the macronutrients, carbohydrates (CHO) are the best characterized. Especially simple ones such as sucrose, either alone or as part of a high-fat diet, cause rapid remodeling of the microbiota (in experimental animals) and subsequent metabolic dysfunction.
Complex carbohydrates, on the other hand, are formed by numerous monosaccharide molecules linked together. Among them are many monosaccharides that are indigestible to humans, the so-called fibers, which are a primary energy source of gut bacteria equipped with enzymes that can degrade them.
The fibers that can be metabolized by gut microbes are termed MAC, ‘carbohydrates accessible to the microbiota’ (other fibers, such as cellulose, are unusable). The best known MAC is inulin, a soluble fiber found naturally in many vegetables and fruits (especially in bulbs such as onions, Jerusalem artichoke and in tubers). Other MACs are found in legumes, in brassicaceae (cabbage, cauliflower, turnip, radish, arugula, mustard, rapeseed), and betonics (herbaceous perennial pasture plants).
Diets high in MAC alter the composition of the human microbiota within weeks, while a diet low in MAC decreases microbial diversity.
Prebiotics-the name originally used to describe a class of oligosaccharides that selectively increased the growth of Bifidobacterium and Lactobacillus-are a specific subgroup of MACs. These ‘canonical’ prebiotics are polysaccharides (fructo- and galacto-oligosaccharides) of different lengths, which change the composition of the gut microbiota.
Short-chain fatty acids (SCFAs)-the main end products of bacterial fermentation, representing a fantastic example of mutualism between humans and their bacterial symbionts-are in turn formed from MACs. SCFAs, via intestinal receptors, send ‘signals’ to the central nervous system. Aiming to modulate energy homeostasis (i.e., proper physiological metabolism of carbohydrates and lipids) and suppress inflammatory signals.
The two most important SCFAs, butyrate and propionate, could even epigenetically influence host gene expression. An individual’s energy balance state is thus ‘controlled’ by signals mediated by SCFAs, which are produced by gut bacteria.
The concept of prebiotic has been expanded in recent times due to technological advances that allow analysis of microbial responses to dietary components. Thus, the list of prebiotic candidates now goes on to include, for example, polysaccharide molecules not found in the diet, polyunsaturated fatty acids such as linoleic acid, phytocompounds, and phenolic compounds.
Polyphenols can modulate the gut microbiota in a process called the ‘prebiotic effect.’ The prebiotic effect of polyphenols has been studied in in-vitro assays, using human microbiota, and in preclinical and clinical studies with polyphenol-rich diets.
Green and black tea polyphenols, studied in-vitro on gut microbiota samples, showed the ability to significantly increase the abundance of Bifidobacterium and Lactobacillus, as well as improve SCFA production.
They are rich in polyphenols theextra virgin olive oil And some fruits, such as citrus fruits and pomegranate.
High levels of dietary fat, conversely, negatively alter the composition of the microbiota, especially the bacterial population in the small intestine, which has recently been shown to be highly sensitive to fat loading (and more generally to digestive processes and lipid absorption).
Primary bile acids, produced in the liver from cholesterol and secreted in the small intestine to facilitate solubilization and absorption of dietary lipids, are in fact modified by the microbiota by hydroxylation (i.e., inserting hydroxyl groups).
Gut-modified bile acids act as signaling molecules (in ways similar to SCFAs). The gut microbiota–by changing the composition of bile acids–regulates energy homeostasis, glucose metabolism, and innate immunity. This mode of microbiota/host interaction could have implications not only in lipid digestion and absorption, but also for the development and prevention of metabolic disease.
Le protein in turn modulate microbial composition, as amino acids provide essential carbon and nitrogen to gut microbes. The contribution of amino acids in total SCFA production is unclear, and other molecules formed from amino acid metabolism (e.g., indoles, phenols, ammonia, and amines) could also affect human health either positively or negatively.
Tryptophan – amino acid that abounds in milk and dairy products, sesame and sunflower, peanuts, eggs, oats-is used by intestinal microbial bacteria to form metabolites such as indole-propionic acid, which has been shown to play a role in maintaining intestinal homeostasis and protecting against colitis (experimentally induced in animal models). And indole-3-acetate, which has recently been shown to reduce inflammation in hepatocytes and macrophages.
Carnitine, an amino acid that abounds in meats, conversely leads to the formation of a ‘negative’ metabolite, trimethylamine oxide (TMAO). High TMAO levels are predictive of cardiovascular events, as well as being implicated in the development of hepatic steatosis.
Conclusions and perspectives
The Mediterranean diet is undoubtedly ideal at fostering a healthy and stable microbiota. A diet rich in fiber and carbohydrates, with plenty and variety of vegetables and fruits and a moderate intake of animal protein. In line with, among other things, the model of ‘
Healthy diets from sustainable food systems
‘ recently proposed in
Lancet
by a panel of experts with multi-disciplinary expertise.
Characterization of the ‘healthy microbiome’ is still extremely complex because of functional redundancies and taxonomic profiles (the diversity of living organisms), which can lead to microbial ecosystems with similar behaviors. It is therefore necessary to pursue research, which must also consider lifestyles and socio-environmental contexts.
After all, the ‘discovery’ of the gut microbiota as a key regulator of human physiology has already generated enormous interest in the scientific community, as can be seen from the exponential increase in publications on the subject in recent years. While awakening industrial interest in the prebiotic and probiotic market, with further stimulation of research.
L’
holobiont
human (‘thehost plus of all its microbial symbionts, including transient and stable members‘) is gradually being understood and its relationship to the host and its health and/or disease status is increasingly characterized. Efforts to standardize sample preparation and analytical protocols, and increasing international projects, will increasingly allow for the elucidation of still unclear points.
Some projects co-funded by the European Union-such as MetaHIT, which searches for an association between genes expressed by the microbiota and the health status of the host, as in the case of IBD (Inflammatory Bowel Disease), or METAMAPPER, which will investigate the role of the microbiota in the inflammatory processes and obesity etiology of cardiovascular and neurodegenerative diseases-will offer additional stimuli.
Paola Palestini and Dario Dongo
Bibliography
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Associate Professor of Biochemistry at the Department of Medicine and Surgery, since 2000 at the University of Milan-Bicocca, since 2014 he has coordinated the master in Applied Nutrition and Dietetics (ADA) and is the holder of Biochemistry in numerous degree courses and specialization schools. She is a member of the scientific council of the POLARIS center (Dust in the Environment and Health Risk) of the University of Milan-Bicocca, for the study of environmental nano- and micro-particles and their impact on human health. She is the author of 75 papers - published in peer-rewiev international journals - on the impact of environmental factors (food and air pollution) on health. She co-author of the book 'Mamma mia diet' (ed. Hatherleigh, 2018), aimed at promoting the Mediterranean diet in the world.
Dario Dongo, lawyer and journalist, PhD in international food law, founder of WIISE (FARE - GIFT - Food Times) and Égalité.
