Scientific studies and knowledge on the intestinal microbiome and second brain (intestine) are rapidly increasing. And their crucial influence on many aspects of health is already proven. The state of research to follow.
The second brainit is the enteric nervous system. A dense network of neurons (one hundred million, in the inner walls of the intestinal tract) which is closely linked 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 communitypresent in the intestinal tract - as scientific research has amply demonstrated - plays a fundamental role in modulating metabolic responses and the immune system.
Il microbiota in the case ofand bacterial metabolites have been associated with blood pressure regulation, chronic kidney disease and cardiovascular disease. Changes in the gut microbial composition have also been related to cognitive pathologies related to aging, eg changes in the immune status
and consequently to inflammatory bowel diseases, allergy and asthma.
In fact, in numerous scientific studiesthey also confirmed the important role that the intestinal microbiota plays in energy homeostasis. Namely, therefore, in the modulation of body weight (loss or increase) and the disorders associated with obesity and overweight.
The maternal microbiotait can in turn have an indirect effect on the fetus. By factors, such as maternal immune responses or microbial metabolites, which can cross the placenta. Or, more indirectly, through factors that can mediate epigenetic programming in the fetus such as diet, stress, 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 through 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 environmenthowever, it has changed dramatically during human and environmental evolution, with dietary changes and famine being the main selection pressures. L' industrialization and urbanization they have also radically altered the lifestyle. The changes are complex, including human density, urban plan, homes, home architecture, ventilation, diet, clothing, exercise, personal care products, and medicines.
The selective pressuresthat shape the characteristics of the microbiome in high-income countries include exposure to antibiotics, the pre- and postnatal period, toothpaste, soap and perhaps even the consumption of chlorinated water. Urbanization is associated with increased risks of immune and metabolic diseases, including obesity, diabetes, intestinal pathologies, asthma, behavioral disorders and a reduced diversity of the intestinal microbiota is connected to this.
In early childhoodthe functions of the microbiota are probably fundamental for 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. The gestational use of antibiotics also affects the colonization of the microbiota in children. As well as the 'growth milk'in formulaalters the microbiota of babies, compared to those breastfed.
Research on prebiotic functionsand human probiotics from breast milk could lead to the design of synthetic formulas that respect the baby's evolutionary biology and contribute to infant gut health. Although it will take years to produce biologically appropriate 'synthetic' human milk, which may 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 study
The diet it is the most important external factor in modulating the microbiotaintestinal and the ability of the diet to alter microbial ecology was recognized as early as a century ago. Transient diet-induced changes in the microbiome occur regardless of body weight and adiposity and are detectable in humans as early as 24-48 hours after dietary manipulation.
Each of the major macronutrientsand numerous micronutrients have been shown to modify the gut microbiome. Among the macronutrients, carbohydrates (CHO) are the best characterized. In particular, 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 consequent metabolic dysfunctions.
Complex carbohydrateson the other hand, they are made up of numerous molecules of monosaccharides bound together. Among them there are many indigestible monosaccharides for humans, the so-called fibers, which represent a primary energy source of intestinal bacteriaequipped with enzymes capable of degrading them.
The fiberswhich can be metabolized by intestinal microbes are defined MAC, 'carbohydrates accessible to microbiota' (other fibers, such as cellulose, are instead unusable). The best known MAC is inulin, a soluble fiber found in nature in many vegetables and fruits (especially in bulbs such as onions, jerusalem artichokes and tubers). Other MACs found in legumes, in brassicas (cabbage, cauliflower, turnip, radish, rocket, mustard, rapeseed) and in betonic (herbaceous perennial grazing plants).
Diets high in MAC alter the composition of the human microbiota in a few weeks, while a diet low in MAC decreases microbial diversity.
I prebiotics- name with which originally a class of oligosaccharides was described which selectively increased the growth of Bifidobacterium e Lactobacillus- they are a specific sub-group of MACs. These 'canonical' prebiotics are polysaccharides (fructo- and galacto-oligosaccharides) of different lengths, which modify the composition of the intestinal microbiota.
- short-chain fatty acids (SCFA extension) - the main end products of bacterial fermentation, which represent a fantastic example of mutualism between humans and their bacterial symbionts - in turn are formed from MACs. SCFAs, via intestinal receptors, send 'signals' to the central nervous system. With the aim of modulating energy homeostasis (i.e. the correct physiological metabolism of carbohydrates and lipids) and suppressing inflammatory signals.
The two most important SCFAs, butyrate and propionate, could even epigenetically influence host gene expression. The state of energy balance of an individual is therefore 'controlled' by signals mediated by the SCFA, which are produced by intestinal bacteria.
The concept of prebioticit has been expanded in recent times thanks to technological advances that allow the analysis of microbial responses to diet components .The list of prebiotic candidates therefore now includes, for example, molecules of polysaccharides not present in the diet, polyunsaturated fatty acids such as linoleic acid, phytocompounds and phenolic compounds.
Polyphenolsthey 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 the human microbiota, and in preclinical and clinical studies with diets rich in polyphenols.
The polyphenols of green and black tea, studied in-vitro on intestinal microbiota samples, showed the ability to significantly increase the abundance of Bifidobacterium e Lactobacillus, as well as improving the production of SCFA.
They are rich in polyphenols theextra virgin olive oiland some fruits, like citrus fruits e the pomegranate.
High levels of fatin the diet, on the other hand, they negatively alter the composition of the microbiota, especially the bacterial population of the small intestine which has recently proved highly sensitive to the load of fat (and more generally to the digestive processes and the absorption of lipids).
The primary bile acids, produced in the liver by cholesterol and secreted in the small intestine to facilitate the solubilization and absorption of dietary lipids, are in fact modified by the microbiota through hydroxylation (i.e. by inserting hydroxyl groups).
- bile acidsmodified in the intestine act as signaling molecules (in ways similar to SCFAs). The intestinal microbiota - by modifying 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 in the development and prevention of metabolic disease.
Le proteinin turn, they modulate the microbial composition, as amino acids supply essential carbon and nitrogen to intestinal microbes. The contribution of amino acids in total SCFA production is unclear and other molecules that are formed from amino acid metabolism (e.g. indoles, phenols, ammonia and amines) could also affect human health both positively and negatively.
Tryptophan- amino acid that abounds in milk and dairyi, sesame and sunflower, peanuts, eggs, oat - is used by gut 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 (induced experimentally in animal models). And indole-3-acetate, which has recently been shown to reduce inflammation in hepatocytes and macrophages.
Carnitine, an amino acid that is abundant in meat, conversely leads to the formation of a 'negative' metabolite, trimethylamine oxide (TMAO). High levels of TMAO are predictive of cardiovascular events, as well as being implicated in development of fatty liver.
Conclusions and perspectives
The Mediterranean dietit is undoubtedly ideal for promoting a healthy and stable microbiota. A high fiber dietand carbohydrates, with an abundance and variety of vegetables and fruits and a moderate intake of animal proteins. In line, among other things, with the model of ' Healthy diets from sustainable food systems'recently proposed on Lancetby a commission of experts with multi-disciplinary skills.
Characterization of the 'healthy microbiome'it is still extremely complex due to functional redundancies and taxonomic profiles (the diversity of living organisms), which can lead to microbial ecosystems with similar behaviors. It is therefore necessary to carry out research, which must also consider lifestyles and socio-environmental contexts.
The 'discovery' of the microbiotaintestinal 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 recent years of publications on the subject. At the same time awakening industrial interest in the prebiotic and probiotic market, with a further stimulus for research.
THEholobiont human ('the host plus of all its microbial symbionts, including transient and stable members') is progressively understood and his relationship with the guest and his state of health and / or illness are increasingly characterized. The efforts to standardize the preparation of samples and analytical protocols, and the increase of international projects, will allow more and more to elucidate the still obscure points.
Some projectsco-funded by the European Union - such as MetaHIT, which searches for an association between genes expressed by the microbiota and the state of health of the host, as in the case of IBD ( Inflammatory bowel disease), or METAMAPPER, which will investigate the role of the microbiota in inflammatory processes and in the etiology of obesity of cardiovascular and neurodegenerative diseases - will offer further stimuli.
Paola Palestini and Dario Dongo
REFERENCES
'The Lancet Commissions Food in the Anthropocene: the EAT – Lancet Commission on healthy diets from sustainable food systems'(2019). Lancet, http://dx.doi.org/10.1016/S0140-6736(18)31788-4
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Holly A. Swain Ewald and Paul W. Ewald, (2018). 'natural selection, the Microbiome, and Public Health'. Yale Journal of Biology and Medicine 91, 445-455.
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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.He 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.
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.
