Nutritional Modulation of the Gut Microbiome PDF

Deniz Sertel, PhD. Nutritional modulation of the gut microbiome for metabolic health and healthy longevity Diet modulates the composition and function of the microbiota Gut microbiota responds rapidly to changes in the diet Composition of the gut microbiota is determined by long term dietary...

Deniz Sertel, PhD. Nutritional modulation of the gut microbiome for metabolic health and healthy longevity Diet modulates the composition and function of the microbiota Gut microbiota responds rapidly to changes in the diet Composition of the gut microbiota is determined by long term dietary habits. Different people respond differently to changes in the diet Microbial diversity Diversity is a indicator of a “healthy gut.” Low diversity has been associated with + Obesity + Inflammatory bowel disease + Psoriatic arthritis + Diabetes + Atopic eczema + Coeliac disease Effects of dietary components Carbohydrate, fat, protein, and others Carbohydrate The effects of carbohydrate on gut microbiota depends on the chemical structure + Can it reach the colon without digestion + Can the host use the carbohydrate as energy source Carbohydrates that can reach the colon are; + Polysaccharides other than starch + Resistant starch + Oligosaccharides (Polyols can also reach the colon with out digestion and absorbtion in the small intestine)  High sugar diets = gut microbiota dysbiosis Microbial diversity Lactobacillus, and others Weight gain Clostridia Firmicutes: Bacteriodetes ratio Dietary fiber Edible carbohydrate polymers with three or more monomeric units Resistant to the endogenous digestive enzymes and thus are neither hydrolysed nor absorbed in the small intestine Some are fermentable (used by the gut microbes) Fermentation of dietary fibre is one of the dominant functions of the caecal and colonic microbiota and a major source for SCFAs, which are the fermentation end products. Dietary fibre has been associated with + Improved glucose tolerance + Reduced insulin resistance + Reduced weight gain + Improved intestinal barrier function (protection against pathogens) + Increased SCFAs-producing microbiota + Increased microbial diversity Short chain fatty acids SCFAs -- energy source & signal molecules Butyrate main energy source for colonocytes Can induce apoptosis in cancer cells Glucose and energy homeostasis Regulate gut hormones Oxygen balance Antiinflammatory Propionate Regulates gluconeogenesis (in the liver) Regulate gut hormones Antiinflammatory Energy source Acetate Most abundant SCFA Higher production of SCFAs correlates with Essential for microbial growth - Reduced weight gain Cholesterol metabolism and lipogenesis Central appetite regulation - Reduced insulin resistance Energy source Interactions between the diet and the gut microbiota dictate the production of short-chain fatty acids.  Fat High intake of dietary fat was thought to be associated with CVDs and obesity and therefore discouraged for decades Association was not confirmed by a meta analysis of prospective studies published between 1981 and 2007 [(Siri- Tarino, P. W., Sun, Q., Hu, F. B. & Krauss, R. M. Meta- analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease. Am. J. Clin. Nutr. 91, 535–546 (2010)]. Recent dietary guidelines do not recommend a reduction in total fat intake but underline the importance of optimizing the types of fat in diet  İncrease in weight gain Increase in LPS Elevated levels adiposity, Diet rich in fat expressing of LPS in the elevation of bacteria circulation inflammatory markers, increased gut permeability But the type of the fat matters Animal studies have shown; + Saturated fat – increase in Bacteroides, Turicibacter and Bilophila spp– promote inflammation, adiposity, insulin insensitivity + Unsaturated fat – increase in Bifidobacterium, Akkermansia and Lactobacillus spp – no metabolic impairment + The disruptive effect of fat on the microbiome can be transferred to the offspring Available evidence suggests that saturated fat modifies the microbiome to promote detrimental effects that are partially inheritable, resulting in context- specific risk of the metabolic syndrome, colitis or central nervous system autoimmunity. high fat diets and saturated fat and trans fats should be avoided, while MUFAs and omega-3 PUFAs should be encouraged in order to regulate gut microbiota and inflammation towards promoting control of body weight/fat Additional studies, especially in humans, are required to resolve conflicting reports Bile acid metabolism Bile acids (BA) are amphipathic molecules synthesized in the liver from cholesterol, which are stored in the gallbladder and released into the small intestine after food intake. one of their major functions is to facilitate the emulsification of dietary fats and to assist the intestinal absorption of lipids and lipophilic vitamins There is a strong biochemical relationship between BAs and gut microbiota gut microbiota in can convert conjugated BAs into free BAs, and can transform BAs into secondary BAs reduce blood cholesterol by affecting the enterohepatic circulation of BAs Gut microbiota affects the metabolism of BAs by regulating the activity of BSH to reduce LDL cholesterol levels BAs have bacteriostatic properties and an antimicrobial effect BAs also prevent bacteria from overgrowth and decrease inflammation Protein Red and processed meat are commonly associated with an increased risk of developing CVD. Choline, betaine, and L-carnitine ► by gut microbiota ► trimethylamine (TMA) ► by liver ► trimethylamine N- oxide (TMAO) TMAO is associated with promoting atherosclerosis risk of thrombosis and CVDs Meat and diary product consumption increase trimethylamine production (Red meat is specifically rich in L –carnitine) In both mice and humans, Prevotella spp were associated with the ability to transform l -carnitine to TMA or TMAO.  BCAAs are essential amino acids that cannot be synthesized in the human body and are obtained from food, including leucine, isoleucine, and valine Red meat and dairy products are rich in BCAAs and synthesized by intestinal bacteria such as Enterococcus, Enterobacter, Bifidobacterium, and Clostridium botulinum BCAAs are associated with insulin resistance Studies in mice have shown that Parabacteroides merdae degrades BCAAs and protects against obesity-related atherosclerosis. Aromatic amino acids including tyrosine, tryptophan, and phenylalanine are metabolized into indole and phenols by certain intestinal anaerobic bacteria, such as Bacteroidetes, Lactobacillus, Bifidobacterium, Clostridium, and Peptostreptococcus indole propionic acid is associated with insulin sensitivity and appears to reduce the risk of diabetes Indolepropionic acid produciton increases with dietary fibre consumption  Gut microbiota metabolizes dietary tryptophan to indoxyl, which further generates indoxyl sulfate through sulfonation. Excessive accumulation of indoxyl sulfate causes cardiomyocyte damage and increases thrombus formation Another phenol compound, 4-methylphenol, can inhibit the differentiation of 3T3-L1 preadipocytes into mature adipocytes, induce apoptosis and reduce glucose uptake Sulfur-containing amino acids such as cysteine and methionine produce sulfides under the action of intestinal bacteria, which are mainly produced by the desulfurization reaction of intestinal bacteria Studies have found that bacteria such as Escherichia coli, Salmonella, Clostridium and Enterobacter aerogenes in the large intestine can lyse sulfur- containing amino acids Some bacteria in the human intestine use sulfate as a substrate to produce a large amount of H2S, which has various functions such as protecting cells, relaxing blood vessels, regulating blood pressure and reducing heart rate. And H2S is also important in the protection of CVDs Protein source or type impact gut microbiota composition, given that the amino acid composition differs between types. A 14-day feeding trial in rats fed either protein from soy, pork, beef, chicken, fish and casein, (the latter served as a control) revealed changes by day 2 particularly between red meat (pork and beef) and white meat (fish and chicken). Principal component analysis revealed distinct microbiota on days 7 and 14, whereby the soy protein group was separate from the meat and casein groups. In another similar study, soy protein was associated with increased faecal SCFAs in rats compared to rats fed white meat, red meat or casein. The soy group also had a higher relative abundance of Bacteroides and Prevotella which are the major propionate and other SCFA producers. Lactobacillus, a genus known for its beneficial effects was increased in the gut microbiota by ingestion of meat proteins. In this study, the diets clustered into two subgroups at the phylum level, the ‘meat class’ and the ‘non-meat class.’ In another study, soy fed hamsters were found to have a more consistently diverse microbiota in the small and lower intestine compared to hamsters fed milk protein isolate and the largest differences were found within the Bacteriodetes phylum  Processed meat has been associated with colorectal cancer risk in humans owing to the production of carcinogenic heterocyclic amines Experimental evidence suggets that Lactic- acid-producing bacteria (such as Lactobacillus) can directly bind heterocyclic amines and therefore potentially protect the host from the induction of DNA damage and neoplasia High protein diets are generally associated with decreased body weight and improvement in blood metabolic parameters but they also modify various bacterial metabolites and co-metabolites in faecal and urinary contents. The effects of high protein diets on the gut microbiota were dependent on protein source (plant versus animal). Low protein diets have been shown to be beneficial in certain risk groups and patients Specific members of the gut microbiota might protect against or mediate the health consequences of metabolites associated with red and processed meat consumption, although many of these associations lack a proof of causation and further studies are needed. Artificial Sweeteners Sucralose, aspartame and saccharin disrupts the diversity and balance of colon microbiota Animal studies have shown that consumption of sweeteners have negative impact: Bacteroides Clostridia Induced glucose intolerance Proteobacteria Fecal pH Food additives Emulsifiers are commonly present in processed food Animal studies show that emulsifiers (carboxymethylcellulose and polysorbate-80) promote a dysbiotic microbiota which induces low- grade inflammation, metabolic syndrome and colitis Proteobacteria Microbial diverstiy Bacteroidales and Verrucomicrobia Restrictive diets Vegan or vegetarian diets + plant-based diet may be an effective way to promote a diverse ecosystem of beneficial microbes that support overall health, but further research is required Raw food + Risk of infections Gluten free + Beneficial for people with gluten sensitivity or coeliac disease + Can increase the risk of heart disease in people without gluten intolerance or coeliac disease FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) + Low FODMAP diet reduced symptoms of irritable bowel syndrome  Long-term dietary habits affect the quality of gut microbiota In general healthy eating patterns include ; + a rich source of dietary fibre + healthy fats (MUFAs and PUFAs) + trend towards more plant-derived proteins Take home messages Quality and quantitiy matters Less is more Balance is the key Fibre is an important nutrient for a healthy microbiome + Although beneficial effects of dietary fibre has been shown in various studies, these effects are related with the dose,other components of the diet, the enterotype and host genetics etc Restrictive diets should be applied in caution No diet can «rule them all» Optimal diet should be tailored to the individual’s needs, taking into account the gut microbiota.