Diet appears to be a major factor that influences the composition of the human gut microbiota. Dietary proteins are first digested in the small intestine by human digestive enzymes, but about 10–12% reach the large intestine in a regular Western diet. This amount increases proportionally with the amount of dietary protein ingested in the context of high-protein diets. These diets increase satiety, favorably modify lipid metabolism, and facilitate weight management, but may also have deleterious effects on diverse tissues and organs, particularly in the long-term. The metabolic activity of the gut microbiota on protein-derived products, and especially on amino acids, generates numerous metabolites with suspected or established effects on host intestinal physiology, liver and peripheral tissues. Bacterial metabolites produced from protein fermentation include: gases, ammonia, aromatic compounds (phenol, p-cresol, indole), polyamines, fatty acids (butyrate, proprionate, isobutyrate, 2-methylbutyrate), organic acids (formate, lactate, succinate) and compounds with potential neuroactivity (es. GABA, serotonin, histamine, phenethylamine, tyramine, tryptamine).
A high fat diet, especially when rich in saturated fatty acids may have negative effects on the gut microbiota, characterized by a lower number of microbes and a lower variety of microbial species. High-fat diets rich in omega-3 or omega-6 polyunsaturated fatty acids do not seem to negatively affect the microbiota, whereas the effects of monounsaturated fatty acids are less consistent. MyNewGut experts have conducted several human intervention trials to investigate dietary health effects potentially mediated by the microbiota and they are publishing a range of position papers that will show evidence on how we could inform future dietary recommendations. MyNewGut partners have specifically looked into the role played by proteins, fats and fibers on the gut microbiota. MyNewGut partners found out that high protein consumption, which increases protein fermentation in the large intestine, generates some of the toxic metabolites (products of metabolism) linked to diseases such as colorectal cancer.
The MyNewGut project has discovered new bacterial species and strains in healthy people that seem to be effective against obesity, metabolic and mental disorders related to stress and obesity (e.g. depression). They do so by influencing the endocrine and immune pathways that have an impact on both our physical and mental health. The bacterial strain Bacteroides uniformis CECT 7771 has shown pre-clinical efficacy on metabolic and immune dysfunctions in obesity, for example reducing serum triglyceride levels, glucose intolerance and body weight gain as well as inflammation. Bifidobacterium pseudocatenulatum CECT 7765 was shown to reduce depressive-like behavior associated with obesity in pre-clinical trials. A Bifidobacterium longum strain has been demonstrated to have a positive impact on perceived stress, sleep quality and cortisol release in a double-blinded placebo-controlled intervention trial in humans. These strains could potentially be next generation probiotics that could in the future be used to help tackle obesity and depression.
Studies of the MyNewGut partners showed that Western diets rich in saturated fat resulted not only in obesity, but also in depression-like behavior. The depression-like behavior associated with diet-induced obesity depended on the gut microbiome, because the effects were blunted by antibiotic-treatment. In high-fat diet fed mice, using the same mouse model, MyNewGut also showed that a bacterial strain (Bifidobacterium pseudocatenulatum CECT 7765) reduces depressive-like behavior associated with obesity, acting through the gut-brain axis. These results are only a starting point, and new research would have to confirm the findings in humans. Studies in animal models conducted by project partners have revealed new mechanisms whereby the microbiota could impact metabolic health. MyNewGut partners showed that peptidase activity (DPPIV) responsible for the degradation of entero-endocrine hormones produced in the gut, which regulate appetite and glucose homeostasis (like glucagon-like peptide I [GLP-I]), are of bacterial origin. This means that the presence of specific bacteria producing these new enzymes can adversely influence appetite, food intake and body weight gain.
The MyNewGut project has also explored innovative interventions, including Faecal Microbiota Transplants (FMT) for restoring dysbiosis-associated disorders. In FMT, the microbiota of a healthy donor is transferred to an individual suffering from some form of dysbiosis. In MyNewGut studies, the donor’s microbiota was transferred to human subjects with metabolic syndrome. In these studies, the responsiveness to treatment depended on the individual’s gut microbiota profile, suggesting a need for personalized intervention strategies. This study demonstrates that the individual’s microbiota directly impacts neural systems that could mediate the impact of food intake on metabolic health. MyNewGut partners conducted a longitudinal study in children to determine the role of the microbiota, the lifestyle (diet, exercise, etc.) and other individual factors (immune and metabolic profile) in the development of overweight. The study revealed that specific microbiota configurations were indeed correlated to inflammatory markers and dietary patterns, and subsequently to the development of obesity.
Observational and intervention studies show that Westernized diets, high in fat and low in fiber, reduce species diversity, cause a loss of bacteria specialized in fiber fermentation, and increase gut exposure to pro-inflammatory and carcinogenic metabolites in humans. Changes from a rural to a Western diet also result in remarkable reciprocal changes in mucosal biomarkers of cancer risk, supporting the hypothesis that gut microbiota–diet interactions influence vulnerability to disease. Many studies demonstrate that dysbiosis is associated with unhealthy diets and obesity and more recently mood disorders. These studies have indicated that disease can be linked to a number of microbiota features (reduced diversity, richness, etc.), candidate bacterial groups and, to a lesser extent, functional pathways. The research has also discovered that dietary changes which favorably influence the microbiota may have a higher and longer-lasting effect during stages of development, and this emphasizes the importance of diet during early life for long-term health in adulthood.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
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