Over the past five years, the European Union-funded microbiome project MyNewGut, coordinated by Yolanda Sanz (CSIC, Spain), has looked at the gut microbiota’s influence on energy balance, brain development, diet-related diseases and behavior. Now, the project has come to an end and MyNewGut’s main findings and achievements were presented at the MyNewGut Final Conference on 18 October 2018 in Brussels (Belgium).

During its lifespan, MyNewGut brought us new insights into the gut microbiome’s contribution to non-communicable diseases (obesity and metabolic disorders) and mood disorders. Specifically, the project’s investigations focused on: 1) How the human microbiome contributes to nutrient metabolism and energy balance; 2) Microbiome-related features that favor or prevent obesity and related metabolic conditions; 3) The close interactions between nervous, metabolic and immune system development in early life (and the long-term health consequences); and 4) The influence of gut microbiome-targeted dietary interventions on reducing disease risk.

As a general overview, the following paragraphs summarize the project’s take-home messages.

The gut microbiome is a key regulator of host metabolism. Bacterial metabolites are relevant factors involved in mediating the complex interactions between gut microbes and host cells. Among them, short-chain fatty acids (acetate, propionate and butyrate) act either locally in the gut or systemically in the brain to regulate food intake via the gut-brain axis. Other microbial metabolites that affect energy homeostasis include branched chain amino acids, bile acids, indole propionic acid and endocannabinoids. Mechanistic studies in mice have revealed that bacterial dipeptidyl peptidase-4-like activity, which is an enzyme involved in the degradation of enteroendocrine hormones produced in the gut, is a new mechanism by which the gut microbiota regulates host appetite and glucose homeostasis.

MyNewGut researchers specifically looked into the role played by dietary proteins, fats and fibers in relation to the gut microbiota. Although possibly helpful for short-term weight loss and beneficial to some aspects of metabolic health, high-protein diets might not be ideal in the long term due to their impact on gut microbiota. Some caution is therefore required for their long-term utilization, as the researchers found that high protein intake increased protein fermentation in the large intestine, generating certain toxic bacterial metabolites related to diseases such as colorectal cancer. Importantly, the protein source in the diet (animal or plant sources) determines in part how the quality of a high-protein diet affects not only the fecal metabolome and gut homeostasis, but also the host urinary metabolome, with possible effects on kidney disease risk.

A high-fat diet may have a negative influence on both the gut microbiota and the brain. It was found in animal models that a high-fat diet can modulate the gut-brain axis through the gut microbiota. A diet rich in saturated fatty acids has detrimental effects on the gut microbiota-characterized by lower diversity in terms of gut microbial species-and negatively influences brain function, inducing depressive-like behavior. A novel gut microbiota-leptin-brain network of relevance to diet-dependent behavioural disorders has been identified by MyNewGut partners. In contrast, diets rich in omega-3 or omega-6 polyunsaturated fatty acids do not seem to have a negative effect on the gut microbiota. In line with these observations, MyNewGut partners showed that Bifidobacterium pseudocatenulatum CECT 7765 reduces depressive-like behaviors associated with obesity in preclinical trials. On the other hand, Bifidobacterium longum 1714 was shown to improve resilience to stress (a major risk factor for depression), improving adverse effects, for example, on sleep quality  in healthy volunteers.

Diets high in fiber are associated with lower rates of depression, they help to maintain body weight and reduce the risk of developing chronic metabolic diseases. We have just started to understand the gut microbiome’s contribution when explaining why a diet  rich in fiber is good for us, from reducing the risk of developing diabetes and heart disease to a lower risk of all-cause mortality. The MyNewGut project has yielded some important new clues about the fiber’s role in human health and the way it delivers many of its benefits to the trillions of bacteria in our gut, while the researchers also considered how can we use this knowledge to prevent diseases. A large clinical intervention trial with a fiber combination showed benefits on cardio-metabolic disease risk markers, reducing systolic and diastolic blood pressure in humans. Accumulated evidence from both observational and intervention studies reviewed by MyNewGut also indicated that the Mediterranean dietary pattern (or modifications of it) based on grains and fiber, fish and fermented foods, alongside regular aerobic exercise, could help prevent depression and non-communicable diseases.

Finally, specific gut microbial strains could emerge as the next generation of probiotics for tackling obesity. This is the case, for example, of Bacteroides uniformis CECT 7771, which contributes to restoring obesity-related metabolic and immune dysfunction in mice.

You can access the scientific publications, including in vitro, animal and human studies led by MyNewGut researchers over the last 5 years, here.

Although the MyNewGut project has come to an end, the microbiome research continues with two new H2020 EU-funded projects: MicrobiomeSupport: Towards coordinated microbiome R&I activities in the food system to support EU and international bioeconomy goals and the EU Circles research project, aimed at developing microbiome solutions for producing healthier foods through a sustainable food production system.

Altogether, the MyNewGut’s findings currently available support the potential of gut microbiota-targeted therapies in managing diet-related diseases and mood disorders. The project consortium expects to apply research findings from bench to bedside, as a means of developing effective interventions directed at the gut microbiome in order to fight obesity, metabolic syndrome and emotional disorders.