Gut microbiota role in dietary protein metabolism and health-related outcomes: The two sides of the coin

Background: Human gut bacteria can synthesize proteinogenic amino acids and produce a range of metabolites via protein fermentation, some known to exert beneficial or harmful physiological effects on the host. However, the effects of the type and amount of dietary protein consumed on these metabolic processes, as well as the effects of the microbiota-derived amino acids and related metabolites on the host health are still predominantly unknown. Scope and approach:This review provides an up-to-date description of the dominant pathways/genes involved in amino acid metabolism in gut bacteria, and provides an inventory of metabolic intermediates derived from bacterial protein fermentation that may affect human health. Advances in understanding bacterial protein fermentation pathways and metabolites generated at a global level via the implementation of ‘omics’ technologies are reviewed. Finally, the impact of dietary protein intake and high-protein diets on human health is discussed. Key findings and conclusions:The intestinal microbiota is able to synthesize amino acids, but the net result of amino acid production and utilization, according to dietary patterns still needs to be determined. The amount of ingested dietary protein appears to modify both the diversity and composition of the intestinal microbiota as well as the luminal environment of the intestinal epithelium and peripheral tissues. The understanding of the consequences of such changes on the host physiology and pathophysiology is still in an early stage but major progress is expected in the near future with the investigation of host-microbe omics profiles from well-controlled human intervention studies.This works is supported by the European Union's Seventh Framework Program under the grant agreement no 613979 (MyNewGut).Peer reviewe

Gut microbiota, diet, and obesity-related disorders - The good, the bad, and the future challenges

Diet has been shown to be a major factor in modulating the structure of the mammalian gut microbiota by providing specific nutrient sources and inducing environmental changes (pH, bile acids) in the gut ecosystem. Long-term dietary patterns and short-term interventions have been shown to induce changes in gut microbiota structure and function, with several studies revealing metabolic changes likely resulting from the host microbiota cross-talk, which ultimately could influence host physiology. However, a more precise identification of the specific dietary patterns and food constituents that effectively modulate the gut microbiota and bring a predictable benefit to the host metabolic phenotype is needed to establish microbiome-based dietary recommendations. Here, we briefly review the existing data regarding gut microbiota changes induced by different macronutrients and the resulting metabolites produced via their respective fermentation, including their potential effects on obesity and associated metabolic disorders. We also discuss major limitations of current dietary intervention studies as well as future needs of applying cutting-edge “omic” techniques and of progressing in functional microbiota gene discovery to establish robust causal relationships between the dietary microbiota induced changes and metabolic health or disease.This works is supported by the European Union’s Seventh Framework Program under the grant agreement no 613979 (MyNewGut) and grant AGL2014-52101-P from the Spanish Ministry of Economy and Competitiveness (MINECO, Spain). The FPU scholarship of V. Cerrudo from MECD (Spain) is fully acknowledged.Peer reviewe

NOD1 deficiency promotes an imbalance of thyroid hormones and microbiota homeostasis in mice fed high fat diet

The contribution of the nucleotide-binding oligomerization domain protein NOD1 to obesity has been investigated in mice fed a high fat diet (HFD). Absence of NOD1 accelerates obesity as early as 2 weeks after feeding a HFD. The obesity was due to increases in abdominal and inguinal adipose tissues. Analysis of the resting energy expenditure showed an impaired function in NOD1-deficient animals, compatible with an alteration in thyroid hormone homeostasis. Interestingly, free thyroidal T4 increased in NOD1-deficient mice fed a HFD and the expression levels of UCP1 in brown adipose tissue were significantly lower in NOD1-deficient mice than in the wild type animals eating a HFD, thus contributing to the observed adiposity in NOD1-deficient mice. Feeding a HFD resulted in an alteration of the proinflammatory profile of these animals, with an increase in the infiltration of inflammatory cells in the liver and in the white adipose tissue, and an elevation of the circulating levels of TNF-α. In addition, alterations in the gut microbiota in NOD1-deficient mice correlate with increased vulnerability of their ecosystem to the HFD challenge and affect the immune-metabolic phenotype of obese mice. Together, the data are compatible with a protective function of NOD1 against low-grade inflammation and obesity under nutritional conditions enriched in saturated lipids. Moreover, one of the key players of this early obesity onset is a dysregulation in the metabolism and release of thyroid hormones leading to reduced energy expenditure, which represents a new role for these hormones in the metabolic actions controlled by NOD1.This work was supported by Grants SAF2017-82436R, AGL2017-88801-P and SAF2016-75004R from MINECO/AEI/FEDER/EU, S2017/BMD-3686 from Comunidad de Madrid, CIVP18A3864 from Fundación Ramón Areces and CIBERCV and CIBERHED (funded by the Instituto de Salud Carlos III) and Fondos FEDER.Peer reviewe

Towards microbiome-informed dietary recommendations for promoting metabolic and mental health: opinion papers of the MyNewGut project

The gut microbiota coexists in partnership with the human host through adaptations to environmental and physiological changes that help maintain dynamic homeostatic healthy states. Break-down of this delicate balance under sustained exposure to stressors (e.g. unhealthy diets) can, however, contribute to the onset of disease. Diet is a key modifiable environmental factor that modulates the gut microbiota and its metabolic capacities that, in turn, could impact human physiology. On this basis, the diet and the gut microbiota could act as synergistic forces that provide resilience against disease or that speed the progress from health to disease states. Associations between unhealthy dietary patterns, non-communicable diseases and intestinal dysbiosis can be explained by this hypothesis. Translational studies showing that dietary-induced alterations in microbial communities recapitulate some of the pathological features of the original host further support this notion. In this introductory paper by the European project MyNewGut, we briefly summarize the investigations conducted to better understand the role of dietary patterns and food components in metabolic and mental health and the specificities of the microbiome-mediating mechanisms. We also discuss how advances in the understanding of the microbiome's role in dietary health effects can help to provide acceptable scientific grounds on which to base dietary advice for promoting healthy living

Species-level resolution of 16S rRNA gene amplicons sequenced through the MinION™ portable nanopore sequencer

Background: The miniaturised and portable DNA sequencer MinION™ has been released to the scientific community within the framework of an early access programme to evaluate its application for a wide variety of genetic approaches. This technology has demonstrated great potential, especially in genome-wide analyses. In this study, we tested the ability of the MinION™ system to perform amplicon sequencing in order to design new approaches to study microbial diversity using nearly full-length 16S rDNA sequences. Results: Using R7.3 chemistry, we generated more than 3.8 million events (nt) during a single sequencing run. These data were sufficient to reconstruct more than 90 % of the 16S rRNA gene sequences for 20 different species present in a mock reference community. After read mapping and 16S rRNA gene assembly, consensus sequences and 2d reads were recovered to assign taxonomic classification down to the species level. Additionally, we were able to measure the relative abundance of all the species present in a mock community and detected a biased species distribution originating from the PCR reaction using 'universal' primers. Conclusions: Although nanopore-based sequencing produces reads with lower per-base accuracy compared with other platforms, the MinION™ DNA sequencer is valuable for both high taxonomic resolution and microbial diversity analysis. Improvements in nanopore chemistry, such as minimising base-calling errors and the nucleotide bias reported here for 16S amplicon sequencing, will further deliver more reliable information that is useful for the specific detection of microbial species and strains in complex ecosystems.Authors thank the European 7th Framework Programme for funding ABP and KP, who were supported by the EC Project no. 613979 (MyNewGut)Peer reviewe

Quantity and source of dietary protein influence metabolite production by gut microbiota and rectal mucosa gene expression: a randomized, parallel, double-blind trial in overweight humans

Background: Although high-protein diets (HPDs) are frequently consumed for body-weight control, little is known about the consequences for gut microbiota composition and metabolic activity and for large intestine mucosal homeostasis. Moreover, the effects of HPDs according to the source of protein need to be considered in this context.Objective: The objective of this study was to evaluate the effects of the quantity and source of dietary protein on microbiota composition, bacterial metabolite production, and consequences for the large intestinal mucosa in humans.Design: A randomized, double-blind, parallel-design trial was conducted in 38 overweight individuals who received a 3-wk isocaloric supplementation with casein, soy protein, or maltodextrin as a control. Fecal and rectal biopsy-associated microbiota composition was analyzed by 16S ribosomal DNA sequencing. Fecal, urinary, and plasma metabolomes were assessed by (1)H-nuclear magnetic resonance. Mucosal transcriptome in rectal biopsies was determined with the use of microarrays.Results: HPDs did not alter the microbiota composition, but induced a shift in bacterial metabolism toward amino acid degradation with different metabolite profiles according to the protein source. Correlation analysis identified new potential bacterial taxa involved in amino acid degradation. Fecal water cytotoxicity was not modified by HPDs, but was associated with a specific microbiota and bacterial metabolite profile. Casein and soy protein HPDs did not induce inflammation, but differentially modified the expression of genes playing key roles in homeostatic processes in rectal mucosa, such as cell cycle or cell death.Conclusions: This human intervention study shows that the quantity and source of dietary proteins act as regulators of gut microbiota metabolite production and host gene expression in the rectal mucosa, raising new questions on the impact of HPDs on the large intestine mucosa homeostasis