Establishing the role of diet in the microbiota-disease axis.

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PubMed ID: 30542085

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Reimer RA

Nat Rev Gastroenterol Hepatol. Feb 2019. doi: 10.1038/s41575-018-0093-7

COMMENT: This work reviews the most important findings about the impact of diet in the demonstrated relationship between gut microbiome and disease, especially focusing to obesity, diabetes and metabolic syndrome.

Evidence that chronic metabolic diseases such as obesity, type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease are associated with alterations in the gut microbiota has increased steadily over the past decade.  

Important findings about the role of diet in modifying the gut microbiome and maintaining intact the intestinal barrier (see figure):

Key mediators of these beneficial health effects seem to be short-chain fatty acids (SCFAs), which are microbial metabolites produced through bacterial fermentation of nondigestible carbohydrates. 

...germ-free mice receiving the high-fibre post-intervention faecal microbiota had markedly lower fasting and postprandial blood glucose levels compared with mice receiving control post-intervention faecal microbiota. 

Diet is an important modifier of the mucosal barrier and can contribute to its deterioration (for example, via a Western-style diet) or fortification (for example, via fermentable carbohydrates in a high-fibre diet). The consequences of intestinal barrier defects might include metabolic disease or ulcerative colitis. 

A Western-style diet high in fats and sugars and low in fibre is associated with metabolic disease and dysbiosis and, as shown by Schroeder and colleagues this year, also contributes to colonic mucus deterioration. Mice fed a Western diet had major increases in the penetrability of the inner colonic mucous layer and reduced mucus growth rate compared with chow-fed mice.

The colonic mucous layer acts as a physical barrier to protect the host from the high bacterial load in the gut. A compromised intestinal barrier is permissive to the translocation of microbial products from the gut into systemic circulation, which can trigger metabolic disease. 

IL-22 mediates the protective effect of high fibre diet:

By restoring IL-22 production, normalizing bacterial growth levels and promoting gut epithelial cell proliferation and antimicrobial gene expression, inulin treatment was able to fortify innate mucosal defenses and protect against low-grade inflammation associated with a high-fat diet. In contrast to enhanced intestinal defenses seen with inulin treatment in wild-type mice, inulin lost its ability to prevent high-fat-diet-induced microbiota encroachment in Il22-knockout mice.

Environmental factors are more important than genetic factors determining the composition of the microbiome:

... the question of whether the environment or host genetics dominate the shaping of the human gut microbiome remains. To answer this question, Rothshild and colleagues7 utilized data from a cohort of 1,046 healthy Israeli individuals from Ashkenazi, North African, Middle Eastern, Sephardi, Yemenite and “admixed/other” ancestry. On the basis of host genotyping and stool metagenomic and 16S ribosomal RNA gene-sequencing analysis, the authors show that genetic ancestry is not significantly associated with microbiome composition 

 Past or present household sharing was more influential for gut microbiome composition than genetic relationship. 


Collectively, these data provide convincing evidence that diet, via changes to the composition of the gut microbiota, affects the intestinal barrier and could be used to better treat or prevent diseases linked to intestinal barrier defects. 

Key advances:

  • Using a high-fibre diet to target short-chain fatty acid producers in the gut microbiota could assist type 2 diabetes management
  • Defects in the mucous layer of mice fed a Western-style diet are mediated by gut bacteria and can be rescued by faecal microbiota transplant from chow-fed mice or by prebiotic or probiotic treatment
  • Environmental factors such as sharing a household play a major part in shaping microbiome composition, with a relatively minor contribution by host genetics

New diet-based personalized interventions using personalized medicine approaches are promising:

This personalized nutrition approach has the potential to increase the efficacy of nutritional interventions to treat disease.


Raquel Tobes