Stool microRNA Profiles Associated With Diet, Gut Microbiome Patterns

Intestinal microbiome, bacteria colonizing different parts of digestive system, Bifidobacterium, Lactobacillus, Enterococcus and Escherichia coli, 3D illustration
Researchers sought to characterize how specific diets are associated with the gut microbiome and how these associations manifest in the gut microbial composition.

Stool microRNA (miRNA) profiles are associated with specific diets, with lipids propelling epigenetic modifications and host-microbial crosstalk in the gut, according to a study recently published in Gut.

Diet and nutrition are associated with risk factors for different diseases, and miRNAs found in stool may directly regulate specific bacterial gene expression and affect gut microbial growth. Researchers sought to characterize how specific diets are associated with the gut microbiome found in the stool of vegans, vegetarians, and omnivores, and how these associations manifest in the gut microbial composition.

In total, 120 participants were included in the study (72 women) and divided into groups based on diet: 40 participants followed an omnivorous diet, 40 a vegetarian diet, and 40 a vegan diet. Small RNA analysis and shotgun metagenomic sequencing were performed on fecal samples. Additionally, participants filled out a food frequency questionnaire (FFQ) to assess their typical diet and lifestyle practices.

Participants who adhered to an omnivorous diet had slightly higher body mass indexes (BMIs) compared with the vegetarian and vegan groups (23.6 kg/m2 vs 21.9 kg/m2 and 21.8 kg/m2, respectively). The same was noted in terms of waist circumference, with participants in the omnivore group having larger circumferences vs the vegetarian and vegan groups (83.8 cm vs 78.1 cm and 78.9 cm, respectively).

A higher intake of vitamin C, β-carotene, and fiber was found in the vegan group compared with the omnivores. The vegan group also consumed less vitamin D, animal protein, retinol, and cholesterol. The vegetarian group was noted to consume fewer polyunsaturated fatty acids compared with the omnivore group.

After sequencing, researchers found that diet was associated with stool microbiomes in the omnivore, vegetarian, and vegan groups, with a median of 253, 321, and 310 stool miRNAs detected in each group, respectively. Further, several miRNAs characterized specific signatures of the different dietary regimens. Forty-nine miRNAs were differentially expressed throughout the omnivore, vegetarian, and vegan groups; 15 of these showed trends of upregulation or downregulation in both the vegetarian and vegan groups compared with the omnivore group. 

Having a significant role in lipid metabolism, miR-636 and miR-4739 expression levels decreased as duration of time adhering to a nonomnivorous diet increased. This occurred independently of age.

In addition, targets of stool miRNAs upregulated in vegetarian/vegan subjects were enriched in both lipid and folate metabolism. Participants in the vegan and vegetarian groups were characterized by high stool levels of miR-425-3p, an miRNA related to lipid metabolism. Participants with the highest levels of miR-425-3p expression, regardless of diet group, showed higher abundance of Akkermansia muciniphila, Roseburia hominis, and Roseburia sp.

In terms of limitations, investigators acknowledge they cannot exclude the possible influence of other cellular components of the gastrointestinal system, such as those originating from the stromal or immune compartments, on study results.

The authors noted their results “show a gradual modulation of the human miRNome as a consequence of different dietary regimens with important modifications in miRNAs involved in lipid and folate metabolism.” “Stool miRNA profiles and microbiome composition, together with dietary nutrients, can accurately distinguish different diets and strengthen the evidence of host-gut microbiome crosstalk,” they concluded.


Tarallo S, Ferrero G, De Filippis F, et al. Stool microRNA profiles reflect different dietary and gut microbiome patterns in healthy individuals. Gut. Published online July 27, 2021. doi: 10.1136/gutjnl-2021-325168