Abstract
Background/objectives
High salt intake has been linked to several diseases including obesity and an increased risk of death; however, fecal salinity and the ability of salt to alter the gut microbiota, which was recently identified as an instrumental factor for health and disease, remains poorly explored.
Methods/subjects
We analyzed the fecal samples of 1326 human individuals for salinity by refractometry, 572 for gut microbiota by culturomics, and 164 by 16S rRNA-targeted metagenomics. Geographical origin, age, gender, and obesity were tested as predictors of fecal salinity and halophilic diversity. All halophilic isolates were characterized by taxonogenomics and their genome sequenced.
Results
Fecal salinity was associated with obesity independently of geographical origin, gender, and age. The first 2 human-associated halophilic archaeal members were isolated along with 64 distinct halophilic species, including 21 new species and 41 known in the environment but not in humans. No halophiles grow in less than 1.5% salinity. Above this threshold, the richness of the halophilic microbiota was correlated with fecal salinity (r = 0.58, p < 0.0001). 16S metagenomics linked high fecal salinity to decreased diversity (linear regression, p < .035) and a depletion in anti-obesity Akkermansia muciniphila and Bifidobacterium, specifically B. longum and B. adolescentis. Genomics analysis suggested that halophilic microbes are not only transient passengers but may be residents of the human gut.
Conclusions
High salt levels are associated with alteration of the gut microbial ecosystem and halophilic microbiota, as discovered during this study. Further studies should clarify if the gut microbiota alterations associated with high salt levels and the human halophilic microbiota could be causally related to human disease, such as obesity.
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Acknowledgements
We thank the culturomics team for excellent growing work. We wish to honor here the memory of Professor Ogobara Doumbo, who died during the revision of this paper, who was a collaborator with unequaled human and professional qualities. This work has received financial support from the French Government through the Agence Nationale pour la Recherche (ANR), including the “Programme d’Investissement d’Avenir” under the reference Méditerranée Infection 10-IAHU-03. This work was supported by Région Provence Alpes Côte d’Azur and European funding FEDER PRIMMI (Fonds Européen de Développement Régional - Plateformes de Recherche et d’Innovation Mutualisées Méditerranée Infection). We thank Magdalen Lardiere for English reviewing.
Author contributions:
E.H.S., S.K., B.S. and F.B. analysed salinity, isolated the strains, and described the new halophilic species; D.B., V.M., C.R. and A.L. performed the metagenomics sequencing and bio-informatic analyses; E.I.A., S.K., D.M., O.D. and C.S. collected samples and information from included individuals; M.M., E.I.A. and D.R. wrote the manuscript; M.S., M.M. and E.H.S. analysed the data; J.C.L. supervised the study and D.R. conceived and supervised the study.
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Seck, E.H., Senghor, B., Merhej, V. et al. Salt in stools is associated with obesity, gut halophilic microbiota and Akkermansia muciniphila depletion in humans. Int J Obes 43, 862–871 (2019). https://doi.org/10.1038/s41366-018-0201-3
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DOI: https://doi.org/10.1038/s41366-018-0201-3
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