Severe acute malnutrition (SAM) constitutes the leading risk for childhood mortality world-wide. Butyrate, a critical metabolite for mucosal immunity produced by anaerobic gut mi-crobes, has been found to be dramatically depleted in children experiencing fatal outcomes related to SAM. However, the association between butyrate depletion and gut microbiota al-teration has not yet been fully explored. Here, we performed a large group-matched case-control study in children aged 0-59 months in Mali. We compared faecal short-chain fatty acids (SCFAs) and gut microbiota from children with SAM and healthy controls, using gas chromatography-mass spectrometry and 16S rRNA v3v4 gene amplicon sequencing. A total of 253 children, including 143 with SAM and 110 controls, were included. Our findings revealed a dramatic imbalance in gut microbiota characterised by the predominance of aerotolerant micro-organisms in children with SAM, irrespective of age and sex. Importantly, aerointolerant species were totally absent in eight samples from children with SAM. A pronounced depletion of faecal valeric, butyric, propanoic and, to a lesser extent, acetic acid was observed, correlating with a ten-fold decrease in butyrate-producing microbes among the SAM population. This notable depletion of gut aerointolerant prokaryotes and butyrate levels persisted without being reversed at the time of discharge. Future therapeutic strategies aimed at addressing SAM should focus on restoring the gut anaerobic microbiota and faecal propionate and butyrate.

The authors have declared no competing interest.

This work was funded by ANR-15-CE36-0004-01 and by ANR Investissements d avenir, Mediterranee Infection 10-IAHU-03 and was also supported by the Region Pro-vence-Alpes-Cote d Azur. This work received financial support from the Mediterranean Infection Foundation.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics Committee of the University of Bamako Faculty of Medicine and Odon-to-Stomatology waived ethical approval for this work on 22 May 2014 (2014/46/CE/FMPOS). Informed and signed consent was obtained from all legal representatives (parents).

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