The process of aging predisposes to hepatic functional and structural impairment leading to inflammation – called inflammageing – and favours non-alcoholic fatty liver disease. Spirulina is a cyanobacterium within the Oscillatoraceae family, which is used as a food additive. Previous studies suggest the beneficial effects of Spirulina on immune functions and against non-alcoholic fatty liver disease, inflammatory disorders, hyperglycaemia and hypercholesterolaemia in mouse models of metabolic syndrome. The aim of the present study was to test the potential hepatoprotective effects of Spirulina extract supplementation in aged mice and to determine whether these effects can be related to a modulation of the gut microbiota.

Male C57Bl6J mice of 3- and 24-months old were fed a control diet supplemented with or without 5% Spirulina extract (Biores, Belgium) during 8 weeks.

Aged mice exhibited inflammation and oxidative stress in the liver tissue (higher expression of TNF-, IL-6, IL-1beta, MCP-1, CD68, COX-2, CD11c, TLR4, NADPH oxidase) as compared to mice of 3 months. The supplementation with Spirulina extract reduced those hepatic inflammatory and oxidative markers in 24-months mice. Interestingly, the expression of transcription factor involved in immune system regulation (FoxP3 in T regulatory cells) and the expression of antimicrobial peptide (Reg3gamma) were upregulated in the ileum of Spirulina-treated mice. Combination of pyrosequencing and qPCR analyses of the 16S rRNA gene revealed a decrease in total bacteria and – among specific changes of gut microbiota composition – an increase in lachnospiraceae population by Spirulina treatment.

Our study shows for the first time that the oral administration of a cyanobacterium (Spirulina) is able to modulate the gut microbiota, to activate immune system in the gut, thereby improving hepatic inflammation in aged mice. Those data allow envisaging new therapeutic tools, based on gut microbes–host interactions, in the management of systemic diseases, such as non-alcoholic fatty liver disease.