Project description:The objective of this study was to evaluate the impact of dietary Spirulina and lysozyme supplementation over the muscle proteome of piglets during the post-weaning stage. Thirty piglets were randomly distributed among three diets: control (no microalga), SP (10% Spirulina) and SP+L (10% Spirulina + 0.01% lysozyme). They were fed ad libitum for 4 weeks, after which they were sacrificed and samples of the longissimus lumborum muscle were taken. The muscle proteome was analysed using a Tandem Mass Tag (TMT)-based quantitative approach.
Project description:<p>Background & Aims:</p><p>Spirulina, a microalgae renowned for its nutrient density, shows promise in modulating glucose and lipid metabolism. However, its efficacy and underlying mechanisms against metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear. We hypothesized that spirulina exerts its hepatoprotective effects by reshaping the gut microbiome and its associated metabolome.</p><p>Methods:</p><p>We conducted an 8-week pilot study in 23 patients with MASLD receiving spirulina supplements (1g TID), assessing changes in liver fat, enzymes, and metabolic parameters. To establish causality and elucidate mechanisms, we employed two distinct murine models of steatohepatitis: a Western diet model and a choline-deficient diet model. Interventions included spirulina gavage, antibiotic-induced microbiota depletion, fecal microbiota transplantation (FMT), and administration of the microbial metabolite 2-hydroxy-3-methylbutyrate (2H3MB). Multi-omics approaches (16S rRNA sequencing, metabolomics, single-cell RNA sequencing) and flow cytometry were utilized.</p><p>Results:</p><p>Spirulina supplementation significantly alleviated hepatic steatosis in both human subjects and murine models. This was accompanied by a restoration of gut microbial ecology, characterized by enriched beneficial genera (e.g., Akkermansia, Bacteroides, Blautia). Metabolomic profiling identified a marked increase in the gut microbiota-derived metabolite 2H3MB in the feces and liver. Critically, the protective effects of spirulina were abolished in microbiota-depleted mice and could not be transferred via FMT from spirulina-treated donors to naïve recipients, indicating a dependency on an intact and active microbiome. Direct administration of 2H3MB was sufficient to recapitulate the anti-steatotic effects of spirulina in high-fat diet-fed mice. Mechanistically, single-cell RNA sequencing and flow cytometry revealed that 2H3MB reshaped the hepatic immune microenvironment by specifically promoting the M2 polarization of macrophages, which in turn ameliorated lipid accumulation.</p><p><br></p><p>Conclusions:</p><p>Our findings unveil a novel gut-liver axis pathway through which spirulina prevents hepatic steatosis. Spirulina enhances the production of 2H3MB by specific gut microbes, which then signals to the liver to drive an anti-inflammatory, pro-resolutive M2 macrophage polarization, ultimately mitigating lipid deposition. This work highlights gut microbial metabolites, particularly 2H3MB, as promising therapeutic targets for MASLD.</p>
Project description:<p>Background & Aims:</p><p>Spirulina, a microalgae renowned for its nutrient density, shows promise in modulating glucose and lipid metabolism. However, its efficacy and underlying mechanisms against metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear. We hypothesized that spirulina exerts its hepatoprotective effects by reshaping the gut microbiome and its associated metabolome.</p><p>Methods:</p><p>We conducted an 8-week pilot study in 23 patients with MASLD receiving spirulina supplements (1g TID), assessing changes in liver fat, enzymes, and metabolic parameters. To establish causality and elucidate mechanisms, we employed two distinct murine models of steatohepatitis: a Western diet model and a choline-deficient diet model. Interventions included spirulina gavage, antibiotic-induced microbiota depletion, fecal microbiota transplantation (FMT), and administration of the microbial metabolite 2-hydroxy-3-methylbutyrate (2H3MB). Multi-omics approaches (16S rRNA sequencing, metabolomics, single-cell RNA sequencing) and flow cytometry were utilized.</p><p>Results:</p><p>Spirulina supplementation significantly alleviated hepatic steatosis in both human subjects and murine models. This was accompanied by a restoration of gut microbial ecology, characterized by enriched beneficial genera (e.g., Akkermansia, Bacteroides, Blautia). Metabolomic profiling identified a marked increase in the gut microbiota-derived metabolite 2H3MB in the feces and liver. Critically, the protective effects of spirulina were abolished in microbiota-depleted mice and could not be transferred via FMT from spirulina-treated donors to naïve recipients, indicating a dependency on an intact and active microbiome. Direct administration of 2H3MB was sufficient to recapitulate the anti-steatotic effects of spirulina in high-fat diet-fed mice. Mechanistically, single-cell RNA sequencing and flow cytometry revealed that 2H3MB reshaped the hepatic immune microenvironment by specifically promoting the M2 polarization of macrophages, which in turn ameliorated lipid accumulation.</p><p><br></p><p>Conclusions:</p><p>Our findings unveil a novel gut-liver axis pathway through which spirulina prevents hepatic steatosis. Spirulina enhances the production of 2H3MB by specific gut microbes, which then signals to the liver to drive an anti-inflammatory, pro-resolutive M2 macrophage polarization, ultimately mitigating lipid deposition. This work highlights gut microbial metabolites, particularly 2H3MB, as promising therapeutic targets for MASLD.</p>