The synergism of <i>Lactobacillaceae</i>, inulin, polyglucose, and aerobic exercise ameliorates hyperglycemia by modulating the gut microbiota community and the metabolic profiles in db/db mice

Abstract

This study aimed to assess the impact of <i>Lactobacillaceae</i> (L or H represents a low or high dose), inulin (I), and polydextrose (P) combined with aerobic exercise (A) on the composition of the gut microbiota and metabolic profiles in db/db mice. After a 12-week intervention, LIP, LIPA, and HIPA groups exhibited significant improvements in hyperglycemia, glucose tolerance, insulin resistance, inflammatory response, and short-chain fatty acid (SCFA) and blood lipid levels compared to type 2 diabetes mice (MC). After treatment, the gut microbiota composition shifted favorably in the treatment groups which significantly increased the abundance of beneficial bacteria, such as <i>Bacteroides</i>, <i>Blautia</i>, <i>Akkermansia</i>, and <i>Faecalibaculum</i>, and significantly decreased the abundance of <i>Proteus</i>. Metabolomics analysis showed that compared to the MC group, the contents of 5-hydroxyindoleacetic acid, 3-hydroxysebacic acid, adenosine monophosphate (AMP), xanthine and hypoxanthine were significantly decreased, while 3-ketosphinganine, sphinganine, and sphingosine were significantly increased in the LIP and LIPA groups, respectively. Additionally, LIP and LIPA not only improved sphingolipid metabolism and purine metabolism pathways but also activated AMP-activated protein kinase to promote β-oxidation by increasing the levels of SCFAs. <i>Faecalibaculum</i>, <i>Blautia</i>, <i>Bacteroides</i>, and <i>Akkermansia</i> exhibited positive correlations with sphingosine, 3-ketosphinganine, and sphinganine, and exhibited negative correlations with hypoxanthine, xanthine and AMP. <i>Faecalibaculum</i>, <i>Blautia</i>, <i>Bacteroides</i>, and <i>Akkermansia</i> may have the potential to improve sphingolipid metabolism and purine metabolism pathways. These findings suggest that the synergism of <i>Lactobacillaceae</i>, inulin, polydextrose, and aerobic exercise provides a promising strategy for the prevention and management of type 2 diabetes.