Microcella aerolata GA224 exhibits preventive potential against Streptococcus pneumoniae infection via the gut-lung axis.

Abstract

Antibiotics and vaccines have long been major key interventions against Streptococcus pneumoniae (Spn) infection. However, alternative therapies are urgently needed with the original therapies becoming suboptimal efficacy. A beneficial bacterium, Microcella aerolata strain GA224, with protective potential against Spn infection was isolated in previous study. Here, this protective effect was investigated at the bacterial, cellular and animal levels, exploring the mechanisms from the perspective of the gut-lung axis. Cellular and animal models of Spn infection were established and GA224 was administered for prevention or treatment. Spn adherence, inflammatory gene expression, histopathological features, gut microbial profiles and fecal metabolomic signatures were examined. In vitro, GA224 inhibited Spn growth with a bacteriostatic diameter of 16 mm and reduced adherence by 83.4% (P < 0.01) in prevention groups, while suppressing inflammatory gene expression (IL-1β, IL-6, TNF-α) by 40-50% (P < 0.001) in Spn-infected cells. In Spn-infected rats, GA224 intranasal administration improved body weight gain by 8.2% (vs. Tre group + 3.7%, P < 0.05) and reduced lung injury score by 25% (P < 0.01). In addition, GA224 administration alleviated dysbiosis of the gut microbiota, including declined abundance of Ruminiclostridium and Roseburia, increased abundance of Ruminococcus and restricted out-migration of infectious bacteria. In terms of the fecal metabolism, differential metabolites and disordered metabolic pathways were altered by GA224, including glycine, serine and threonine metabolism and pentose and glucuronate interconversion. Intestinal bacteria showed multiple correlations with fecal metabolites with strongest correlation founding between Ruminococcus and oxidized phospholipids. Notably, Anaerotaenia (r = -0.67 with LysoPC), Ruminiclostridium (positively correlated with lung coefficient, r = 0.62) and Ruminococcus (strongest correlation with oxidized phospholipids, r = 0.8) demonstrated microbiota-metabolite interactions potentially mediating gut-lung axis regulation.Finally, we demonstrate that M. aerolata GA224 provided a protective potential against Spn infection. In addition to the inhibition in adherence and inflammation, remodeling gut microbiota and improving metabolism via the gut-lung axis may be the critical avenue to this protective effect.