Modulation of sepsis by Lacticaseibacillus rhamnosus and the potential role of short-chain fatty acid levels in feces and blood.

Administration of live L. rhamnosus strains fa1 and fg2 prior to surgery effectively reduced sepsis severity, but heat-killed probiotics did not.

• Probiotic administration was performed prior to cecal ligation and puncture (CLP) surgery in mice.
• Both fa1 and fg2 strains showed efficacy in reducing sepsis severity.
• Heat-killed versions of the same probiotic strains failed to attenuate sepsis, indicating viability is required for the effect.
• The two strains differed in their in vitro SCFA production profiles.

Metabolome analysis revealed distinct SCFA patterns in sepsis mice, with elevated acetate and 3-hydroxybutyrate in blood and diminished butyrate and propionate in feces compared to sham controls.

• Blood metabolome showed elevated levels of acetate and 3-hydroxybutyrate in sepsis mice.
• Fecal metabolome showed diminished butyrate and propionate levels in sepsis mice compared to sham controls.
• These findings suggest compartment-specific SCFA dysregulation during sepsis.
• Analysis was conducted using metabolome analysis methodology.

Both probiotic strains similarly attenuated sepsis-induced gut dysbiosis, normalizing Firmicutes levels and reducing Proteobacteria.

• Fecal microbiome analysis was used to assess gut dysbiosis.
• Both fa1 and fg2 resulted in normalized Firmicutes levels.
• Both strains reduced Proteobacteria abundance in sepsis mice.
• Both probiotics produced similar levels of fecal SCFAs despite their different in vitro SCFA production profiles.

Butyrate, but not acetate, partly attenuated sepsis severity as measured by gut permeability and serum TNF-α.

• Butyrate administration resulted in partial attenuation of sepsis severity.
• Acetate administration did not attenuate sepsis severity.
• Outcome measures included gut permeability and serum TNF-α levels.
• This finding suggests differential roles for individual SCFAs in sepsis modulation.

Conditioned media from both probiotic strains and butyrate demonstrated protective effects against enterocyte injury induced by Klebsiella pneumoniae lysate, irrespective of SCFA production.

• Conditioned media from both fa1 and fg2 strains were protective against enterocyte injury.
• Butyrate also demonstrated protective effects against enterocyte injury.
• The protective effect was observed following activation by Klebsiella pneumoniae lysate.
• The protective effect was observed irrespective of the strains' SCFA production levels, suggesting additional mechanisms beyond SCFAs.

Patients with sepsis had lower serum SCFA levels compared to healthy controls.

• Serum SCFAs were measured in patients with sepsis and compared to healthy controls.
• Sepsis patients demonstrated lower serum SCFA levels than healthy controls.
• This clinical finding supports the potential use of SCFAs as biomarkers for sepsis disease monitoring.
• The finding translates the mouse model observations to a human clinical context.

L. rhamnosus strains fa1 and fg2 differed in their in vitro SCFA production profiles.

• The two strains were characterized for SCFA production in vitro prior to animal experiments.
• Despite different in vitro SCFA production, both strains produced similar levels of fecal SCFAs in the mouse model.
• This discordance between in vitro and in vivo SCFA production suggests the gut environment modulates probiotic SCFA output.