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AI InsightThe inability to sustain cellular homeostasis under stress likely triggers myocytic injury, highlighting the potential for targeted metabolic resuscitation in dysbiotic trauma populations.
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Özet
Background: Hemorrhagic shock is characterized by rapid bioenergetic failure and cellular collapse, remains a primary driver of trauma-related mortality. While the gut microbiome is established as a systemic metabolic regulator, its contribution to physiological reserve during acute traumatic insult remains to be fully elucidated. We hypothesized that maternal antibiotic-induced dysbiosis programs a metabolically vulnerable phenotype in offspring, potentially compromising the compensatory response to severe hemorrhage. Methods: A vertical transmission model of dysbiosis was established using Sprague Dawley rats. Pregnant dams received broad-spectrum antibiotics (Vancomycin and Amoxicillin) during late gestation and lactation. Male offspring (n=7/group) continued the regimen until 8 weeks of age, followed by a 4-week washout period. Controls received vehicle. At 12 weeks, a volume-controlled hemorrhagic shock (1.5 mL/100g body weight) was induced. Systemic metabolic profiles (glucose, lipids), tissue injury markers (Creatine Kinase (CK), Amylase), and intestinal morphometrics were evaluated. Results: Control animals demonstrated a typical adaptive stress hyperglycemic response following hemorrhage. In contrast, dysbiotic offspring exhibited significant refractory hypoglycemia (p < 0.001) and failed to mobilize glucose reserves, suggesting an impairment in acute energy mobilization. Despite this systemic energy deficit, dysbiotic rats maintained persistent hypercholesterolemia. Notably, the dysbiotic group developed severe muscle injury, indicated by an approximately two-fold elevation in serum CK levels (p < 0.01) compared to controls. This occurred without concomitant elevations in serum amylase or significant changes in intestinal weight, suggesting that the observed rhabdomyolysis may stem from specific bioenergetic failure rather than generalized organ atrophy. Conclusion: Maternal dysbiosis appears to program a state of metabolic insufficiency in offspring, characterized by a failure in adaptive hyperglycemia and an increased susceptibility to metabolic rhabdomyolysis during shock. These findings suggest that the gut microbiome may be an independent determinant of trauma tolerance. The inability to sustain cellular homeostasis under stress likely triggers myocytic injury, highlighting the potential for targeted metabolic resuscitation in dysbiotic trauma populations.
Abstract
Background: Hemorrhagic shock is characterized by rapid bioenergetic failure and cellular collapse, remains a primary driver of trauma-related mortality. While the gut microbiome is established as a systemic metabolic regulator, its contribution to physiological reserve during acute traumatic insult remains to be fully elucidated. We hypothesized that maternal antibiotic-induced dysbiosis programs a metabolically vulnerable phenotype in offspring, potentially compromising the compensatory response to severe hemorrhage. Methods: A vertical transmission model of dysbiosis was established using Sprague Dawley rats. Pregnant dams received broad-spectrum antibiotics (Vancomycin and Amoxicillin) during late gestation and lactation. Male offspring (n=7/group) continued the regimen until 8 weeks of age, followed by a 4-week washout period. Controls received vehicle. At 12 weeks, a volume-controlled hemorrhagic shock (1.5 mL/100g body weight) was induced. Systemic metabolic profiles (glucose, lipids), tissue injury markers (Creatine Kinase (CK), Amylase), and intestinal morphometrics were evaluated. Results: Control animals demonstrated a typical adaptive stress hyperglycemic response following hemorrhage. In contrast, dysbiotic offspring exhibited significant refractory hypoglycemia (p < 0.001) and failed to mobilize glucose reserves, suggesting an impairment in acute energy mobilization. Despite this systemic energy deficit, dysbiotic rats maintained persistent hypercholesterolemia. Notably, the dysbiotic group developed severe muscle injury, indicated by an approximately two-fold elevation in serum CK levels (p < 0.01) compared to controls. This occurred without concomitant elevations in serum amylase or significant changes in intestinal weight, suggesting that the observed rhabdomyolysis may stem from specific bioenergetic failure rather than generalized organ atrophy. Conclusion: Maternal dysbiosis appears to program a state of metabolic insufficiency in offspring, characterized by a failure in adaptive hyperglycemia and an increased susceptibility to metabolic rhabdomyolysis during shock. These findings suggest that the gut microbiome may be an independent determinant of trauma tolerance. The inability to sustain cellular homeostasis under stress likely triggers myocytic injury, highlighting the potential for targeted metabolic resuscitation in dysbiotic trauma populations.