Lactobacillus reuteri attenuates cardiac injury without lowering cholesterol in low-density lipoprotein receptor-deficient mice fed standard chow

摘要

Koppinger MP, Lopez-Pier MA, Skaria R, Harris PR, Konhilas JP. Lactobacillus reuteri attenuates cardiac injury without lowering cholesterol in low-density lipoprotein receptor-deficient mice fed standard chow. Am J Physiol Heart Circ Physiol 319: H32-H41, 2020. First published May 15, 2020; doi:10.1152/ajpheart.00569. 2019.—Disruption of the normal gut microbiome (dysbiosis) is implicated in the progression and severity of myriad disorders, including hypercholesterolemia and cardiovascular disease. Probiotics attenuate and reverse gut dysbiosis to improve cardiovascular risk factors like hypertension and hypercholesterolemia. Lactobacillus reuteri is a well-studied lactic acid-producing probiotic with known cholesterol-lowering properties and anti-inflammatory effects. In the present study, we hypothesized that L reuteri delivered to hypercholester-olemic low-density lipoprotein receptor knockout (LDLr KO) mice will reduce cholesterol levels and minimize cardiac injury from an ischemic insult. L. reuteri [1 × 10~9 or 50 × 10~6 colony-forming units (CFU)/day] was administered by oral gavage to wild-type mice and LDLr KO for up to 6 wk followed by an ischemia-reperfusion (I/R) protocol. After 4 wk of gavage, total serum cholesterol in wild-type mice receiving saline was 113.5 ±5.6 mg/dL compared with 113.3 ± 6.8 and 101.9 ± 7.5 mg/dL in mice receiving 1 × 10~9 or 50 × 10~6 CFU/day, respectively. Over the same time frame, administration of L. reuteri at 1 × 10~9 or 50 × 10~6 CFU/day did not lower total serum cholesterol (283.0 ± 11.1, 263.3 ± 5.0, and 253.1 ± 7.0 mg/dL; saline, 1 × 10~9 or 50 × 10~6 CFU/day, respectively) in LDLr KO mice. Despite no impact on total serum cholesterol, L. reuteri administration significantly attenuated cardiac injury following I/R, as evidenced by smaller infarct sizes compared with controls in both wild-type and LDLr KO groups. In conclusion, daily L. reuteri significantly protected against cardiac injury without lowering cholesterol levels, suggesting anti-inflammatory properties of L. reuteri uncoupled from improvements in serum cholesterol. NEW & NOTEWORTHY We demonstrated that daily delivery of Lactobacillus reuteri to wild-type and hypercholesterolemic lipoprotein receptor knockout mice attenuated cardiac injury following ischemia-reperfusion without lowering total serum cholesterol in the short term. In addition, we validated protection against cardiac injury using histology and immunohistochemistry techniques. L. reuteri offers promise as a probiotic to mitigate ischemic cardiac injury.