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Cell-Free Supernatant of Lactobacillus rhamnosus and Bifidobacterium breve Ameliorates Ischemic Stroke-Generated Neurological Deficits in Rats

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Abstract

The beneficial effects of probiotics, postbiotics, and paraprobiotics have already been registered in managing ischemic stroke-generated neuroinflammation and gut dysbiosis. Herein, we examined the impact of cell-free supernatant (CFS) obtained from probiotics (Lactobacillus rhamnosus UBLR-58 and Bifidobacterium breve UBBr-01) in a rat transient middle cerebral artery occlusion (MCAO) model of focal cerebral injury. Pre-MCAO supplementation of probiotics (2 × 109 CFU/mL) for 21 days or CFS (1 mL/rat) for 7 days protect the MCAO-induced somatosensory and motor impairments recorded at 24 h and 72 h after reperfusion in foot-fault, rotarod, adhesive removal, and vibrissae-evoked forelimb placing tests. We also noted the reduced infarct area and neuronal degradation in the right hemisphere of probiotics- and CFS-recipient MCAO-operated animals. Moreover, MCAO-induced altered concentrations of glial-fibrillary acidic protein, NeuN, zonula occludens-1 (ZO-1), TLR4, IL-1β, IL-6, and TNF-α, as well as matrix metalloproteinase-9 (MMP9) were reversed in the treatment groups. Probiotics and CFS treatment ameliorated the elevated levels of IL-6, IL-1β, and MMP9 in the blood plasma of rats. The disrupted microbial phyla, Firmicutes-to-Bacteroides ratio, villi/crypt ratio, and decreased mucin-producing goblet cells, ZO-1, and occludin in the colon of MCAO-operated rats were recovered following probiotics and CFS treatment. NMR characterization of CFS and rat blood plasma revealed the presence of several important bacterial metabolites. These findings suggest that the CFS obtained from Lactobacillus rhamnosus UBLR-58 and Bifidobacterium breve UBBr-01 has the propensity to improve MCAO-generated neurological dysfunctions in rats by dampening neuroinflammation and modulating the gut-brain axis modulators.

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Acknowledgements

The Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, and Government of India are acknowledged for their financial support by the authors (ZR, HPP, and MPD). The authors also want to thank Unique Biotech Limited, Hyderabad, India, for providing Lactobacillus rhamnosus UBLR-58 and Bifidobacterium breve UBBr-01 and CFS as gift samples.

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Authors and Affiliations

  1. Department of Biological Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, PIN 500037, Telangana, India

    Ziaur Rahman & Manoj P. Dandekar

  2. Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana, India

    Hara Prasad Padhy

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  2. Hara Prasad Padhy
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  3. Manoj P. Dandekar
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Contributions

ZR carried out the research, compiled the findings, and wrote the article; HPP carried out NMR, and this article was conceptualized, evaluated, and improved by MPD.

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Correspondence to Manoj P. Dandekar.

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Rahman, Z., Padhy, H.P. & Dandekar, M.P. Cell-Free Supernatant of Lactobacillus rhamnosus and Bifidobacterium breve Ameliorates Ischemic Stroke-Generated Neurological Deficits in Rats. Probiotics & Antimicro. Prot. (2024). https://doi.org/10.1007/s12602-024-10256-w

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