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Lactobacillus Helveticus Improves Controlled Cortical Impact Injury-Generated Neurological Aberrations by Remodeling of Gut-Brain Axis Mediators

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Considerable studies augured the potential of gut microbiota-based interventions in brain injury-associated complications. Based on our earlier study results, we envisaged the sex-specific neuroprotective effect of Lactobacillus helveticus by remodeling of gut-brain axis. In this study, we investigated the effect of L. helveticus on neurological complications in a mouse model of controlled cortical impact (CCI). Adult, male and female, C57BL/6 mice underwent CCI surgery and received L. helveticus treatment for six weeks. Sensorimotor function was evaluated via neurological severity score and rotarod test. Long-term effects on anxiety-like behavior and cognition were assessed using the elevated-zero maze (EZM) and novel object recognition test (NORT). Brain perilesional area, blood, colon, and fecal samples were collected post-CCI for molecular biology analysis. CCI-operated mice displayed significant neurological impairments at 1-, 3-, 5-, and 7-days post-injury (dpi) and exhibited altered behavior in EZM and NORT compared to sham-operated mice. However, these behavioral changes were ameliorated in mice receiving L. helveticus. GFAP, Iba-1, TNF-α, and IL-1β expressions and corticotrophin-releasing hormone (CRH) levels were elevated in the perilesional cortex of CCI-operated male/female mice. These elevated biomarkers and decreased BDNF levels in both male/female mice were modified by L. helveticus treatment. Additionally, L. helveticus treatment restored altered short-chain fatty acids (SCFAs) levels in fecal samples and improved intestinal integrity but did not affect decreased plasma levels of progesterone and testosterone in CCI mice. These results indicate that L. helveticus exerts beneficial effects in the CCI mouse model by mitigating inflammation and remodeling of gut microbiota-brain mediators.

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Acknowledgements

The authors express their gratitude to NIPER, Hyderabad for providing the necessary resources.

Funding

This work is funded by the DST-SERB (SRG/2020/002439).

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India

    Tulasi Pasam & Manoj P. Dandekar

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

    Hara Prasad Padhy

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  2. Hara Prasad Padhy
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Contributions

TP conceptualized the study design and executed all the experiments, data analysis, and manuscript drafting. HP analyzed SCFAs using NMR, and MPD assisted in the conceptualization of the hypothesis, and supervised the study, and edited the manuscript. All authors read and approved the final manuscript.

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Correspondence to Manoj P. Dandekar.

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The animal studies were approved by the Institutional Animal Ethics Committee of the NIPER, Hyderabad (Approval number: NIP/10/2020/PC/377a). The studies were conducted in accordance with the local legislation and institutional requirements.

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Pasam, T., Padhy, H.P. & Dandekar, M.P. Lactobacillus Helveticus Improves Controlled Cortical Impact Injury-Generated Neurological Aberrations by Remodeling of Gut-Brain Axis Mediators. Neurochem Res 50, 3 (2025). https://doi.org/10.1007/s11064-024-04251-4

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