journal articles
FECAL MICROBIOTA TRANSPLANTATION MODULATES GUT MICROBIOME COMPOSITION AND GLIAL SIGNALING IN BRAIN AND COLON OF RATS WITH NEUROPATHIC PAIN: EVIDENCE FOR MICROBIOTA-GUT-BRAIN AXIS
C.-L. Shen, H. Deshmukh, J.M. Santos, M.M. Elmassry, P. Presto, Z. Driver, V. Bhakta, V. Yakhnitsa, T. Kiritoshi, G. Ji, J. Lovett, A. Hamood, V. Neugebauer
Despite evidence linking the gut microbiome to neuropathic pain (NP), it is not known if altering gut microbiota can alleviate NP via the microbiome-gut-brain axis. This study examined if healthy gut microbiota of sham male rats (Sham+V) and dysbiotic gut microbiota of NP rats (spinal nerve ligation: NP, SNL+V) can be disrupted and restored, respectively, via fecal microbiota transplant (FMT) from the opposite group [Sham+(SNL-FMT) and SNL+(Sham-FMT), respectively]. All groups received FMT daily for two weeks, followed by three weeks without FMT. SNL rats showed higher mechanical hypersensitivity [SNL+V vs. Sham+V] throughout the study. After two weeks, the FMT of healthy gut microbiota decreased mechanical hypersensitivity in SNL rats [SNL+(Sham-FMT) vs. SNL+V]. A temporal shift in microbiome profiles after 2-week FMT treatment was observed in Sham+(SNL-FMT) and SNL+(Sham-FMT) groups, while the microbiome profile shifted back a certain extent after FMT ceased. At the end of study, the Sham+(SNL-FMT) group acquired low abundance of UCG-001, Odoribacter, and Peptococcaceae, and high abundance of UBA1819 and Victivallis. The SNL+(Sham-FMT) group maintained high abundance of Butyricimonas and Escherichia-Shigella. The SNL+(Sham-FMT) group had altered glial and macrophage activation/inflammation markers in the brain/colon than the SNL+V group. Relative to the SNL+V group, the SNL+(Sham-FMT) group had significantly lower gene expressions of GFAP (hypothalamus), IBA-1 (colon), and NF-κB (amygdala/colon), but higher gene expressions of complex I (amygdala/hypothalamus) and claudin-3 (amygdala/hypothalamus/colon). In conclusion, FMT containing healthy microbiota given to SNL rats attenuates mechanical hypersensitivity, modulates microbiota composition, and mitigates downstream glial activation/inflammation markers in a NP model.
CITATION:
C.-L. Shen ; H. Deshmukh ; J.M. Santos ; M.M. Elmassry ; P. Presto ; Z. Driver ; V. Bhakta ; V. Yakhnitsa ; T. Kiritoshi ; G. Ji ; J. Lovett ; A. Hamood ; V. Neugebauer (2024): Fecal Microbiota Transplantation Modulates Gut Microbiome Composition and Glial Signaling in Brain and Colon of Rats with Neuropathic Pain: Evidence for Microbiota-Gut-Brain Axis. The Journal of Frailty and Aging (JFA). http://dx.doi.org/10.14283/jfa.2024.65