Gut dysbiosis impairs recovery after spinal cord injury.
The trillions of microbes that exist in the gastrointestinal tract have emerged as pivotal regulators of mammalian development and physiology. Disruption of this gut microbiome, a process known as dysbiosis, causes or exacerbates various diseases, but whether gut dysbiosis affects recovery of neurological function or lesion pathology after traumatic spinal cord injury (SCI) is unknown. Data in this study show that SCI increases intestinal permeability and bacterial translocation from the gut. These changes are associated with immune cell activation in gut-associated lymphoid tissues (GALTs) and significant changes in the composition of both major and minor gut bacterial taxa. Postinjury changes in gut microbiota persist for at least one month and predict the magnitude of locomotor impairment. Experimental induction of gut dysbiosis in naive mice before SCI (e.g., via oral delivery of broad-spectrum antibiotics) exacerbates neurological impairment and spinal cord pathology after SCI. Conversely, feeding SCI mice commercial probiotics (VSL#3) enriched with lactic acid-producing bacteria triggers a protective immune response in GALTs and confers neuroprotection with improved locomotor recovery. Our data reveal a previously unknown role for the gut microbiota in influencing recovery of neurological function and neuropathology after SCI.
Department of Neuroscience, Center for Brain and Spinal Cord Repair, Wexner Medical Center, The Ohio State University, Columbus, OH 43210.
Kristina A
0000-0002-1652-0882
KA
Kigerl
Department of Neuroscience, Center for Brain and Spinal Cord Repair, Wexner Medical Center, The Ohio State University, Columbus, OH 43210.
Jodie C E
0000-0002-4820-6070
JC
Hall
Department of Animal Sciences, The Ohio State University, Columbus, OH 43210.
Lingling
L
Wang
Center for Biostatistics, The Ohio State University, Columbus, OH 43210.
Xiaokui
X
Mo
Department of Animal Sciences, The Ohio State University, Columbus, OH 43210.
Zhongtang
0000-0002-6165-8522
Z
Yu
Department of Neuroscience, Center for Brain and Spinal Cord Repair, Wexner Medical Center, The Ohio State University, Columbus, OH 43210 Phillip.Popovich@osumc.edu.
Phillip G
PG
Popovich
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D018988:Bacterial Translocation / Q000187:drug effects; D064806:Dysbiosis / Q000150:complications* / Q000188:drug therapy / Q000473:pathology*; D000069196:Gastrointestinal Microbiome / Q000187:drug effects; D041981:Gastrointestinal Tract / Q000382:microbiology*; D007109:Immunity / Q000187:drug effects; D007249:Inflammation / Q000150:complications / Q000473:pathology; D008221:Lymphoid Tissue / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D000066829:Neuroprotection / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D010641:Phenotype; D019936:Probiotics / Q000494:pharmacology / Q000627:therapeutic use; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D020127:Recovery of Function / Q000187:drug effects; D017423:Sequence Analysis, RNA; D013119:Spinal Cord Injuries / Q000150:complications* / Q000188:drug therapy / Q000382:microbiology / Q000503:physiopathology*
D000900:Anti-Bacterial Agents; D012336:RNA, Ribosomal, 16S