Metagenomic analyzes used to identify changes in the gut microbiome after spinal cord injury


Washington, DC – May 11, 2021 – Using metagenomic sequencing, researchers have identified changes in populations of bacteria and viruses that occur after spinal cord injury in mice. The new metagenomic datasets, presented in mSystems, an open access journal of the American Society for Microbiology, provides new information on the taxonomy and function of various microbes, including viruses. This information may help better predict how changes induced by spinal cord injury in the microbiome influence systemic and neurological outcomes after traumatic spinal cord injury.

“This is the first study that has applied metagenomics to characterize intestinal dysbiosis after spinal cord injury,” said study principal investigator Phillip Popovich, PhD, professor and head of the department of neuroscience and executive director of the Belford Center for Spinal Ohio State University (OSU). “Many people are interested in understanding the gut microbiome because of its potential impact on a multitude of co-morbidities that affect people with spinal cord injury, including metabolic disease, cardiovascular dysfunction, impaired immune function, fatigue and mental health issues. a lot of literature in other areas that involve the gut microbiome in the onset or progression of these comorbidities. ”

“We were able to show spinal cord injury-dependent effects on a number of different bacteria and viruses – some are increasing, some are decreasing, and some are virtually exhausted from the injury,” said Matthew Sullivan, PhD, Professor, Department of Microbiology and Founding Director of OSU’s Center for Microbiome Science and co-lead author of the study. “And because we used advanced genome-resolved metagenomics and viromics, we were able to do more than determine how spinal cord injury affects the number and composition of gut bacteria. By comparison, metagenomic sequencing allows us to simultaneously assess how spinal cord injury affects bacteria, archaea, fungi, and viruses, and then begin to predict the functional consequences associated with these changes in the microbial ecosystem of intestine. ”

The application of metagenomics to study the microbiome of mammals is still a relatively new approach, but these techniques have long been used to understand microbial diversity in the oceans. In fact, Dr. Sullivan used these techniques to determine the impact of viruses found in the ocean on global biogeochemistry.

In the new study, the researchers performed spinal cord injuries on the 4th thoracic spine (T4) or 10th thoracic spine (T10) in mice, then compared their results to mice with sham injuries (i.e. (i.e. spine surgeries without spinal cord injury). They collected fecal samples at baseline and three weeks after the injury (or surgery), then performed metagenomic analyzes. Researchers found that after spinal cord injury, the relative abundance of several beneficial bacteria decreased, while potentially pathogenic bacteria increased. They also found that functionally, microbial genes encoding proteins for the biosynthesis of tryptophan, vitamin B6, and folate, pathways essential for central nervous system function, were reduced after spinal cord injury. Viruses from beneficial bacterial hosts decreased, while viruses from pathogenic bacterial hosts increased after spinal cord injury.

“Spinal cord injury occurs at different levels of the spinal cord, and the level at which injury occurs will have distinct effects on the gut and the microbiome,” said Dr. Popovich. Indeed, the researchers found that although the microbiomes and viromes were altered in all mice with spinal cord injury, some of these changes were noticeably improved in mice with spinal cord injuries higher up. level.

Although this is a pilot study and not yet in humans, the results provide the first steps for the development of therapies and treatments. For example, Lactobacillus johnsonii, which decreased in mice after spinal cord injury, was a primary source of lactocepin which is an anti-inflammatory bacterial protease essential for proper immune function. Thus, replacing Lactobacillus johnsonii with bespoke probiotics could help boost immune responses and reverse infectious complications that plague people with spinal cord injuries.

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