In the early, online edition of the Proceedings of the National Academy of Sciences, independent research teams explore potential ties between the gut microbiome and multiple sclerosis.
For the first of these, researchers from Germany, China, and the US began by comparing gut microbiome patterns in 34 identical twin pairs discordant for the disease, profiling gut microbe community members and gene repertoires with 16 ribosomal RNA sequencing and metagenomic sequencing. Microbes such as Akkermansia muciniphila appear somewhat over-represented in untreated twins with MS, though they found that the general gut microbiome profiles were comparable. Even so, the team's subsequent experiments suggest that gut microbes from the MS-affected twins corresponded with a boost in central nervous system inflammation and a dip in anti-inflammatory interleukin IL-10 production by immune cells in mouse models of brain autoimmunity.
A University of California, San Francisco-led team takes a look at potential gut microbe influences on immune activity in MS. Using 16S rRNA sequencing, the researchers considered gut microbe community membership in 71 individuals with MS and 71 without. They also exposed peripheral blood mononuclear cells (PBMC) from cases and controls to extracts from their own gut microbe samples. Results from that study support the notion that gut microbes can impact MS-related immune processes. MS-enhanced microbes such as A. muciniphila or Acinetobacter calcoaceticus led to pro-inflammatory features in the PBMC cells or mouse models, for example, while a species found at diminished levels in the MS gut microbiome appeared to kick off IL-10 activity. And again, autoimmunity was enhanced in germ-free mouse models that received microbes from the human MS patients.
Finally, investigators from Johns Hopkins University and elsewhere follow up on findings from a prior genome-wide association study pointing to ties between bipolar disorder and variants affecting the ankyrin-G-coding gene ANK3. With that in mind, the team established a mouse model that is missing most forms of ankyrin-G in forebrain pyramidal neuron under specific experimental conditions in the adult animals. Along with changes in neuronal activity in the mouse brain region, the authors note that the ANK3 knockout animals "showed robust behavioral phenotypes reminiscent of aspects of human mania, ameliorated by anti-mania drugs."