And the winners are: MS MICROBIAL CANDIDATES

​Here’s what I know—and it isn’t as much as it should be but it is something, which is better than nothing: Oligoclonal bands (OCBs) are the key to the cause of MS. They can be unlocked to reveal their secrets. We believe now, based on the MS brain sequencing work, that these bands of healing marauders are directed mostly against anaerobic bacteria. 
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That’s where the Microbes in MS research team is diving into deep, uncharted waters.

We’ve seen that RNA sequences within MS brain lesions differ significantly from their epilepsy control counterparts as reported in Scientific Reports. Twenty-nine MS candidate microbes were identified. We know that the MS lesions we studied contain more bacterial sequences; they’re “dirtier” than the controls. Further, most of these MS candidate microbes happen to be anaerobic bacteria. That is, MS seems to be related to (fussy!) bacteria that live primarily in areas lacking oxygen. Emily Eckman is busy working in our laboratory to grow and validate some of these microbes so that we can develop tests against them.
 
Anaerobic bacteria, found commonly in the gut, mouth, skin and vagina, generally go about their business as a normal part of the microbial world. But they sometimes cause infections. These anaerobic infections can be both indolent (progressing slowly) and polymicrobial (having multiple infectious agents), which makes detecting them complex. That’s the power and beauty of deep sequencing: It can reveal multiple bacteria in a lesion and show us the anaerobic bacteria that don’t grow well in lab cultures—the so-called “unculturables” or “uncultivatables.” Some of these microbes are found only in mixtures with their friends, who supply some of the necessary nutrients.
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Here is the MS Microbial Candidate List derived from the Microbes in MS team’s
​deep sequencing data:

Which of these MS microbial candidates do we believe might actually be contributing to the disease? It’s hard to know a priori, but some candidates are more attractive (if bacteria can actually be “attractive”) than others. For instance, #2 on the list, Atopobium, is found mainly in the vagina. If we can confirm this finding in further research, the presence of Atopobium could help explain the female predominance of MS. Since men don’t have vaginas, they could not get at least some strains of Atopobium, and they don’t have MS nearly as often. However, Atopobium has been described as a contaminant in other sequencing studies, so it may or may not be a real finding. Another “attractive” MS candidate is Akkermansia, because it was shown by another group in another study to be more abundant in the stool of MS patients compared with controls. We found this anaerobic human gut bacterium in brain samples, not stool samples, but the parallel is interesting. We did not find Akkermansia in the controls, at all. Likewise, the most abundant MS candidate microbe, Nitrosospira, also was not found in the control specimens. Neither Akkermansia nor Nitrosospira are believed to be common contaminants, and the best defense against contamination is to run controls—which we did. 

How can we know what microbes may be causal for MS, and which may be spurious? There is a way. Stay tuned for the next blog topic: Macrophages and Immunohistochemistry. It may not sound like riveting stuff, but I’d start popping the popcorn now.

​Shutterstock bacteria illustration ID: 734835721