Monday, December 15, 2014

Commensal virus to the rescue

We all heard about gut microbiome and how an important job they do to keep us healthy. Still, there is the situations when the antibiotic therapy is necessary. 

Since many beneficial microbes in our gut are sensitive to broad spectrum antibiotics used in today's medicine, such treatment could lead to dysbacteriosis and gut inflammation. Now, beneficial microbiome therapy (fecal transplantation) is an obvious option, but such therapy could be inefficient due to the fact that such flora itself is sensitive to antibiotics. So what is the solution?

It appears that some friendly viruses in the gut could provide such beneficial, cover effect. Such study, led by Ken Cadwell from New York University School of Medicine, was recently published in journal Nature.

The authors studied the murine norovirus (MNV). This virus is endemic in laboratory mice colonies but does not produce an overt gut inflammation in a immune-competent host. 

Reconstitution of germ-free mice with MNV produced changes in the gut morphology and immune cells resembling conventional mice gut

More relevant, MNV could reverse antibiotic-induced negative effects on gut immune system.

Mechanistically, such beneficial effect of MNV on gut immune system was type I IFN dependent.
Finally, MNV could prevent antibiotic-induced gut sensitivity to chemical damage (DSS).

In summary, the authors showed that viral therapy could be an viable alternative (since virus would not be sensitive to antibiotic itself) to treat or prevent antibiotic-induced gut immune malfunctions.

Of course, application of this study to human population would require additional research. 

First, human Norovirus is clearly not a benign virus (cruise ship virus). So we need to find the virus that does not induce an overt gut inflammation in healthy humans. 

Second, this study examined immune-competent mice. However, analyses of immune-deficient mice responses to NMV would be more informative since in humans, antibiotic therapies are frequently used to compensate for immune deficiencies.

Third, if gut commensal, beneficial viruses exist, they should naturally (automatically) take over the beneficial microbes functions during antibiotic treatment. Do they do it?

Fourth, recent studies indicated that viruses, including MNV, require the presence of bacteria for their infectivity. How this knowledge affects the results of this study is to be determined.

David Usharauli

1 comment:

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