Saturday, December 9, 2017

From microbiome-association studies to causal microbe identification

As new Nature study says "the general inability to move beyond correlations and address causation has been the Achilles heel of microbiome research." Well said. Indeed, notwithstanding of so many microbiome studies, the number of identified microbiota species specifically and reproducibly linked to a particular [medical] condition is still zero.  

Is there a way to overcome this challenge? Maybe one could compare microbiome content of the hosts displaying variable clinical phenotype [DSS colitis, in this case] and find one microbial species, if you are lucky, that control that phenotype in every host? But isn't this approach exactly what all other studies have done all along? 

And actually, how strong is the data in support of this approach? The authors showed that germ-free mice and germ-free mice colonized with mouse microbiota derived from SPF mice (MMb mice) were highly sensitive to DSS colitis induction compared to SPF mice or germ-free mice colonized with human microbiota (HMb mice). Of note, observed difference in survival between MMb and SPF is strange since both should have SPF microbiota.

When the authors compared several pairs of mice strains housed separately or co-housed, they found that sensitivity to DSS colitis segregated with presence of Lachnospiraceae species (Clostridium immunis).       

Indeed, colonization of germ-free mice with human microbiota enriched with Clostridium immunis could improve mice survival in DSS colitis model.

However, again, survival data between different mouse strains did not correlate with level of Lachnospiraceae species, questioning simplicity of one-on-one relationship between Clostridium immunis and colitis score (HMb and SPF have similar survival curve but vastly differ in Lachnospiraceae content).

In summary, without more data and confirmation by other labs I will view these data as very preliminary and unverified with lots of caveats. Surely, not a Nature material in my opinion.

posted by David Usharauli

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