A pilot project to define microbiota bottlenecks using the trajectory of subspecies clade allele frequencies through high-definition personalized analysis in individual Crohn’s disease patients and controls

Principal investigator:
Prof. Dr. med. Andrew J. Macpherson, Department of Visceral Surgery and Medicine, Inselspital. For more information, visit the website

 

Humans live in association with enormous numbers of microbes in the lower intestine and on other body
surfaces. Beneficial host-microbial complementation of metabolism, immune stimulation and host
epigenetics can be compromised if these microbial taxa present fail in these functions, or actively damage
the host. We have recently published data showing the clusters of microbes associated with a severe longterm
course of Crohn’s disease independently of disease activity. Through sequencing single bacterial
genomes in animal models, we have demonstrated different clades with emblematic genomic variants
within a single bacterial species whose proportions remain relatively stable over a timescale of years. We
hypothesize that the stable allele frequency of clade representation will be disrupted if microbiota
bottlenecks occur, such as in active Crohn’s disease. In this one-year pilot study to operationalize the Bern
personalized medicine unit, we will leverage this experience and our patient cohorts to test whether the
trajectory of clade representation within single dominant microbiota species in individual Crohn’s
disease patients or healthy controls can be used to determine the occurrence of microbiota
bottlenecks. This approach has the potential advantage that each species within an individual patient
is used as its own control. In addition to building capacity in Bern for studies of host-microbial mutualism,
the intended impact is to identify the potential openings for beneficial microbiota manipulation at
critical phases of Crohn’s disease.