A
carefully reasoned and systematic approach is needed to
pick
the next best targets and develop disease-specific protocols.
Undoubtedly,
repair of microbial community structure following an
ecological
catastrophe is likely to be an easier target. One such nonCDI
example occurs in the setting of bone marrow transplantation
(BMT),
where patients are subjected to intensive rounds of body
irradiation,
chemotherapy, and broad-spectrum antibiotics during
their
pre-BMT conditioning period, all of which are known to dis-
rupt
gut microbiota and microbial-host homeostasis [41]. Loss of
microbial
diversity in fecal microbiota of these patients is comparable
to that seen in patients with RCDI. In many patients groups such
as
the Enterococci or -Proteobacteria, which are more adept at
gut
translocation than most commensal organisms, become dominant
over all other bacterial constituents of gut microbiota [41].
Such
overgrowth is associated with systemic bacteremia that is
commonly
observed after BMT. It is reasonable to hypothesize
that
well-timed FMT in these patients resulting in normalization
of
their gut microbial communities may prevent these common
infectious
complications. In fact, FMT in a murine model can clear
antibiotic-associated
colonization by vancomycin-resistant Enterococcus,
although potency of FMT is dependent on densities of key
microbial
taxa in the donor preparation [42]. It is also possible that
host-microbe
interactions that can enhance development of regulatory
immune circuits following BMT, e.g., regulatory T cell inducing
taxa of Clostridia [43], will have an important benefit of dampening
pathological
graft versus host responses that complicate long-term
outcomes
in these patients.
Interestingly,
the idea of microbiota therapy, or “reconventionalization”,
of antibiotic-treated immunosuppressed or
immunodeficient
patients dates back many decades. It was recognized
then that gut anaerobes provide colonization resistance,
and
a handful of patients with congenital immune deficiency or
undergoing
bone marrow transplantation were treated with fecal
suspensions
or microbiota propagated in germ-free mice [44,45].
Development
did not go beyond clinical anecdotes and management
of infectious complications in these challenging situations
since
has relied on increasingly broad-spectrum antibiotics.