Laboratory Animals - June Issue - 255

Viney
investigated in wild animals, and here I suggest how
addressing these questions in wild, rather than laboratory, animals may greatly facilitate microbiota research.

Host-microbiota immunological interface
Work with laboratory animals has shown that the gut
microbiota stimulates a host immune response, notably
the generation of secretory immunoglobulin A (sIgA)
antibodies by the gut mucosa.28 This response corrals
the microbiota to the gut and can also alter its composition.29 However, the mechanisms by which sIgA and
other components of the immune response aﬀect the
gut bacteria is far from fully elucidated.30
The gut microbiota is a mixture of many diﬀerent
bacterial taxa. Many, if not most, of these taxa are
commensal; a small number are pathogens. But,
beyond this simple dichotomy, whether or not a bacterial taxon is pathogenic also depends upon its context - which other bacterial taxa it occurs with, but also
the physiological and immunological state of the host.
The host sIgA response diﬀers for diﬀerent bacterial
taxa, shown by some microbiota bacteria having IgA
on their surface, but others not.31 IgA-negative gut bacteria are, presumably, commensal, but many of the
IgA-positive taxa are presumably commensal too,
though among this fraction some will also be pathogens, or potential pathogens. Discordance between
the microbiota of wild and laboratory animals (and
fewer potential pathogens in laboratory animals) suggest that unpicking the complex interplay between commensal and pathogenic taxa is most appropriately
studied in wild animals.
Also of relevance here is work that has studied the
immune responses of wild animals, ﬁnding that they
diﬀer quantitatively in their immune responses compared
with laboratory animals, having elevated humoral and
cellular responses, but depressed cytokine responses.4
These immunological diﬀerences are likely to be due to
wild animals being exposed to more infections in the wild
resulting in stimulation of the immune system, with down
regulation of some immune components being required
to avoid inducing immunopathology.3,32
How the gut immune response shapes the gut
microbiota community, and how the gut microbiota
itself modiﬁes the gut immune response, is not yet
well understood. Given the extensive inter-individual
heterogeneity in gut microbiota composition in wild
animals, this raises the questions of (a) whether this
is caused by immunoheterogeneity among wild animals,
for example due to diﬀerent exposure to other infectious agents, and/or (b) whether diﬀerent gut microbiota have systemic immunological eﬀects that aﬀects
animals' susceptibility or resistance to other infectious
agents?

255
More broadly still, beyond bacteria and viruses,
the gut of wild animals is also home to protozoan
and helminth parasites, each of which will likely aﬀect
the bacterial microbiota, both directly and indirectly.
Indeed, it has been shown that one nematode parasite,
Trichuris muris, requires a bacterial microbiota for
the hatching of its eggs and to facilitate parasite establishment in a host,33,34 showcasing the potential complex, multi-trophic interactions occurring within a gut
ecosystem.
While in laboratory animals there has been detailed
study of the immunology of infections of single parasite
species (and sometimes multiple species), the rich, complex gut community present in wild animals is unlikely
to be usefully replicated in laboratory animals. It seems
inevitable that these multiple parasite species in the
gut will have far-reaching eﬀects on the gut bacterial
microbiota, emphasising that these phenomena need to
be studied in naturally infected animal populations
to comprehensively understand the gut microbiota.
The diﬀerent infections that individual wild animals
will have is potentially a challenge when seeking to
unpick the relative eﬀects of these other infections
and of the microbiota on animals. It is important therefore, that such studies will need to be suﬃciently robust
to be able to account for these potential multifactorial
eﬀects.

Drivers of microbiota community
composition
Understanding how the microbiota community is constructed and maintained is a major theme in microbiota
research, in part overlapping with immunological considerations (above). Studies in laboratory animals have
shown that the abundance of components of the microbiota can be heritable - a measure of the proportion of
the phenotypic variance of the trait in question that can
be explained genetically.35,36 There is considerable
interest in understanding the mechanistic basis of
such heritability.
That there is signiﬁcant inter-individual heterogeneity in wild rodents' gut microbiota suggests that wild
animals have more microbiota phenotypic variation
to be explained, compared with laboratory animals.
This may have the consequence that the actual heritability of these microbiota traits will be lower in
wild animals, compared with estimates derived from
studies of laboratory animals. This therefore suggests
that to properly quantify the heritability of aspects of
the gut microbiota requires that this is studied in wild
animals.
The lives of wild animals also vary in time and
space. Of particular note, wild animals' diet varies particularly seasonally which (as discussed above) can
Laboratory Animals - June Issue

Table of Contents for the Digital Edition of Laboratory Animals - June Issue
