HSSs reveal reproducible and host-species specific humanization of
microbial genera in captive NHPs
Identifying differentially abundant ASVs and genera between matched wild
and captive populations can reveal the effects of captivity on specific
constituents of the NHP gut microbiota. However, these analyses alone do
not provide information about the extent to which specific microbial
clades within the captive NHP gut microbiota are humanized. Here, we
define humanization of a microbial clade in a captive NHP population as
the replacement of endogenous ASVs in the clade (i.e., ASVs found in
wild NHP populations) by ASVs found in humans or the parallel absence
from captive NHP populations and humans of ASVs in the clade found in
wild conspecific NHP populations.
To assess the degree of humanization for each gut microbial clade in
each captive NHP population, we tested whether the ASV-compositions of
individual microbial genera in captive NHPs were more similar to those
of the genera in humans (i.e., humanized) or to those of the genera in
wild living conspecific individuals. These analyses allowed us to
identify microbial genera in each captive NHP population whose
endogenous host-species specific ASVs (i.e., ASVs private to wild
conspecific hosts) displayed evidence of loss or of replacement by ASVs
found in humans. We developed a statistic, Host Specificity Score (HSSs)
(Materials and Methods), which can be calculated for any microbial clade
or taxonomic rank of arbitrary phylogenetic depth. Here, we calculated
these scores at the level of microbial genus, which was the finest-scale
taxonomic resolution allowed by the 16S rDNA amplicon sequences in our
dataset. Log-transformed HSSs are normally distributed around 0 and
provide a quantitative ranking of the degree of humanization for all
microbial genera in the gut microbiotas of a captive population, with
lower scores indicating a greater degree of humanization.
Log-transformed HSSs >0 indicate the ASV composition of the
genus is more similar between captive primates and wild-living
conspecifics than between captive primates and humans. Conversely,
log-transformed HSSs <0 indicate that the ASV composition of
the genus is more similar between captive primates and humans than
between captive primates and wild-living conspecifics. Humanization of
the ASV composition of a microbial genus in a captive NHP population, as
indicated by a negative HSS, could be underlain by the loss of ASVs
found in wild conspecific NHPs but not found in humans or the gain of
ASVs found in humans but not found in wild conspecific NHPs.
Calculating HSSs for each microbial genus for each captive NHP
population indicated that some genera in the captive NHP gut microbiota
were humanized, whereas others were retained from the wild. An example
of a bacterial genus that was humanized in captive chimpanzees in the
United States (i.e., the genus Collinsella ) is shown in Figure
3A. An example of an archaeal genus that was retained from the wild in
captive chimpanzees in the United States (i.e., the genusvadinCA11 ) is shown in Figure 3B. A list of all microbial
genus-level HSSs for each captive NHP population are shown in Table S2.
Comparing HSSs between pairs of captive primate populations indicated
that no microbial genus was humanized in every NHP population (Table
S7). However, replicate captive populations of the same species
displayed highly consistent genus-level patterns of gut microbiota
humanization. The HSSs between two independent captive populations of
chimpanzees were significant positively associated (R2= 0.82; p -value = 5.51e-24), as were the HSSs between two
independent captive populations of doucs (R2 = 0.8;p -value = 8.46e-18). In addition, the HSS of chimpanzees were
significantly associated with those of gorillas (R2 =
0.16; p -value = 0.000871 and R2 = 0.25;p -value = 1.05e-05), but not with those of doucs (Figure 4).
Similar results, in which no genus displayed evidence of humanization in
all captive NHP populations but replicate captive populations of the
same NHP species displayed similar patterns of humanization of microbial
genera, were observed in analyses of a related statistic, Microbiota
Convergence Scores (MCSs) (Supplementary Materials and Methods, Figure
S4, Table S8). Heatmaps of HSSs and MCSs of taxa found in all captive
NHP populations are presented in Figure S5. Qualitatively similar
results, in which HSSs and MCSs were significantly positively associated
between conspecific captive NHP populations but tended to be not
associated or negatively associated between heterospecific captive NHP
populations, were observed in analyses based on data from the American
Gut Project (McDonald et al., 2018) (Supplementary Materials and
Methods; Table S9 and S10).