Captivity humanizes the primate microbiome

Abstract

The primate gastrointestinal tract is home to trillions of bacteria, whose composition is associated with numerous metabolic, autoimmune, and infectious human diseases. Although there is increasing evidence that modern and Westernized societies are associated with dramatic loss of natural human gut microbiome diversity, the causes and consequences of such loss are challenging to study. Here we use nonhuman primates (NHPs) as a model system for studying the effects of emigration and lifestyle disruption on the human gut microbiome. Using 16S rRNA gene sequencing in two model NHP species, we show that although different primate species have distinctive signature microbiota in the wild, in captivity they lose their native microbes and become colonized with Prevotella and Bacteroides, the dominant genera in the modern human gut microbiome. We confirm that captive individuals from eight other NHP species in a different zoo show the same pattern of convergence, and that semicaptive primates housed in a sanctuary represent an intermediate microbiome state between wild and captive. Using deep shotgun sequencing, chemical dietary analysis, and chloroplast relative abundance, we show that decreasing dietary fiber and plant content are associated with the captive primate microbiome. Finally, in a meta-analysis including published human data, we show that captivity has a parallel effect on the NHP gut microbiome to that of Westernization in humans. These results demonstrate that captivity and lifestyle disruption cause primates to lose native microbiota and converge along an axis toward the modern human microbiome.

Keywords: dietary fiber; dysbiosis; human microbiome; microbial ecology; primate microbiome.

Fig. 1.

The captive primate microbiome converges toward the modern human microbiome. Principal coordinates plot of unweighted UniFrac distances showing ecological distance between gut microbial communities in wild, semicaptive (from a sanctuary), and captive NHPs, as well as non-Westernized humans, and humans living in the United States (i.e., Westernized). All samples were obtained with the same protocol for V4 16S rRNA sequencing. Although in wild populations the douc and howler microbiomes are highly distinctive, captivity causes them to converge toward the same composition. Semicaptive doucs (green) fall in between wild and captive doucs along the same axis of convergence. The axis of convergence continues toward non-Westernized human populations (Malawi and Venezuela), and finally to the modern US human microbiome. One howler individual resembling wild howlers was sampled after only 2 d in captivity, indicating that the transition to the captive microbiome state requires more than 2 d. Semicaptive doucs born in the wild have similar microbiomes to their captivity-born counterparts, indicating that transition to captivity from the wild is sufficient to produce the captivity-related microbiome.

Fig. 2.

Discriminative taxa by species and captivity status. Highly predictive taxa for discriminating the captive, semicaptive, wild douc, and wild howler groups. Predictive taxa included are those with a 0.001 mean decrease in accuracy when removed as determined by the random forests classifier. The classifier was able to correctly predict the group label for unseen samples for all but one sample (99.6% accuracy). Semicaptive individuals show an overlap between some of the wild douc genera and some of the captive animal genera. Captive NHPs contain large blocks of bacterial genera that are absent from wild NHPs, and vice versa, indicating a massive shift in taxonomic composition between the populations. Although wild howlers tended to overlap more with captive NHPs than did the wild doucs, both the doucs and howlers lose most of their native signature gut bacteria in captivity.

Fig. 3.

Captivity reduces native primate microbiota. (A) Bar plot of mean and spread of gut microbial biodiversity, as measured by the number of species-like OTUs in the gut microbiome, of wild, semicaptive, and captive douc populations of NHPs, using the Chao1 estimator of total OTU richness. This indicates a significant loss of biodiversity from wild populations to semicaptive populations, and again from semicaptive to captive. Error bars indicate SD, and asterisks denote significance at *P < 0.05, **P < 0.01, and ***P < 0.001. (B) Standard box plot of microbiome variation (unweighted UniFrac distance) explained by different experimental factors, showing that captivity in general is associated with a greater change in microbiome state than variation in host species, zoological institution, or individual.

Fig. 4.

Dietary fiber and gut microbiome in NHPs. (A) Mean ecological similarity of a given individual douc’s microbiome to all wild douc microbiomes, plotted against that individual’s estimated dietary fiber content (black); same, but showing mean ecological similarity to humans (blue). Doucs consuming more fiber more closely resemble wild doucs in their microbiome; doucs consuming less fiber more closely resemble humans. (B) The same samples plotted in Fig. 1, colored by host species. Also shown is the primary axis of correlation of chloroplast relative abundance, a proxy measurement for dietary raw plant content, with sample positions. A smoothed local regression curve for chloroplast ratio (i.e., relative abundance) along the primary axis of variation shows decreasing raw plant consumption from wild, to semicaptive, to captive primates, with almost no raw plant consumption in the humans or US captive primates. (C) Fraction of whole-genome shotgun data aligning at 97% identity to known plant genomes for 14 captive individuals (9 douc, 5 howler) and 16 wild individuals (8 douc, 8 howler). Wild individuals have a high fraction of plant DNA in their stool; captive individuals have almost none, with the exception of a single outlier individual who was recently rescued from the wild for treatment of electrical burns (also an outlier in Fig. 1).

Fig. 5.

Captive primates acquire Bacteroides and Prevotella, the dominant genera in the modern human gut microbiome. A bee swarm plot of the arc-sine square root relative abundance of bacterial genera Bacteroides and Prevotella, the two dominant modern human gut microbiome genera, shown in wild, semicaptive, and captive NHPs, as well as in non-Westernized and Westernized humans. As populations shift toward the captive state, their microbiomes become colonized by dominant human gut bacterial genera.