Diversity of macaque microbiota compared to the human counterparts

Chen, Zigui; Yeoh, Yun Kit; Hui, Michael K.; Wong, Pak-Kin; Chan, Max Kam-Kwan; Ip, Margaret; Yu, Jun; Burk, Robert D.; Chan, Francis K.L.; Chan, Paul Kay Sheung

doi:10.1038/s41598-018-33950-6

Cited by 46 publications

(55 citation statements)

References 78 publications

(79 reference statements)

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“…Yatsunenko et al reported that observed OTUs increased with age in all three populations [12]. In a recent study of non-captive rhesus macaques Chen et al reported that male adults had significant higher Shannon index than male juvenile [27]. However, under a well-controlled environment provided by captivity, alpha diversity changes are probably smoothed out.…”

Section: Discussionmentioning

confidence: 99%

Dynamic age-associated changes and their driver microbes in healthy gut microbiota of captive crab-eating macaques

Wei

Rao²,

Tang³

et al. 2020

Preprint

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Background: Previous population studies have indicated age-associated changes in the gut microbiota. However, the actual age effects on microbiota are inevitably confounded by varying environmental factors such as diets and antibiotic use in the populations. Captive crab-eating macaques reared in a well-controlled environment can provide a useful model to recapitulate dynamic age-associated changes in the healthy primate gut microbiota.Results: We show evidence supporting lifelong age-associated changes in the healthy gut microbiota of captive macaques. The Firmicutes to Bacteroidetes ratio and beta diversity but not alpha diversity changed significantly with age. The most significantly age-associated genera were mainly composed of commensals, such as Faecalibacterium . Unexpectedly, a subset of the age-associated microbes were suspicious pathogens such as Helicobacter and Campylobacter , which were enriched in infant macaques, and possibly associated with gut mucosa development. These age-associated microbes were main contributors to the gut microbiota networks. Importantly, topology analysis showed that connectivity of these networks changed with age, and its rapid decrease in elderly macaques might indicate altered microbial interactions associated with host aging. Prevotella 9 , one of the most abundant age-associated genera, was the driver responsible for the gut microbiota maturation from infants to young adults. In adults, Rikenellaceae RC9 gut group and Megasphaera were two key drivers that continuously played an active role in driving microbial community changes of across different stages of adulthood. We also showed evidence of age-associated changes in gut microbial phenotypes and functions, in particular pathways of immunomodulatory metabolite synthesis, and metabolism of lipids and carbohydrates. The driver microbes were key players involved in these functions.Conclusions: Our current study in captive macaques demonstrate evident age-associated changes during the lifelong process of healthy gut microbiota development. The enrichment of suspicious pathogens in healthy infant macaques might indicate the importance of appropriate exposure to these microbes for the developing immune system. The current study provides new insights into the pivotal role of driver microbes and microbial interactions in gut microbiota, and further underlines the importance of network analysis in microbiome studies. Our findings also provide a baseline for better understanding of disease-related changes in the primate gut microbiota.

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Section: Discussionmentioning

confidence: 99%

Dynamic age-associated changes and their driver microbes in healthy gut microbiota of captive crab-eating macaques

Wei

Rao²,

Tang³

et al. 2020

Preprint

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“…In our male animals, notable urethral taxa include Prevotella , Porphyromona , and Ezakiella , have all been previously associated with the urinary tract microbiome of adult men ( 23–25 ). Prevotella has been previously detected in the genital microbiome of healthy female rhesus monkeys indicating that this genus plays a residential role in the rhesus monkeys genital microbiome ( 10 ). In humans, some species of Prevotella have been associated with disease states (e.g., bacterial vaginosis ( 26 )) while other species can be found in clinically healthy women (e.g., post-partum, ( 21 )).…”

Section: Discussionmentioning

confidence: 99%

“…Many studies have laid the groundwork in characterizing the genital microenvironment of various species of captive and wild NHPs ( 2, 10–12 ). Unlike the vaginal microbiome of humans, which is often dominated by a single Lactobacillus species ( 13 ), NHPs, including rhesus monkeys, harbor a diverse set of vaginal microbes ( 2, 11 ).…”

Section: Introductionmentioning

confidence: 99%

The influence of sex on the urogenital microbiome of rhesus monkeys

Lueert

Roos

et al. 2019

Preprint

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14The vaginal microbiome of nonhuman primates (NHPs) differs substantially from humans 15 in terms of Lactobacillus abundance, overall taxonomic diversity, and vaginal pH. Given 16 these differences, it remains unclear in what way the NHP genital microbiome protects 17 against pathogens, in particular sexually transmitted diseases. Considering the effect that 18 microbiome variations can have on disease acquisition and outcome, we examined 19 endogenous and exogenous factors that influence the urogenital microbiome of captive 20 rhesus monkeys. The male urethral (n=37) and vaginal (n=194) microbiome of 11 21 breeding groups were examined in a cross-sectional study. During lactation and 22 menstruation, the vaginal microbiome becomes significantly more diverse and more 23 similar to the microbes observed in the male urethra. Group association and cage-mate 24 (sexual partners) relationships were additionally associated with significant differences in 25 the urogenital microbiome. Our results demonstrate that microbiome considerations are 26 necessary in order to make informed selection of NHPs as translational animal models. 27

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“…This is because the genetic relatedness of primates, and hence greater physiological and microbiological similarity to humans, requires less interpolation compared to other animal model systems [28][29][30][31]. Mice are a common experimental model system used in preclinical studies of human drugs and vaccines.…”

Section: Study Rationalementioning

confidence: 99%

“…However, the NHP model is better suited to answering key questions about Bt OMV vaccine efficacy and safety in humans. This is because the genetic relatedness of primates, and hence greater physiological and microbiological similarity to humans, requires less interpolation compared to other animal model systems [28][29][30][31]. Therefore, the use of NHPs de-risks the development pathway for Bt-OMV vaccine by providing assurance that the NHP microbiome and histological integrity of the GI tract, and other associated tissues, are not adversely affected following immunization.…”

Section: Study Rationalementioning

confidence: 99%

Use of bioengineered human commensal gut bacteria-derived microvesicles for mucosal plague vaccine delivery and immunization

Carvalho

Miquel-Clopés

Wegmann

et al. 2019

Clinical &Amp; Experimental Immunology

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Summary Plague caused by the Gram‐negative bacterium, Yersinia pestis, is still endemic in parts of the world today. Protection against pneumonic plague is essential to prevent the development and spread of epidemics. Despite this, there are currently no licensed plague vaccines in the western world. Here we describe the means of delivering biologically active plague vaccine antigens directly to mucosal sites of plague infection using highly stable microvesicles (outer membrane vesicles; OMVs) that are naturally produced by the abundant and harmless human commensal gut bacterium Bacteroides thetaiotaomicron (Bt). Bt was engineered to express major plague protective antigens in its OMVs, specifically Fraction 1 (F1) in the outer membrane and LcrV (V antigen) in the lumen, for targeted delivery to the gastrointestinal (GI) and respiratory tracts in a non‐human primate (NHP) host. Our key findings were that Bt OMVs stably expresses F1 and V plague antigens, particularly the V antigen, in the correct, immunogenic form. When delivered intranasally V‐OMVs elicited substantive and specific immune and antibody responses, both in the serum [immunoglobulin (Ig)G] and in the upper and lower respiratory tract (IgA); this included the generation of serum antibodies able to kill plague bacteria. Our results also showed that Bt OMV‐based vaccines had many desirable characteristics, including: biosafety and an absence of any adverse effects, pathology or gross alteration of resident microbial communities (microbiotas); high stability and thermo‐tolerance; needle‐free delivery; intrinsic adjuvanticity; the ability to stimulate both humoral and cell‐mediated immune responses; and targeting of primary sites of plague infection.

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Diversity of macaque microbiota compared to the human counterparts

Cited by 46 publications

References 78 publications

Dynamic age-associated changes and their driver microbes in healthy gut microbiota of captive crab-eating macaques

Dynamic age-associated changes and their driver microbes in healthy gut microbiota of captive crab-eating macaques

The influence of sex on the urogenital microbiome of rhesus monkeys

Use of bioengineered human commensal gut bacteria-derived microvesicles for mucosal plague vaccine delivery and immunization

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