IAP2-22-413

Mandrills and microbes II: the gut microbiome

The primate gastro-intestinal tract is home to trillions of micro-organisms, which provide their host with essential benefits. In addition to aiding digestion and producing vitamins, gut micro-organisms play a crucial role in the host immune response, protecting the host from infection. Understanding the host-microbe relationship in primates thus has important implications for our understanding of primate health, behaviour, and evolution. With almost 60% of primates threatened with extinction, improving our understanding of their microbiome also has important implications for primate conservation, due to its importance in the diet and immune system. Moreover, because we are primates, understanding the primate microbiome has implications for our understanding of ancestral microbiomes and human evolution.

The project forms part of a long-term study of the behaviour, health, and physiology of a semi-free ranging colony of mandrills (Mandrillus sphinx, a large species of African primate) under naturalistic conditions. It combines microbiology and bioinformatics with the study of life history, behaviour, and immune responses to examine the host-microbe relationship in a social primate.

Mandrills are a particularly intriguing species for this study because of their complex sociality, and reliance on multimodal signalling. They live in unusually large groups, facilitating social transmission of microbiota. These groups are made up of females living in matrilines and males that can be full members of the group, peripheral or solitary. These sex differences in the strength and patterns of social bonds suggest that the factors influencing the composition of the gut microbiome may also differ between the sexes, and between individuals. Mandrills’ brightly coloured facial skin signals dominance in males, and age and fertility in females. Their odour encodes information on sex, rank, relatedness, major histocompatibility genotype, and individual identity. How these signals relate to the bacterial communities in the gut is not yet known.

The project benefits from existing samples and datasets, with which the PhD student can develop and refine their methods and test hypotheses. They will first extract DNA from existing faecal samples and use high-throughput sequencing and bioinformatics to characterise the faecal microbiome of mandrills living under naturalistic conditions. They will use these data and our existing datasets to investigate the following hypotheses:

1. The composition of the faecal microbiome differs predictably with host-specific characteristics (age and maturational stage, sex, dominance rank, reproductive status)
2. The composition of the faecal microbiome is transmitted vertically from mother to offspring.
3. A shared environment facilitates the transmission of microbes. Thus, in social animals, group membership shapes the faecal microbiome.
4. Administration of an anti-parasite treatment affects the composition of the faecal microbiome. Such treatments have a strong influence on the faecal microbiome in humans and laboratory animals and can increase susceptibility to disease.
5. The composition of the faecal microbiome is related to the host’s immunological profile and phenotype.

Based on their findings, and a review of the literature, the student will then design and implement further sampling to address further questions. For example, they might choose to test the hypothesis that social behaviour facilitates bacterial transmission between individuals, the influence of habitat on the faecal microbiome, or the relationships between the faecal microbiomes of the various primate species housed at the CIRMF primate centre (including chimpanzees, endemic sun-tailed monkeys, red-capped mangabeys, and various Cercopithecus species). Alternatively, they may choose to pursue funding applications for additional laboratory methods, including metagenomics.

The project will contribute to our understanding of mammalian health and evolution, the coevolution of hosts and microbes (via collaboration with the Primate Microbiome Project), and the human microbiome (due to our phylogenetic proximity). The project also has the potential to benefit the health and welfare of captive primates and to influence protocols used to release primates into the wild. For example, routine veterinary treatment of captive populations with antiparasite treatments may reduce gut parasites (worms), but if it also reduces gut microbiome biodiversity, it may also alter gut functioning, with potential health implications for both captive populations and those being released into the wild. The knowledge produced by this study could enable release programs to develop protocols for preparing individuals’ gut microbiomes for the challenges of release to maximise their chances of success.

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Image Captions

Mandrill(s) living at the Centre International de Recherches Médicales, Franceville, Gabon.

Methodology

Study subjects: Mandrills are large cercopithecine primates that live in the dense rainforests of Gabon, Equatorial Guinea, Cameroon, and the Democratic Republic of Congo. The CIRMF mandrill colony was founded in 1983 and currently comprises ~120 animals living in three forested enclosures. The animals can be observed daily and are captured annually for a health check.

Biological samples: The student will use existing faecal samples (n = 318, with some individuals sampled multiple times) collected by SK and JMS, complemented with new samples collected from the CIRMF mandrill colony. Training and oversight: BN and JMS.

Behavioural sampling: The student will collect behavioural data on the CIRMF mandrill colony. Training and oversight: JMS.

Laboratory methods: The student will isolate genomic DNA from biological samples that will be sent for high-throughput sequencing (16s/18S/ITS amplicon sequencing and metagenomics). Specific microbial species of interest can be further investigated by qPCR. Training and oversight: LK

Bioinformatics: The student will analyse sequencing data using online tools such as Qiime2TM, and cloud-based computing tools of CLIMB MRC. The student will attend external training courses and additional advice is available from our collaborators at the Institute of Vertebrate Biology, Czech Academy of Sciences. Oversight: LK.

The timeline is flexible, and will depend on the timing of achievement of specific aims.

Project Timeline

Year 1

3 months in Durham (Oct-Dec): Initial training needs analysis to refine needs. Detailed literature reviews on relevant topics (microbial ecology, the primate microbiome, primate health and behavioural ecology).

1 month of initial laboratory and bioinformatics training at HWU (Jan).

3 months in Brno (Feb-Apr): initial laboratory training, extract small number of samples for pilot work and quality checks. Extract all remaining samples and send for amplicon sequencing.

5 months at HWU (May-Sept): Attend data analysis training courses (Training in Introduction to Linux for Genomics; Introduction to Metabarcoding and Metagenomics Analysis). Begin bioinformatic analysis. Submit PhD progression report and undergo examination at 9 months. Present project plans and pilot work at national conferences.

Year 2

6 months (Oct-Mar) in UK for bioinformatic analysis of existing samples to address initial research questions. Use findings to design additional sample collection.

Sample collection in Gabon (April-June).

Extraction, sequencing and bioinformatic analysis of new samples in UK (July-Sep).

Presentations at national conferences.

Year 3

Continue bioinformatic analysis of new samples (Oct-Dec). Use findings to inform further laboratory and bioinformatic analyses. Preparation and submission of manuscripts for publication; presentations at international conferences.

Year 3.5

Revision of manuscripts for publication; writing up dissertation; presentations at international conferences; applications for future posts.

Training
& Skills

The student will develop the following key skills and expertise during the project: teamwork and collaboration in the field and laboratory; ethics and scientific integrity; searching and critically assessing the literature; study design; behavioural sampling; biological sampling and shipping samples internationally; laboratory analysis including sample preparation for sequencing (gDNA extraction and nucleic acid quantification) and PCR/qPCR; data handling and bioinformatic analyses; writing scientific reports; presenting at conferences.

Opportunities to teach and engage with non-academic audiences are available.

Collaboration with Save Gabon’s Primates includes additional relevant training in primate research, welfare, and conservation issues in the field.

References & further reading

• Amato KR. 2019. Missing links: the role of primates in understanding the human microbiome. mSystems. 4: 3 https://doi.org/10.1128/mSystems.00165-19
• Amato KR, Stumpf RM. 2019. Moving forward with the primate microbiome: Introduction to a special issue of the American Journal of Primatology. Am J Primatol. 81:e23060.
• Clayton JB et al. 2016. Captivity humanizes the primate microbiome. PNAS. 113: 10376-10381.
• Easton et al. 2019. The impact of anthelmintic treatment on human gut microbiota based on cross-sectional and pre- and postdeworming comparisons in western Kenya. mBio 10. https://doi.org/10.1128/mBio.00519-19
• Sarkar A et al. 2020. Microbial transmission in animal social networks and the social microbiome. Nat Ecol Evol. 2020:1–16.
• Setchell JM. 2016, Sexual selection and the differences between the sexes in mandrills (Mandrillus sphinx). Am. J. Phys. Anthropol., 159: 105-129.
• Stumpf RM et al. 2016. Microbiomes, metagenomics, and primate conservation: New strategies, tools, and applications. Biological Conservation 199: 56-66.
• Tung J et al. 2015. Social networks predict gut microbiome composition in wild baboons. eLife. 4:e05224.
• Vlčková, K., et al. 2016. Effect of antibiotic treatment on the gastrointestinal microbiome of free-ranging western lowland gorillas (Gorilla g. gorilla). Microb Ecol 72, 943–954

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