Understanding host-microbe interactions in a changing world: drivers and fitness consequences of the gut microbiome in a declining Antarctic pinniped

脊椎动物是大量微生物的栖息地，这些微生物在宿主的生物学和进化中越来越多地成为关键角色。这些微生物群落携带的基因比宿主多得多，并且支持宿主基因组中未编码的功能。因此，“微生物组”，包括微生物本身和它们产生的分子，对宿主的功能至关重要。最丰富和最重要的微生物群落是胃肠道的微生物群落。肠道微生物多样性的减少与人类的许多疾病有关，包括自身免疫性疾病、糖尿病和肥胖。然而，人们对野生脊椎动物种群中肠道微生物与健康之间的关系知之甚少，在野生脊椎动物种群中，较高水平的遗传变异和明显的环境异质性可能调节甚至覆盖肠道微生物组对宿主的任何影响。我们对宿主-微生物相互作用知识的这一重大差距阻碍了我们对复原力和气候变化适应的理解。该项目将利用南极毛皮海豹这一杰出的自然系统，调查野生种群肠道微生物群的健康后果。由于人类活动导致食物供应减少，野生种群的肠道微生物群正在减少。重点关注出生和营养独立之间的关键发育时间窗口，将阐明肠道微生物组的关键内在和外在驱动因素及其与多种健康相关表型（包括生长、生存、应激激素水平、免疫功能和基因表达）的相互作用。具体来说，我们的项目将利用一个独特的“自然实验”和一个完全交叉的重复测量设计来评估两个相互作用的环境压力因素的影响，食物限制和社会密度。此外，最近开发的单核苷酸多态性阵列将允许对宿主基因型的调节作用进行稳健的评估，包括可遗传的遗传变异和遗传质量，表达为近亲繁殖和免疫遗传多样性。我们假设食物供应减少会降低肠道微生物多样性，增加黏液溶解和促炎类群的流行，对宿主的健康产生负面影响。这些影响在遗传质量差的个体中可能特别明显，他们在控制有害微生物方面可能不太有效，以及在压力大、密度高的条件下。总而言之，该项目将结合丰富的基于个体的生活史和表型数据与多组学方法，对正在衰退的顶级捕食者的宿主-微生物相互作用产生前所未有的详细和多层次的机制见解。这对于了解肠道微生物是否会加剧（或缓冲）气候变化的影响至关重要，并对预测长期人口趋势和管理南大洋生态系统具有直接意义。

Vertebrates are inhabited by vast numbers of microorganisms that are increasingly emerging as key players in their host’s biology and evolution. These microbial communities carry orders of magnitude more genes than their hosts and support functions that are not encoded in the host’s genome. Consequently, the ‘microbiome’, which includes both the microbes themselves and the molecules they produce, is of fundamental importance to host function. The richest and arguably most important microbial communities are those of the gastrointestinal tract. Reduced gut microbial diversity has been linked to many diseases in humans including autoimmune disorders, diabetes and obesity. However, little is known about the relationship between gut microbes and health in wild vertebrate populations, where higher levels of genetic variation and pronounced environmental heterogeneity may modulate or even override any effects of the gut microbiome on the host. This major gap in our knowledge of host-microbiome interactions hinders our understanding of resilience and climate change adaptation. This project will exploit an outstanding natural system, Antarctic fur seals, to investigate the fitness consequences of the gut microbiome in a wild population that is declining in response to anthropogenic reductions in food availability. Focusing on the critical developmental time window between birth and nutritional independence, it will elucidate the effects of key intrinsic and extrinsic drivers on the gut microbiome and its interplay with multiple fitness relevant phenotypes including growth, survival, stress hormone levels, immune function and gene expression. Specifically, our project will exploit a unique ‘natural experiment’ and a fully crossed repeated measures design to evaluate the effects of two interacting environmental stressors, food limitation and social density. Furthermore, a recently developed single nucleotide polymorphism array will allow robust evaluation of the modulating effects of host genotype, including heritable genetic variation and genetic quality, expressed as inbreeding and immunogenetic diversity. We hypothesise that reduced food availability will lower gut microbial diversity and increase the prevalence of mucolytic and proinflammatory taxa, negatively impacting host fitness. These effects may be especially pronounced among individuals of poor genetic quality, who may be less effective at controlling harmful microbes, as well under stressful, high density conditions. In summary, this project will combine rich individual-based life-history and phenotypic data with multi-omics approaches to produce unprecedentedly detailed and multi-layered mechanistic insights into host-microbe interactions in a declining top predator. This is essential for understanding whether gut microbes could exacerbate (or buffer) climate change impacts, and has direct implications for predicting long-term population trends and managing the Southern Ocean ecosystem.