Drosophila-associated bacteria differentially shape the nutritional requirements of their host during juvenile growth

The interplay between nutrition and the microbial communities colonizing the gastrointestinal tract (i.e., gut microbiota) determines juvenile growth trajectory. Nutritional deficiencies trigger developmental delays, and an immature gut microbiota is a hallmark of pathologies related to childhood undernutrition. However, how host-associated bacteria modulate the impact of nutrition on juvenile growth remains elusive. Here, using gnotobiotic Drosophila melanogaster larvae independently associated with Acetobacter pomorumWJL (ApWJL) and Lactobacillus plantarumNC8 (LpNC8), 2 model Drosophila-associated bacteria, we performed a large-scale, systematic nutritional screen based on larval growth in 40 different and precisely controlled nutritional environments. We combined these results with genome-based metabolic network reconstruction to define the biosynthetic capacities of Drosophila germ-free (GF) larvae and its 2 bacterial partners. We first established that ApWJL and LpNC8 differentially fulfill the nutritional requirements of the ex-GF larvae and parsed such difference down to individual amino acids, vitamins, other micronutrients, and trace metals. We found that Drosophila-associated bacteria not only fortify the host’s diet with essential nutrients but, in specific instances, functionally compensate for host auxotrophies by either providing a metabolic intermediate or nutrient derivative to the host or by uptaking, concentrating, and delivering contaminant traces of micronutrients. Our systematic work reveals that beyond the molecular dialogue engaged between the host and its bacterial partners, Drosophila and its associated bacteria establish an integrated nutritional network relying on nutrient provision and utilization.营养与定植于胃肠道的微生物群落（即肠道菌群（gut microbiota））之间的相互作用，决定了幼虫的生长轨迹。营养缺乏可引发发育迟缓，而未成熟的肠道菌群是儿童营养不良相关病理的标志性特征。然而，宿主相关细菌如何调控营养对幼虫生长的影响，目前仍尚不明确。本研究采用分别定植有两种模式果蝇共生细菌——醋杆菌pomorum菌株WJL（Acetobacter pomorumWJL，简称ApWJL）与植物乳杆菌NC8（Lactobacillus plantarumNC8，简称LpNC8）的悉生（gnotobiotic）黑腹果蝇（Drosophila melanogaster）幼虫作为实验材料，基于40种不同且精准可控的营养环境下的幼虫生长情况，开展了大规模系统性营养筛选实验。我们将该实验结果与基于基因组的代谢网络重建分析相结合，明确了无菌（germ-free，GF）黑腹果蝇幼虫及其两种共生细菌的生物合成能力。我们首先证实，ApWJL与LpNC8可差异化满足无菌果蝇幼虫的营养需求，并将这种差异拆解至单个氨基酸、维生素、其他微量营养素及痕量金属层面。研究发现，果蝇共生细菌不仅可为宿主饮食补充必需营养素，在特定场景下，还可通过向宿主提供代谢中间产物或营养衍生物，或是通过摄取、富集并递送微量营养素中的痕量污染物，功能性代偿宿主的营养缺陷。本系统性研究揭示，除宿主与其共生细菌之间的分子互作之外，果蝇与其共生细菌还构建出一套依赖于营养供给与利用的整合性营养网络。