<b>Pathobiont and symbiont coordination maintains microbiota homeostasis through Malpighian tubules-gut countercurrent flow in the fly</b><b> </b><b><i>Bactrocera dorsalis</i></b>

Host-gut microbiota interactions are more complex than good and bad. Both gut symbiotic bacteria and pathobionts can provide essential functions to their host in one scenario and yet be detrimental to host health in another. So, these gut-dwelling bacteria must be tightly controlled to avoid harmful effects on the host. However, how pathobionts and other symbiotic bacteria coordinate to establish a host immune defense system remains unclear. Here, using a Tephritidae fruit fly <i>Bactrocera dorsalis</i>, we report that both pathobionts and other gut symbiotic bacteria release tyramine, which is recognized by the host insects. These tyramines induce the formation of conserved Malpighian tubules-gut countercurrent flow upon bacterial infection, which requires tyramine receptors and aquaporins. At the same time, pathobionts but not other gut symbiotic bacteria induce the generation of ROS, which are preserved by the countercurrent flow, promoting bacteria elimination through increasing gut peristalsis. More importantly, our results show that the Malpighian tubules-gut countercurrent flow maintains proper microbiota composition. Our work suggests a model where pathobiont-induced ROS are preserved by both pathobionts and symbiotic bacteria-induced Malpighian tubules-gut countercurrent flow. Furthermore, our work provides a Malpighian tubules-gut interaction that ensures efficient maintenance of the gut microbiota.宿主与肠道菌群的互作（Host-gut microbiota interactions）远非“有益/有害”的二元对立所能概括。无论是肠道共生细菌（gut symbiotic bacteria）还是条件致病菌（pathobionts），在特定情境下均可为宿主提供必需的生理功能，而在另一情境下则会对宿主健康造成损害。因此，这些定植于肠道的细菌必须受到严格调控，以避免对宿主产生有害影响。然而，条件致病菌与其他肠道共生细菌如何协同构建宿主免疫防御系统，目前仍不明晰。本研究以实蝇科（Tephritidae）果实蝇——橘小实蝇（Bactrocera dorsalis）为实验模型，发现条件致病菌与其他肠道共生细菌均可释放酪胺（tyramine），该物质可被宿主昆虫识别。上述酪胺可在细菌感染时诱导宿主形成保守的马氏管-肠道逆流系统（Malpighian tubules-gut countercurrent flow），该过程依赖于酪胺受体（tyramine receptors）与水通道蛋白（aquaporins）。与此同时，仅条件致病菌而非其他肠道共生细菌可诱导活性氧（ROS, Reactive Oxygen Species）的产生，该活性氧可被上述逆流系统留存，并通过增强肠道蠕动促进细菌清除。更为重要的是，本研究结果显示，马氏管-肠道逆流系统可维持肠道菌群的稳态组成。本研究提出了一种模型：条件致病菌诱导产生的活性氧，可由条件致病菌与共生细菌共同诱导的马氏管-肠道逆流系统所留存。此外，本研究揭示了一种马氏管-肠道互作机制，可确保肠道菌群的高效稳态维持。