Evolution of extreme stomach pH in bilateria inferred from gastric alkalization mechanisms in basal deuterostomes

The stomachs of most vertebrates operate at an acidic pH of 2 generated by the gastric H+/K+-ATPase located in parietal cells. The acidic pH in stomachs of vertebrates is believed to aid digestion and to protect against environmental pathogens. Little attention has been placed on whether acidic gastric pH regulation is a vertebrate character or a deuterostome ancestral trait. Here, we report alkaline conditions up to pH 10.5 in the larval digestive systems of ambulacraria (echinoderm + hemichordate), the closest relative of the chordate. Microelectrode measurements in combination with specific inhibitors for acid-base transporters and ion pumps demonstrated that the gastric alkalization machinery in sea urchin larvae is mainly based on direct H+ secretion from the stomach lumen and involves a conserved set of ion pumps and transporters. Hemichordate larvae additionally utilized HCO3- transport pathways to generate even more alkaline digestive conditions. Molecular analyses in combination with acidification experiments supported these findings and identified genes coding for ion pumps energizing gastric alkalization. Given that insect larval guts were also reported to be alkaline, our discovery raises the hypothesis that the bilaterian ancestor utilized alkaline digestive system while the vertebrate lineage has evolved a strategy to strongly acidify their stomachs.

多数脊椎动物的胃部处于pH为2的酸性环境，该酸性环境由壁细胞中的胃H+/K+-ATP酶（gastric H+/K+-ATPase）催化产生。学界普遍认为，脊椎动物胃部的酸性环境有助于消化，并可抵御环境中的病原体。此前鲜有研究关注胃部酸性pH调控究竟是脊椎动物的特有特征，还是后口动物（deuterostome）的祖先性状。本研究报道了步带动物（ambulacraria）的幼虫消化系统中存在最高可达pH 10.5的碱性环境，该类群包含棘皮动物（echinoderm）与半索动物（hemichordate），是脊索动物（chordate）的近亲。通过微电极测量结合酸碱转运体与离子泵特异性抑制剂实验，研究证实海胆幼虫的胃部碱化机制主要依赖于胃腔直接分泌H+，并涉及一套保守的离子泵与转运体系统。半索动物幼虫则额外利用碳酸氢根（HCO3-）转运通路，以形成碱性更强的消化系统环境。分子分析结合酸化实验验证了上述结论，并鉴定出了为胃部碱化供能的离子泵编码基因。鉴于已有研究报道昆虫幼虫肠道也呈碱性，本研究的发现提出如下假说：两侧对称动物（bilaterian）的祖先拥有碱性消化系统，而脊椎动物演化支则进化出了显著酸化胃部的策略。