Enchained growth and cluster dislocation: A possible mechanism for microbiota homeostasis

Immunoglobulin A is a class of antibodies produced by the adaptive immune system and secreted into the gut lumen to fight pathogenic bacteria. We recently demonstrated that the main physical effect of these antibodies is to enchain daughter bacteria, i.e. to cross-link bacteria into clusters as they divide, preventing them from interacting with epithelial cells, thus protecting the host. These links between bacteria may break over time. We study several models using analytical and numerical calculations. We obtain the resulting distribution of chain sizes, that we compare with experimental data. We study the rate of increase in the number of free bacteria as a function of the replication rate of bacteria. Our models show robustly that at higher replication rates, bacteria replicate before the link between daughter bacteria breaks, leading to growing cluster sizes. On the contrary at low growth rates two daughter bacteria have a high probability to break apart. Thus the gut could produce IgA against all the bacteria it has encountered, but the most affected bacteria would be the fast replicating ones, that are more likely to destabilize the microbiota. Linking the effect of the immune effectors (here the clustering) with a property directly relevant to the potential bacterial pathogeneicity (here the replication rate) could avoid to make complex decisions about which bacteria to produce effectors against.

免疫球蛋白A（Immunoglobulin A）是一类由适应性免疫系统（adaptive immune system）产生的抗体，可被分泌至肠道腔（gut lumen）以对抗病原菌（pathogenic bacteria）。我们近期的研究表明，这类抗体的核心物理效应是将子代细菌（daughter bacteria）连接成链：即当细菌分裂时，将其交联为团簇，阻断细菌与上皮细胞（epithelial cells）的相互作用，从而保护宿主。细菌间的这类交联会随时间逐渐断裂。我们采用解析计算与数值模拟（analytical and numerical calculations）相结合的方法对多种模型展开研究，得到了链状团簇的尺寸分布，并将其与实验数据进行比对。我们还分析了游离细菌（free bacteria）数量的增长速率随细菌复制速率（replication rate）的变化关系。我们的模型稳健地显示：当复制速率较高时，细菌会在子代细菌间的交联断裂前完成分裂，进而导致团簇尺寸不断增大；反之，当生长速率较低时，两个子代细菌有极高概率发生分离。因此，肠道可针对其曾接触过的所有细菌产生免疫球蛋白A，但受影响最显著的将是快速复制的细菌——这类细菌更易破坏微生物群（microbiota）的稳态。将免疫效应物（immune effectors，此处为团簇交联效应）与细菌潜在致病性（pathogeneicity）直接相关的特性（此处为复制速率）相联系，可避免在“针对哪些细菌产生免疫效应物”这一问题上做出复杂决策。