Humans and many other hosts establish a diverse community of beneficial microbes anew each generation. The order and identity of incoming symbionts is critical for health, but what determines the success of the assembly process remains poorly understood. Here we develop ecological theory to identify factors important for microbial community assembly. Our method maps out all feasible pathways for the assembly of a given microbiome—with analogies to the mutational maps underlying fitness landscapes in evolutionary biology. Building these “assembly maps” reveals a tradeoff at the heart of the assembly process. Ecological dependencies between members of the microbiota make assembly predictable—and can provide metabolic benefits to the host—but these dependencies may also create barriers to assembly. This effect occurs because interdependent species can fail to establish when each relies on the other to colonize first. We support our predictions with published data from the assembly of the preterm infant microbiota, where we find that ecological dependence is associated with a predictable order of arrival. Our models also suggest that hosts can overcome barriers to assembly via mechanisms that either promote the uptake of multiple symbiont species in one step or feed early colonizers. This predicted importance of host feeding is supported by published data on the impacts of breast milk in the assembly of the human microbiome. We conclude that both microbe to microbe and host to microbe interactions are important for the trajectory of microbiome assembly.

Microplastics (MP) contamination in food and water poses significant health risks. While microbes that form biofilm show potential for removing MP from the environment, no methods currently exist to eliminate these non-degradable MP from the human body. In this study, we propose using probiotics to adsorb and remove ingested MP within the gut. We conducted a comprehensive evaluation of 784 bacterial strains to assess their ability to adsorb 0.1 μm polystyrene particles using a high-throughput screening method. Among the tested strains, Lacticaseibacillus paracasei DT66 and Lactiplantibacillus plantarum DT88 exhibited optimal adsorption in vitro and were effective across various MP types. In an animal model, mice treated with these probiotics demonstrated a 34% increase in PS excretion rates and a 67% reduction in residual polystyrene (PS) particles within the intestine. Additionally, administration of Lactiplantibacillus plantarum DT88 mitigated PS-induced intestinal inflammation. Together, our findings demonstrate a novel probiotic strategy for addressing MP-associated health risks, emphasizing the potential of strain-specific probiotics to remove MP from the gut environment.

The coat protein I (COPI) complex mediates retrograde trafficking from the Golgi to the endoplasmic reticulum (ER). Five siblings with persistent bacterial and viral infections and defective humoral and cellular immunity had a homozygous p.K652E mutation in the γ1 subunit of COPI (γ1-COP). The mutation disrupts COPI binding to the KDEL receptor and impairs the retrieval of KDEL-bearing chaperones from the Golgi to the ER. Homozygous Copg1^K652E mice had increased ER stress in activated T and B cells, poor antibody responses, and normal numbers of T cells that proliferated normally, but underwent increased apoptosis upon activation. Exposure of the mutants to pet store mice caused weight loss, lymphopenia, and defective T cell proliferation that recapitulated the findings in the patients. The ER stress-relieving agent tauroursodeoxycholic acid corrected the immune defects of the mutants and reversed the phenotype they acquired following exposure to pet store mice. This study establishes the role of γ1-COP in the ER retrieval of KDEL-bearing chaperones and thereby the importance of ER homeostasis in adaptive immunity.