An imbalance in the intestinal microbiota affects the onset and progression of various diseases, including infectious diseases, lifestyle-related diseases, and cancer. Therefore, understanding host–microbe interactions in the gut microbiota contributes to the development of the prevention and treatment of these diseases. Typically, antimicrobial-treated mice or gnotobiotic mice are used for research; however, there are costs and ethical issues involved. Here, we outline studies that have used silkworms as alternative animals. Silkworms can be used in experiments with a large number of individuals, especially because the ethical issues are small. Pathological models of infectious diseases and diabetes have been established using silkworms as the experimental animals. These pathological silkworm models are useful for the identification of lactic acid bacteria, which are expected to have preventive effects against infectious diseases and diabetes.

Many approaches to disease and health control have been attempted using intestinal bacteria and probiotics. However, the molecular mechanisms of the interactions between intestinal bacteria and their hosts are still largely unknown. Caenorhabditis elegans (C. elegans) is one of the model organisms that have played an important role in discoveries which garnered three Nobel Prizes. Since the report of prolongevity effects of lactobacilli and bifidobacteria on Caenorhabditis elegans, together with moves to reduce or eliminate mammalian experiments, knowledge on the biological effects of probiotics and beneficial bacteria using Caenorhabditis elegans as an alternative model has been rapidly accumulating. Our understanding of the intestinal microbiota of the wild C. elegans has also progressed. The C. elegans model is expected to be intensively utilized to elucidate intestinal microbiota-host interactions.