There is a complex multitude of interactions occurring between the members of the intestinal microbiome, and between the microbiome and host cells. These interactions represent an intricate dance, balancing homeostasis and compromised immunity. A small but mighty population of chemosensory cells lies at this vibrant intersection of microbiome dynamics and host-microbe interactions: the tuft cell (TC). TCs were discovered in the mid-20th century, but their function in sensing and responding to the intestinal luminal environment was not elucidated until 2016. TCs have been a major focus of immunological research since, though much of the literature on intestinal TCs has focused on the small intestine, the role of the microbiome in modulating TC dynamics in the large intestine and the relevance of this pathway to infections is unknown. Multiple methods of microbiome modulation are utilized to demonstrate that a microbiome rich in succinate-producing bacteria can drive colonic TC hyperplasia and type II cytokine production. This phenotype resulting from a succinate-producing microbiome is not seen in other intestinal compartments, highlighting a novel mechanism for TC-microbe interaction in the colon, the heart of intestinal microbial richness and diversity. Microbiome-driven colonic TC hyperplasia is demonstrated to protect against morbidity and mortality from infection with the colonic pathogen, Clostridioides difficile, and depends on microbially produced succinate and Pou2f3 TCs. This work expands understanding of how and where TCs sense alterations in the microbiome, the role of microbes and their metabolites in colonic TC communication, and the potential for harnessing TC-microbial interactions for promoting intestinal homeostasis.