Chronic diarrhea is a messy disease that can even be fatal. In addition to being widespread in humans, it’s common in captive rhesus macaques, which are important research animals. However, the causes of chronic diarrhea are often murky. To learn more, researchers recently compared the gut microbiomes of rhesus macaques with and without chronic diarrhea. According to metagenomic sequencing, sick macaques had significant depletion of Lactobacillus bacteria but increased abundance of opportunistic pathogens and bacteria that degrade the protective intestinal mucus layer. Metabolic pathways related to virulence factor synthesis were also activated in macaques with diarrhea, whereas beneficial short-chain fatty acid pathways were enhanced in asymptomatic macaques. In addition, compared with those of asymptomatic macaques, the gut bacteria of sick macaques had higher expression of antibiotic resistance genes (ARGs) and greater resistance to most tested antibiotics. Further analyses suggested that nonhuman primates like macaques are suitable models for research on chronic diarrhea in humans who consume non-westernized diets. Although more research is needed, the results clarify the role of the microbiome in chronic diarrhea in macaques and may help improve diarrhea prevention and treatment in these research animals and in certain human populations.