Infant diarrheal disease impedes maturation of the microbiome and is linked to a diverse set of novel yet to be cultured Campylobacter species - MAGs

Diarrheal diseases remain one of the leading causes of death for children under 5 globally, disproportionately impacting those living in low- and middle-income countries (LMIC). Campylobacter spp. is a zoonotic pathogen found in many animal species and is one of the leading causes of food-borne infection in humans, and yet to be cultured Campylobacter contribute to the total burden in diarrheal disease in LMIC children thus hampering interventions. We performed microbiome profiling and metagenomic genome assembly on samples collected from over 100 infant rhesus macaques longitudinally and during cases of clinical diarrhea within the first year of life. Acute diarrhea was associated with taxonomic and functional shifts of the infant gut microbiome and resulted in a chronic state of microbiome immaturity well beyond the resolution of symptoms. One of the major drivers of these changes was the increased relative abundance of Campylobacter which we investigated further using metagenomic assembled genomes (MAGs). We constructed 36 Campylobacter MAGs, many of which fell within 4 yet to be cultured species. Finally, we used the uncultured Campylobacter MAGs assembled from infant macaques with publicly available human metagenomes to show that these uncultured species are also found in human fecal samples from LMIC. These data highlight the importance unculturable Campylobacter spp. as an important target for reducing disease burden in LMIC children.