The Nonbacterial Microbiome: Fungal and Viral Contributions to the Preterm Infant Gut in Health and Disease.

The intestinal microbiome is frequently implicated in necrotizing enterocolitis (NEC) pathogenesis. While no particular organism has been associated with NEC development, a general reduction in bacterial diversity and increase in pathobiont abundance has been noted preceding disease onset. However, nearly all evaluations of the preterm infant microbiome focus exclusively on the bacterial constituents, completely ignoring any fungi, protozoa, archaea, and viruses present. The abundance, diversity, and function of these nonbacterial microbes within the preterm intestinal ecosystem are largely unknown. Here, we review findings on the role of fungi and viruses, including bacteriophages, in preterm intestinal development and neonatal intestinal inflammation, with potential roles in NEC pathogenesis yet to be determined. In addition, we highlight the importance of host and environmental influences, interkingdom interactions, and the role of human milk in shaping fungal and viral abundance, diversity, and function within the preterm intestinal ecosystem.