Unveiling the viral dimension: The paediatric gut virome as a key modulator of gastrointestinal metabolic, and neurodevelopmental health

Figure 6 The developmental pathway of functional gastrointestinal disorders via virome-mediated mechanisms. This flowchart illustrates how early-life viral encounters can lead to chronic functional gastrointestinal disorders (FGIDs) through three interconnected pathways. Immune programming: Viral infections create a “Sensitization” window, leading to persistent signaling via toll-like receptors and epigenetic changes in immune cells, permanently lowering the threshold for immune activation. Low-grade inflammation: Acute insults leave a “molecular hangover” of sub-clinical inflammation. Inflammatory mediators like histamine directly sensitize nociceptors, resulting in peripheral sensitization where the gut becomes hyper-reactive. Altered signaling: Virome disturbances disrupt the gut-immune-neural axis. This involves direct viral-neural crosstalk and disrupted feedback loops due to microbial instability, leading to “noisy” and exaggerated signaling. All three pathways converge to cause visceral hypersensitivity, the hallmark of FGIDs. In a subset of children, a failure to “reset” this axis after the initial infection results in a chronic functional pain disorder, such as post-infectious irritable bowel syndrome. FGID: Functional gastrointestinal disorders; IBS: Irritable bowel syndrome; TLR: Toll-like receptors.