Necrotizing enterocolitis (NEC) remains a life-threatening challenge in neonatology, primarily due to the lack of sensitive early biomarkers that precede overt clinical and radiological signs. This Perspective proposes a hypothesis-generating, non-invasive early-warning framework by integrating quantitative tongue image analysis with modern pathophysiological insights. We hypothesize a dynamic association between tongue phenotypic changes (e.g., a transition from pale to purplish color) and the progression of dysbiosis and intestinal microcirculatory disturbance, which correspond to two distinct but potentially complementary pathways. The proposed biological link rests on evidence for the candidate oral–gut microbial relationship, with such evidence derived primarily from adult and non-neonatal studies; gut dysbiosis—known to precede NEC—may be associated with changes in the tongue-coating microbiome, offering a potential remote yet accessible window into intestinal health. We outline a three-phase translational research roadmap: (I) prospective discovery of tongue-image biomarkers and establishment of dynamic baselines for each infant, (II) development of an exploratory machine-learning-based risk prediction model, and (III) mechanistic exploration using multi-omics approaches and animal models. Critically, we propose three testable hypotheses regarding temporal changes in tongue colorimetric and microbial parameters before NEC onset. If prospectively validated, this approach may eventually contribute to a dynamic bedside monitoring tool for NEC risk stratification.
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Yang et al. (2026) studied this question.
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