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Open research questions in Clinical Nutrition and Gastroenterology

41 unresolved questions extracted from the limitations and future-work sections of 280 Clinical Nutrition and Gastroenterology papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Persistent nutritional inadequacy reflects insufficiently defined physiological requirements and limited implementable evidence-based guidance during ICU recovery.

    Individualizing post-ICU nutrition: from guideline intent to bedside practice · 2026 · DOI

  • One of the major limitations of the study was that the peptide-based formula groups were recruited from 18 centers, while the SPF control groups were derived from only two centers.

    Peptide-based versus standard polymeric enteral nutrition in the PICU: a multicenter observational study · 2026 · DOI

  • Abstract Background Nutritional therapy is a key component of critical care management, yet optimal strategies remain debated due to the heterogeneity of ICU patients, dynamic metabolic alterations, and the profound influence of inflammation on nutrient utilisation.

    Current concepts on feeding the critically ill patient: a narrative review · 2026 · DOI

  • Conclusion Current evidence is most consistent with a scenario-dependent interpretation of GT placement through the drainage channel of second-generation SGAs, rather than routine universal placement or universal avoidance; the available sample sizes were insufficient to exclude clinically important differences in rare safety outcomes.

    Gastric tube placement through the drainage channel of second-generation supraglottic airway devices: a systematic review with evidence mapping · 2026 · DOI

  • Background Second-generation supraglottic airway (SGA) devices incorporate a dedicated gastric drainage channel that permits placement of a gastric tube (GT), but whether GT placement should be used routinely during general anaesthesia remains uncertain.

    Gastric tube placement through the drainage channel of second-generation supraglottic airway devices: a systematic review with evidence mapping · 2026 · DOI

  • Clinical scenarios were grouped into three interpretive categories reflecting indirect evidence signals consistent with GT placement, no evidence supporting routine GT placement, or insufficient or context-limited evidence.

    Gastric tube placement through the drainage channel of second-generation supraglottic airway devices: a systematic review with evidence mapping · 2026 · DOI

  • 1 Strengths and limitations This study has several notable strengths, including a large multicenter sample and the integrated evaluation of clinical, nutri- tional, and gut microbiota characteristics across different levels of AGI severity.

    Retrospective analysis of intestinal flora alterations in adults with acute gastrointestinal injury · 2026 · DOI

  • Participants suggestions on ways to improve decision-making around PN fell under three main categories; information provision, including mode of delivery, the information they required to make an informed decision and ways to improve service provision (Fig 1).

    Parenteral nutrition in advanced cancer: A qualitative study on decision-making and information needs of patients and carers · 2026 · DOI

  • The paper identifies that patients with high nutritional risk (mNUTRIC ≥5) experienced increased 60-day mortality with early enteral nutrition (OR 1.52), yet no mechanistic studies have investigated whether this adverse interaction is driven by feeding-induced splanchnic ischemia, bacterial translocation, or metabolic intolerance specific to high-risk vasopressor-dependent populations.

    What is The Effect of Early Enteral Nutrition on Mortality in Critically Ill Patients Receiving Vasopressor Support? : A Systematic Review · 2026 · DOI

  • Multiple studies identified varying vasopressor dose thresholds for safe enteral nutrition initiation (≤0.14 µg/kg/min by Merchan et al., <0.3 µg/kg/min by Luping Wang et al., 0.23 µg/kg/min by Fan Qi et al.), but no prospective study has prospectively validated which norepinephrine-equivalent dose cutoff, in combination with clinical perfusion parameters, reliably predicts enteral feeding tolerance and prevents mesenteric ischemia across different patient populations.

    What is The Effect of Early Enteral Nutrition on Mortality in Critically Ill Patients Receiving Vasopressor Support? : A Systematic Review · 2026 · DOI

  • The paper documents inconsistent mortality outcomes across disease-specific cohorts (COVID-19 pneumonia showing benefits, septic shock showing variable results, ARDS and traumatic brain injury requiring tailored approaches), yet no comparative effectiveness trials have systematically evaluated organ-dysfunction-specific feeding strategies (dose, timing, route) to determine risk-benefit profiles for ARDS, acute pancreatitis, and traumatic brain injury patients on vasopressor support.

    What is The Effect of Early Enteral Nutrition on Mortality in Critically Ill Patients Receiving Vasopressor Support? : A Systematic Review · 2026 · DOI

  • While the NUTRIREA-3 trial demonstrated that low-calorie enteral nutrition (6 kcal/kg/day) halved bowel ischemia risk compared to standard-calorie feeding (25 kcal/kg/day), no randomized controlled trials have directly compared gradual advancement protocols (3-7 day escalation) versus immediate full-dose feeding in patients with persistent shock receiving high-dose vasopressors (≥0.3 µg/kg/min norepinephrine equivalents) to determine long-term outcome differences.

    What is The Effect of Early Enteral Nutrition on Mortality in Critically Ill Patients Receiving Vasopressor Support? : A Systematic Review · 2026 · DOI

  • The paper identifies a critical need to develop and validate biomarkers of gut perfusion and tolerance (such as lactate trends, base deficit measurements, and splanchnic perfusion indicators) that can guide individualized early enteral nutrition strategies in vasopressor-supported patients, but no studies have prospectively evaluated which combination of biomarkers best predicts feeding tolerance and prevents bowel ischemia.

    What is The Effect of Early Enteral Nutrition on Mortality in Critically Ill Patients Receiving Vasopressor Support? : A Systematic Review · 2026 · DOI

  • Organ-axis mechanisms in gut–brain, gut–lung, gut–kidney, gut–liver, and gut–heart crosstalk require alignment with specific, monitorable biomarkers and clinically recognizable intermediate phenotypes—for example, dynamic monitoring of intestinal fatty acid-binding protein and short-chain fatty acid-related metabolic signatures—to enable source-stratified trial design and risk stratification in sepsis-associated gastrointestinal injury.

    Source-stratified gut–extraintestinal organ crosstalk in sepsis-associated acute gastrointestinal injury and paralytic ileus: the gut as both driver and target · 2026 · DOI

  • In extraintestinal sepsis, the organ-specific pathways through which lung-, brain-, kidney-, liver-, or heart-derived insults converge on the gut to trigger secondary acute gastrointestinal injury and progression toward paralytic ileus have not been experimentally validated with source-stratified interventions targeting individual organ-to-gut axes.

    Source-stratified gut–extraintestinal organ crosstalk in sepsis-associated acute gastrointestinal injury and paralytic ileus: the gut as both driver and target · 2026 · DOI

  • In enterogenic sepsis specifically, the dominant routes through which gut-derived inflammatory, microbial, metabolic, vascular, and extracellular vesicle signals propagate toward distant organs remain uncharacterized and require systematic mapping of directional signaling pathways to distinguish primary from secondary organ injury.

    Source-stratified gut–extraintestinal organ crosstalk in sepsis-associated acute gastrointestinal injury and paralytic ileus: the gut as both driver and target · 2026 · DOI

  • The source-stratified framework for gut–organ crosstalk requires identification of axis-specific decisive nodes—including which cellular subsets, molecular mediators, and ligand–receptor interactions are both biologically central and clinically actionable—across distinct organ-to-gut pathways in lung-, brain-, kidney-, liver-, and heart-derived insults in extraintestinal sepsis.

    Source-stratified gut–extraintestinal organ crosstalk in sepsis-associated acute gastrointestinal injury and paralytic ileus: the gut as both driver and target · 2026 · DOI

  • Study limited by uncontrolled potential confounders; future studies should incorporate multivariable regression analyses to better account for confounding factors and clarify associations between gut microbiota, GLP-1, and feeding intolerance.

    GLP-1–gut microbiotal axis and enteral feeding intolerance in critically ill neurological patients · 2026 · DOI

  • Weak correlations between microbial composition and feeding intolerance, increasing risk of Type II errors (false negatives), requiring confirmation in future large-scale, multicenter cohort studies.

    GLP-1–gut microbiotal axis and enteral feeding intolerance in critically ill neurological patients · 2026 · DOI

  • Conclusion: Combining supplemental PN with enteral support improves energy intake and prognosis in gastrointestinal cancer, though limited studies restrict publication bias evaluation.

    Efficacy and Safety of a Combination of Enteral and Parenteral Nutrition Support in the Postoperative Period for Patients with Gastrointestinal Cancer: A Systematic Review and Meta-Analysis · 2025 · DOI

  • OBJECTIVE: Percutaneous endoscopic gastrostomy (PEG) has become the preferred method to provide enteral tube feeding to older adults who have difficulty eating, but the impact of PEG on patient outcomes is poorly understood.

    Outcomes of Percutaneous Endoscopic Gastrostomy Among Older Adults in a Community Setting · 2000 · DOI

  • Evidence from younger populations suggests higher-calorie refeeding (HCR) may be safe and more efficient, but adult data is limited.

    Can higher calorie feeding protocols for eating disorder patients admitted to an adult hospital ward be safely implemented to reduce the length of stay? A scoping review · 2026 · DOI

  • Background Enteral feeding tolerance during vasopressor therapy remains uncertain, particularly within the moderate-dose gray zone.

    Arterial lactate and enteral feeding intolerance within the vasopressor gray zone: a retrospective cohort study · 2026 · DOI

  • Current evidence supports the glutamate–glutamine axis as a mechanistically relevant pathway and a source of candidate biomarkers, but pediatric-specific data remain limited and do not yet justify routine biomarker use or glutamine-based intervention in unselected children with septic shock.

    The Glutamate–Glutamine Axis in Pediatric Septic Shock: Immunometabolic Mechanisms, Biomarker Potential, and Clinical Implications · 2026 · DOI

  • The temporal hierarchy of mechanisms in sepsis-associated acute gastrointestinal injury remains unclear—specifically, whether the progression from early perfusion mismatch and barrier destabilization toward later immune dysregulation, immunometabolic remodeling, extracellular vesicle-mediated communication, and regulated cell-death propagation follows a predictable sequence, and at what timepoints each mechanism becomes dominant in enterogenic versus extraintestinal sepsis contexts.

    Source-stratified gut–extraintestinal organ crosstalk in sepsis-associated acute gastrointestinal injury and paralytic ileus: the gut as both driver and target · 2026 · DOI

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41 open questions have been extracted from the limitations and future-work passages of 280 Clinical Nutrition and Gastroenterology papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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