{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T14:27:10Z","timestamp":1788532030790,"version":"build-2803163510"},"reference-count":140,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Acute brain injury, including traumatic brain injury (TBI), stroke, subarachnoid hemorrhage and secondary neurological injury, such as sepsis-associated encephalopathy (SAE) and delirium, is a major cause of morbidity in the intensive care unit (ICU), and few treatments alter its course once it is established. Critical illness, and brain injury in particular, rapidly disrupts the gut microbiome (GM) and the production of its metabolites. This dysbiosis matters most in neurologically injured patients, because microbial metabolites and a leaky intestinal barrier feed neuroinflammation through the gut\u2013brain axis. Feeding timing and fasting affect circadian biology, the daily rhythm of the GM, and host metabolic pathways, such as ketogenesis, insulin signaling and autophagy. This review asks whether time-restricted or fasting-mimicking strategies can preserve these functions and reduce neuroimmune dysregulation after brain injury. Methods: In this narrative review, we searched the literature for randomized trials, crossover pilot studies, mechanistic human research, and guideline statements comparing continuous, cyclic, and intermittent enteral strategies, and evaluated translational pathways for GM-targeted feeding interventions. Results: Available studies showed no consistent difference in mortality between continuous and intermittent gastric feeding in ICU adults on mechanical ventilation, although the largest pooled analyses report more diarrhea, more abdominal distension and longer ICU stay with intermittent schedules, most pronounced in ventilated patients. While intermittent\/cyclic regimens were not associated with an improvement of patient-centered outcomes, pilot studies demonstrated that short macronutrient interruptions (e.g., 12 h) reliably induced a metabolic fasting response in patients with a prolonged ICU stay. One randomized controlled trial (RCT) had GM end-points and reported feasible modulation of gut taxa and 58 differentially abundant serum metabolites with sequential (continuous-to-intermittent) feeding. Only five studies enrolled dedicated brain-injured cohorts; none was designed around neurological or gut\u2013brain mechanistic outcomes, and none measured GM or neuroinflammation. Conclusions: Time-restricted, microbiome-protecting approaches are biologically plausible and deserve a phased translational program to test them in clinical trials. Future trials should focus on brain-injured and other neurologically relevant ICU patients, in whom the gut\u2013brain axis is most engaged, and should pair mechanistic endpoints with clinical safety and proper control for confounders. No clinical study has yet tested whether non-continuous feeding alters neuroinflammatory or neurological outcomes after acute brain injury. There is currently no direct evidence supporting the effectiveness of this intervention in this population, and the case made here is mechanistic, not empirical.<\/jats:p>","DOI":"10.3390\/nu18172907","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T13:50:44Z","timestamp":1788529844000},"page":"2907","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Improving\u00a0the Outcome of Brain-Injured Patients by Non-Continuous Feeding to Prevent Dysbiosis"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9760-9394","authenticated-orcid":false,"given":"Alberto","family":"Corriero","sequence":"first","affiliation":[{"name":"Department of Interdisciplinary Medicine\u2014ICU Section, University of Bari Aldo Moro, 70124 Bari, Italy"},{"name":"Department of Intensive Care, Universit\u00e9 Libre de Bruxelles (ULB), 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8069-3171","authenticated-orcid":false,"given":"Rossana","family":"Soloperto","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Medicine\u2014ICU Section, University of Bari Aldo Moro, 70124 Bari, Italy"},{"name":"Department of Intensive Care, Universit\u00e9 Libre de Bruxelles (ULB), 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariateresa","family":"Giglio","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Medicine\u2014ICU Section, University of Bari Aldo Moro, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio Silvio","family":"Taccone","sequence":"additional","affiliation":[{"name":"Department of Intensive Care, Universit\u00e9 Libre de Bruxelles (ULB), 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7274-6467","authenticated-orcid":false,"given":"Filomena","family":"Puntillo","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Medicine\u2014ICU Section, University of Bari Aldo Moro, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3163-0390","authenticated-orcid":false,"given":"Jean-Charles","family":"Preiser","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Institut Jules Bordet, Universit\u00e9 Libre de Bruxelles (ULB), 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1007\/s00134-025-07967-1","article-title":"Traumatic Brain Injury Management in the Intensive Care Unit: Standard of Care and Knowledge Gaps","volume":"51","author":"Robba","year":"2025","journal-title":"Intensive Care Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1056\/NEJMoa1301372","article-title":"Long-Term Cognitive Impairment after Critical Illness","volume":"369","author":"Pandharipande","year":"2013","journal-title":"N. 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