Background: Increasing evidence supports a bidirectional interaction between intestinal inflammatory processes and central nervous system homeostasis along the microbiota-gut-brain axis. Disruption of the intestinal epithelial barrier facilitates the translocation of pro-inflammatory mediators, such as Interleukin-6 (IL-6), which could bypass the blood-brain barrier to trigger neuroinflammation and associated neurobehavioural comorbidities. Bergamot essential oil (BEO) is a chemically defined phytocomplex with documented neuroprotective, anxiolytic-like and spasmolytic properties. Aim: This study evaluated the effects of BEO and its principal volatile constituents on intestinal inflammation and mucosal barrier integrity in a murine model of acute colitis. Methods: Acute colitis was induced in male CD-1 mice by administering Dextran Sulphate Sodium (DSS, 4%) in drinking water for five days. Mice received daily intraperitoneal injections (250 µL/kg) of BEO, a phytochemical mixture, or linalyl acetate. Disease severity was monitored via the disease activity index. At the experimental endpoint, immunohistochemical analyses were performed on proximal and distal colon segments to assess tight junction immunoreactivity, reservoir of mucus, cytokine expression, and neuro-immune cell infiltration. Analysis used ImageJ (Fiji). Results: DSS exposure induced a robust colitic phenotype characterised by severe clinical disease activity, marked histopathological injury, epithelial barrier disruption, and enhanced mucosal inflammatory signalling. The distal colon was the most affected region, showing significant depletion of mucin-2 immunoreactivity (MUC-2 IR) and disruption of occludin-associated tight-junction organisation compared with control animals. Treatment with BEO and its constituents was associated with partial preservation of barrier integrity, evidenced by greater retention of MUC-2 IR and a more continuous junctional occludin pattern relative to DSS-treated mice. In parallel, DSS-induced increases in mucosal IL-6 expression and CD117+ mast-cell density were attenuated by the treatments. In the proximal colon, where DSS-induced injury was comparatively less severe, treated animals showed a tendency towards preservation of barrier-associated markers. Conclusions: Given the recognised role of mast cells and pro-inflammatory cytokines as key mediators of microbiota–gut–brain axis communication, these findings suggest modulation of gut-derived inflammatory signalling pathways by the phytocomplex potentially involved in neuroimmune crosstalk.
Modulating the microbiota-gut-brain axis via bergamot essential oil: a multi-target approach to mitigate systemic triggers of neuroinflammation
De Rasis Enrica;Rombola Laura;Scuteri Damiana;Corasaniti Maria Tiziana;Bagetta Giacinto;Morrone Luigi Antonio
2026-01-01
Abstract
Background: Increasing evidence supports a bidirectional interaction between intestinal inflammatory processes and central nervous system homeostasis along the microbiota-gut-brain axis. Disruption of the intestinal epithelial barrier facilitates the translocation of pro-inflammatory mediators, such as Interleukin-6 (IL-6), which could bypass the blood-brain barrier to trigger neuroinflammation and associated neurobehavioural comorbidities. Bergamot essential oil (BEO) is a chemically defined phytocomplex with documented neuroprotective, anxiolytic-like and spasmolytic properties. Aim: This study evaluated the effects of BEO and its principal volatile constituents on intestinal inflammation and mucosal barrier integrity in a murine model of acute colitis. Methods: Acute colitis was induced in male CD-1 mice by administering Dextran Sulphate Sodium (DSS, 4%) in drinking water for five days. Mice received daily intraperitoneal injections (250 µL/kg) of BEO, a phytochemical mixture, or linalyl acetate. Disease severity was monitored via the disease activity index. At the experimental endpoint, immunohistochemical analyses were performed on proximal and distal colon segments to assess tight junction immunoreactivity, reservoir of mucus, cytokine expression, and neuro-immune cell infiltration. Analysis used ImageJ (Fiji). Results: DSS exposure induced a robust colitic phenotype characterised by severe clinical disease activity, marked histopathological injury, epithelial barrier disruption, and enhanced mucosal inflammatory signalling. The distal colon was the most affected region, showing significant depletion of mucin-2 immunoreactivity (MUC-2 IR) and disruption of occludin-associated tight-junction organisation compared with control animals. Treatment with BEO and its constituents was associated with partial preservation of barrier integrity, evidenced by greater retention of MUC-2 IR and a more continuous junctional occludin pattern relative to DSS-treated mice. In parallel, DSS-induced increases in mucosal IL-6 expression and CD117+ mast-cell density were attenuated by the treatments. In the proximal colon, where DSS-induced injury was comparatively less severe, treated animals showed a tendency towards preservation of barrier-associated markers. Conclusions: Given the recognised role of mast cells and pro-inflammatory cytokines as key mediators of microbiota–gut–brain axis communication, these findings suggest modulation of gut-derived inflammatory signalling pathways by the phytocomplex potentially involved in neuroimmune crosstalk.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
