Beyond Analgesia: Psychobiotics as an Adjunctive Approach to Pain Management in Gastrointestinal Oncology—A Post Hoc Analysis from the ProDeCa Study

Background: Pain is a multifaceted and debilitating symptom in patients with gastrointestinal cancer, especially those undergoing surgical resection followed by chemotherapy. The interplay between inflammatory, neuropathic, and psychosocial components often renders conventional analgesia insufficient. Psychobiotics—probiotic strains with neuroactive properties—have recently emerged as potential modulators of pain perception through neuroimmune and gut–brain axis pathways. Methods: This post hoc analysis is based on the ProDeCa randomized, placebo-controlled trial, which originally aimed to assess the psychotropic effects of a four-strain psychobiotic formulation in postoperative gastrointestinal cancer patients receiving chemotherapy. In the current analysis, we evaluated changes in pain perception among non-depressed and depressed participants, who received either psychobiotics or placebo, along with standard analgesic regimes. Pain was assessed at baseline, after a month of treatment, and at follow-up, 2 months thereafter, using the Short-Form McGill Pain Questionnaire (SF-MPQ), capturing both sensory and affective components, as well as with the Present Pain Intensity and the VAS scores. Results: Psychobiotic-treated participants—particularly the non-depressed ones—exhibited a significant reduction in both quantitative and qualitative pain indices over time compared with placebo-treated ones. Improvements were noted in total pain rating index scores, sensory and affective subscales, and present pain intensity. These effects were sustained up to 2 months after intervention. In contrast, placebo groups demonstrated worsening in pain scores, probably influenced by ongoing chemotherapy and disease progression. The analgesic effect was less pronounced but still observable in the subgroup with symptoms of depression. Conclusions: Adjunctive psychobiotic therapy appears to beneficially modulate pain perception in gastrointestinal oncology patients receiving chemotherapy, with the most pronounced effects being in non-depressed individuals. These findings suggest psychobiotics as a promising non-opioid add-on for comprehensive cancer pain management and support further investigation in larger pain-targeted trials.