Research Summary

Adjunctive Psychobiotics Improve Pain in Gastrointestinal Cancer

Miranda Manier, BA

Key Highlights

  • In a post hoc analysis of the randomized, placebo-controlled ProDeCa trial, adjunctive psychobiotics reduced pain in gastrointestinal (GI) cancer patients on chemotherapy, with the largest benefit in non-depressed participants.
  • Improvements spanned multiple measures and were sustained up to 2 months after the 1-month intervention.
  • Placebo groups showed worsening pain over time, likely reflecting ongoing chemotherapy and disease progression; analgesic benefit with psychobiotics was smaller but still observable in participants who were depressed.

In a post hoc analysis of the randomized, placebo-controlled ProDeCa study, adjunctive psychobiotics produced clinically meaningful and sustained reductions in pain among postoperative gastrointestinal (GI) oncology patients undergoing chemotherapy. Benefits were most pronounced in participants who were not depressed and were observed across quantitative (Visual Analog Scale [VAS]) and qualitative (Short-Form McGill Pain Questionnaire [SF-MPQ] sensory and affective subscales, Present Pain Intensity [PPI]) indices, supporting psychobiotics as a promising non-opioid add-on to multimodal cancer pain management.

Pain in GI cancer is multifactorial, driven by tumor biology, surgical trauma, and chemotherapy-related toxicities, and often persists despite guideline-based analgesia. Psychobiotics, probiotic strains with neuroactive properties, may modulate pain via anti-inflammatory, neuroimmune, and gut–brain axis mechanisms. Evidence for their analgesic role in oncology has been limited, prompting this targeted analysis.

Participants in ProDeCa were adults post–GI tumor resection commencing chemotherapy (primarily FOLFOX or FOLFIRI) and receiving standard analgesia per the WHO three-step ladder. For the present analysis, cohorts were stratified by depression status using the 17-item Hamilton Depression Rating Scale (HDRS-D-17): non-depressed (HDRS-D-17 ≤ 7; n = 167: psychobiotics 84, placebo 83) and depressed (n = 99: psychobiotics 48, placebo 51). The intervention comprised a four-strain psychobiotic formulation (Bifidobacterium animalis subsp. lactis BS01, B. breve BR03, B. longum BL04, and Lacticaseibacillus rhamnosus GG; total daily dose 1.76 × 10¹¹ CFU) administered twice daily for 4 weeks. Pain was assessed at baseline (T0), end of treatment (T1, 1 month), and follow-up (T2, 3 months) using the SF-MPQ (total Pain Rating Index and its sensory [11 items] and affective [4 items] components), VAS (0–100), and PPI (0–5).

Among participants who were not depressed receiving psychobiotics, VAS pain decreased significantly from T0 to T1 (P = .002) and continued to decline from T1 to T2 (P = .001), indicating persistence of benefit 2 months post-intervention. In contrast, placebo recipients who were not depressed showed a progressive increase in VAS pain (T0–T2, P = .008). PPI decreased significantly in psychobiotic groups (non-depressed and depressed) and increased in both placebo groups. For the SF-MPQ, psychobiotics reduced the total Pain Rating Index over time in participants who were not depressed, with significant declines in both sensory (P = .04) and affective (P < .001) subscales; depressed psychobiotic recipients showed the same direction of effect without statistical significance. Placebo groups (regardless of mood status) exhibited rising sensory (non-depressed P < .001; depressed P = .03) and affective (depressed P = .025; trend in non-depressed) indices over time. Notably, baseline analyses indicated that participants who were not depressed reported higher pain intensity and broader pain descriptors than participants who were depressed, yet experienced larger pain reductions with psychobiotics.

Limitations include the post hoc design; reliance on patient-reported pain measures; heterogeneity of chemotherapy regimens; absence of microbiome profiling to link mechanism with response; and small subgroups (e.g., participants whose depression status improved). These factors may limit generalizability and preclude causal inference specific to mood strata.

“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," Tzikos and colleagues concluded. “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.”

Reference
Tzikos G, Menni AE, Theodorou H, et al. Beyond analgesia: psychobiotics as an adjunctive approach to pain management in gastrointestinal oncology-a post hoc analysis from the ProDeCa study. Nutrients. 2025;17(17):2751. doi:10.3390/nu17172751Top of Form