Low Commercial Probiotic Use and a High Fiber Diet Improves Immunotherapy Response

The gut microbiome modulates response to immune checkpoint blockade (ICB), but how dietary fiber intake and commercial probiotics affect this interaction is unclear. To address this, Spencer, McQuade, Gopalakrishnan, McCulloch, Vetizou, Cogdill, and colleagues profiled the fecal microbiome of patients with melanoma and assessed ICB response. Ruminococcaceae was significantly more abundant in patients responding to anti-programmed death 1 (anti–PD-1) or other systemic therapies compared to nonresponders; however, overall gut microbiome composition was not found to be significantly different between the groups. Investigation into any reported use of commercially available probiotics in this patient cohort indicated no significant difference in progression-free survival (PFS) in those taking probiotic supplements. However, in contrast to patients taking commercial probiotics, patients treated with ICB who had a high fiber intake at or above 20 g/day did demonstrate alterations to PFS such that for every 5 g increase in daily fiber intake, a 30% lower risk of cancer progression or death was observed. To confirm these findings in preclinical models, germ-free mice received a fecal microbiota transplant from a complete responder patient and were subsequently challenged with melanoma and treated with anti–PD-L1 therapy. Mice from this cohort that were also given commercial probiotics demonstrated significantly impaired antitumor response and larger tumors as well as a significant reduction in the number of activated and interferon-γ⁺, CD8⁺ T cells, suggesting an impaired T-cell immune response. In mice receiving anti–PD-1 treatment, a high-fiber diet led to more delayed tumor growth and significantly higher T-cell activation compared with a low-fiber diet. In line with the preclinical findings, ICB-treated patients who reported sufficient fiber intake and did not take probiotics have significantly longer PFS than any other group. Overall, this study supports that improving dietary fiber intake could improve outcomes in patients on ICB, but use of commercially available probiotics could have unintended effects, suggesting dietary habits and supplement use should be carefully considered and monitored in patients. ■

Spencer CN, McQuade JL, Gopalakrishnan V, McCulloch JA, Vetizou M, Cogdill AP, et al. Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response. Science 2021;374:1632–40.

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