The effect of gastrointestinal microbiome supplementation on immune checkpoint inhibitor immunotherapy: a systematic review

Abstract

Purpose Gastrointestinal (GI) microbiome modulators, such as fecal microbiome transplants (FMTs), are being considered as supplements to standard immune checkpoint inhibitor (ICI) treatment to improve efficacy. This systematic review aims to assess the study design and outcomes of clinical trials that use FMTs to enhance ICI treatment. Methods Systematic literature searches were conducted on PubMed and Embase using search terms that included names of ICIs and gastrointestinal microbiome. A first search identified interventional trials, and the second search identified interventional, retrospective, and observational studies. Results The search for interventional trials produced 205 articles, 3 of which met the inclusion criteria. All studies had sample sizes ranging between 10 and 30 participants. 2 of the studies were single-arm studies with no control arm. One study reported an overall response rate (ORR) of 3 out of 15 (20%), a median progression-free survival (PFS) of 3 months, and a median overall survival (OS) of 7 months. The second study reported 1 complete response out of 10 (10%) and 2 partial responses out of 10 (20%). The third study reported an ORR of 58% vs. 20%, a median PFS of 12.7 months vs. 2.5 months in patients receiving nivolumab–ipilimumab plus CBM588 compared with patients receiving nivolumab–ipilimumab alone respectively, and an undefined median OS. Conclusion Current studies on the microbiome modulators with ICI use are limited in study design. Future clinical trials should be randomized, use larger sample sizes, and use an appropriate control arm to better ascertain the clinical effect of the GI microbiome on ICI treatment.

Integrative Oncology Approaches to Supporting Immune Checkpoint Inhibitor Treatment of Solid Tumours

“…The main current IO approaches in ICI support outlined in Fig. 1 include a Mediterranean-style diet with over 20 g of fibre [12 ••, 50••], regular exercise [14], the use of live biotherapeutics [82][83][84], ensuring vitamin D repletion [13,97], and minimising PPI and antibiotic use [67,[74][75][76], with many other integrative oncology approaches under study. This area is ripe for further research, ranging from dietary intervention and dietary component studies, e.g.…”

“…A pan-tumour neoadjuvant window study of a LBT, MRx0518, demonstrated long-term safety and clear evidence of immune modulation with significant anticancer efficacy [ 82 ]. In another example, Clostridium butyricum MIYAIRI 588 strain (CBM588) has demonstrated significant improvement in ORR and median PFS as a combination therapy in patients receiving nivolumab-ipilimumab and may buffer detrimental impact of PPIs in NSCLC patients receiving ICI therapy [ 83 , 84 ]. LBTs have significant immune-modulatory effects through metabolites, such as short-chain fatty acids, enhancing response to ICIs clinically [ 85 , 86 ].…”

Recent updates on the role of the gut-liver axis in the pathogenesis of NAFLD/NASH, HCC, and beyond

“…Antibodies against the immunosuppressive molecule PD-1 and its ligand PD-L1, as well as CLTA4, have been used as ICIs to activate antitumor effects. Recently, some gut bacteria have been shown to enhance the efficacy of ICIs 97 …”