Restoring gut microbiota after antibiotic exposure: the role of beneficial commensals in immune checkpoint inhibitor outcomes – a systematic review

Zahra Rizqika Aliyya Safitri; Tri Hariningsih

doi:10.22146/inajbcs.v57i3.Supplement.24315

Zahra Rizqika Aliyya Safitri Delima Primary Clinic, Yogyakarta, Indonesia
Tri Hariningsih Department of Internal Medicine, Dr. Suhardi Hardjolukito Air Force Central Hospital, Yogyakarta, Indonesia

DOI: https://doi.org/10.22146/inajbcs.v57i3.Supplement.24315

Keywords: Gut Microbiota, Antibiotics, Probiotics, Immune Checkpoint Inhibitors, Fecal Microbiota Transplantation

Abstract

Antibiotic-induced gut dysbiosis is one mechanism that can reduce the effective immune checkpoint inhibitor (ICI) therapy. Disruption of beneficial gut microbes may weaken antitumor immune responses, reducing the impact of immunotherapy. This systematic review explored strategies to restore gut microbiota after antibiotic exposure and their influence on clinical outcomes in patients receiving ICIs. The literature search was conducted according to the PRISMA 2020 guidelines through PubMed, Embase, Cochrane Library, and Web of Science until June 2025. A total of 1,247 records were screened, 98 full-text articles were assessed, and 5 studies met the inclusion criteria. All studies noted the use of broad-spectrum antibiotics, some combined with narrow-spectrum agents. Restoration approaches included fecal microbiota transplantation (FMT) and probiotic-based therapies, most commonly CBM588, administered before or alongside ICI treatment. These interventions were often integrated with chemotherapy or targeted therapies such as VEGFR inhibitors and platinum-based regimens. Restoration timing generally followed ICI cycles, ranging from 2 to 6 weeks. Microbiota restoration was associated with improved progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Patients receiving FMT or probiotics, particularly CBM588, showed higher rates of complete or partial response and longer median survival compared to those without intervention. Mechanistic findings revealed recovery of beneficial commensals such as Bifidobacterium and Akkermansia, increased short-chain fatty acid production, and enhanced T-cell activation markers. These results suggest that restoring gut microbial balance may help re-establish immune responsiveness and improve ICI outcomes. Although the number of eligible studies was limited and designs varied, the evidence highlights the clinical relevance of microbiota restoration in overcoming antibiotic-related resistance to ICIs. Microbiota-based strategies have the potential to become part of cancer management, although prospective trials are needed to determine the most effective timing, methods, and combinations.