Adjunctive Probiotic Lactobacillus rhamnosus Probio-M9 Administration Enhances the Effect of Anti-PD-1 Antitumor Therapy via Restoring Antibiotic-Disrupted Gut Microbiota
Open accessAbstract
Emerging evidence supports that the efficacy of immune checkpoint blockade (ICB) therapy is associated with the host’s gut microbiota, as prior antibiotic intake often leads to poor outcome and low responsiveness toward ICB treatment. Therefore, we hypothesized that the efficacy of ICB therapy like anti-programmed cell death protein-1 (PD-1) treatment required an intact host gut microbiota, and it was established that probiotics could enhance the recovery of gut microbiota disruption by external stimuli. Thus, the present study aimed to evaluate the effect of the probiotics, Lactobacillus rhamnosus Probio-M9, on recovering antibiotic-disrupted gut microbiota and its impact on the outcome of ICB therapy in tumor-bearing mice. We first disrupted the mouse microbiota by antibiotics and then remediated the gut microbiota by probiotics or naturally. Tumor transplantation was then performed, followed by anti-PD-1-based antitumor therapy. Changes in the fecal metagenomes and the tumor suppression effect were monitored during different stages of the experiment. Our results showed that Probio-M9 synergized with ICB therapy, significantly improving tumor inhibition compared with groups not receiving the probiotic treatment ( P < 0.05 at most time points). The synergistic effect was accompanied by effective restoration of antibiotic-disrupted fecal microbiome that was characterized by a drastically reduced Shannon diversity value and shifted composition of dominating taxa. Moreover, probiotic administration significantly increased the relative abundance of beneficial bacteria (e.g., Bifidobacterium pseudolongum , Parabacteroides distasonis , and some Bacteroides species; 0.0001 < P < 0.05). The gut microbiome changes were accompanied by mild reshaping of the functional metagenomes characterized by enrichment in sugar degradation and vitamin and amino acid synthesis pathways. Collectively, this study supported that probiotic administration could enhance the efficacy and responsiveness of anti-PD-1-based immunotherapy, and Probio-M9 could be a potential candidate of microbe-based synergistic tumor therapeutics. The preclinical data obtained here would support the design of future human clinical trials for further consolidating the current findings and for safety assessment of probiotic adjunctive treatment in ICB therapy.
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F. prausnitzii or Lactobacillus rhamnosus restored ICB responses in the context of antibiotic-induced microbiota perturbation.
“Other probiotics like F. prausnitzii (Bredon et al., 2024) or Lactobacillus rhamnosus (Gao et al., 2021) restored ICB responses in the context of antibiotic-induced microbiota perturbation.”
From Microbiota-centered interventions to boost immune checkpoint blockade therapies (2025) · cites this paper as Gao et al., 2021
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- [8]Almonte AA Rangarajan H Yip D Fahrer AM. How Does the Gut Microbiome Influence Immune Checkpoint Blockade Therapy? Immunol Cell Biol (2020) 99(4): 361–72. doi: 10.1111/imcb.12423 33147357 · DOI · Paper page
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Microbiota-centered interventions to boost immune checkpoint blockade therapies
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- Authors
- Gao, G., Ma, T., Zhang, T., Jin, H., Li, Y., Kwok, L.-Y., Zhang, H., & Sun, Z.
- Affiliations
- Inner Mongolia Agricultural University (CN)
- Corresponding author
- Zhang, Heping
- Sun, Zhihong
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2021-12-14
- Volume
- 12
- Pages
- 772532-772532
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC8712698
- OpenAlex
- W4200535906
- Cited by
- 111
- References
- 44
- Citations by year
- 2026: 17 · 2025: 28 · 2024: 25 · 2023: 28 · 2022: 13
- FWCI
- 9.85
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Agriculture Research System of China (31720103911, 2021ZD0014)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- probiotics, anti-PD-1 therapy, immune checkpoint blockade, gut microbiota, antibiotic-induced dysbiosis, microbiota restoration, cancer immunotherapy, tumor-bearing mice, fecal microbiota, metagenome, Bifidobacterium pseudolongum, Parabacteroides distasonis, Bacteroides, tumor suppression
- MeSH terms
- Gastrointestinal Microbiome, Immune Checkpoint Inhibitors, Animals, Anti-Bacterial Agents, Bacteroides, Bifidobacterium, Feces, Mice, Inbred BALB C, Neoplasms, Probiotics, Cell Line, Tumor, Mice, Lacticaseibacillus rhamnosus, Programmed Cell Death 1 Receptor
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