Assessing the impact of probiotics on immunotherapy effectiveness and antibiotic-mediated resistance in cancer: a systematic review and meta-analysis

BackgroundProbiotics have been demonstrated to exert a potential clinical enhancing effect in cancer patients receiving immune checkpoint inhibitors (ICIs), while antibiotics exert a detrimental impact. Prior meta-analysis papers have substantial limitations and are devoid of recent published studie...

Full description

Saved in:
Bibliographic Details
Main Authors: Shuya Zhao, Zian Lu, Fangmin Zhao, Shihuan Tang, Lishan Zhang, Cuiling Feng
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1538969/full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849344470842081280
author Shuya Zhao
Shuya Zhao
Zian Lu
Fangmin Zhao
Shihuan Tang
Lishan Zhang
Cuiling Feng
author_facet Shuya Zhao
Shuya Zhao
Zian Lu
Fangmin Zhao
Shihuan Tang
Lishan Zhang
Cuiling Feng
author_sort Shuya Zhao
collection DOAJ
description BackgroundProbiotics have been demonstrated to exert a potential clinical enhancing effect in cancer patients receiving immune checkpoint inhibitors (ICIs), while antibiotics exert a detrimental impact. Prior meta-analysis papers have substantial limitations and are devoid of recent published studies. Therefore, this study aimed to perform an updated meta-analysis and, for the first time, assess whether probiotics can restore the damage of antibiotics to immunotherapy.MethodsA comprehensive literature search was conducted in three English databases and three Chinese databases with a cutoff date of August 11, 2024. The methodological quality of the studies was evaluated using the Newcastle-Ottawa Quality Assessment Scale (NOS) or the Revised Cochrane risk-of-bias tool (RoB 2). Engauge Digitizer v12.1 was employed to extract hazard ratios (HRs) with 95% confidence interval (CI) for survival outcomes when these data were not explicitly provided in the manuscripts. Meta-analysis was conducted using Stata 14 software.ResultsThe study sample comprised eight retrospective and four prospective studies, involving a total of 3,142 participants. The findings indicate that probiotics significantly prolong the overall survival (OS) (I2 = 31.2%; HR=0.58, 95% CI: 0.46-0.73, p < 0.001) and progression-free survival (PFS) (I2 = 65.2%; HR=0.66, 95% CI: 0.54-0.81, p < 0.001) in cancer patients receiving ICIs, enhance the objective response rate (ORR) (I2 = 33.5%; OR=1.75, 95% CI: 1.27-2.40, p = 0.001) and disease control rate (DCR) (I2 = 50.0%; OR=1.93, 95% CI: 1.11-3.35, p = 0.002). For non-small cell lung cancer (NSCLC) patients exposed to antibiotics, the use of probiotics was associated with superior OS (I2 = 0.0%; HR=0.45, 95% CI: 0.34-0.59, p < 0.001) and PFS (I2 = 0.0%; HR=0.48, 95% CI: 0.38-0.62, p < 0.001) when compared to non-users. Subgroup differences were observed regarding the cancer type (P=0.006) and ethnic backgrounds (P=0.011) in OS.ConclusionsThe meta-analysis findings suggest that probiotics can effectively extend the survival of cancer treated with ICIs. In NSCLC, probiotics appear to mitigate the negative impact of antibiotics on immunotherapy effectiveness, which has profound clinical significance. Nevertheless, additional large-scale, high-quality randomized controlled trials are necessary to further validate these findings.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=579047, identifier CRD42024579047.
format Article
id doaj-art-0da4f6caef904f708595211caaa26cb9
institution Kabale University
issn 1664-3224
language English
publishDate 2025-03-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Immunology
spelling doaj-art-0da4f6caef904f708595211caaa26cb92025-08-20T03:42:40ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-03-011610.3389/fimmu.2025.15389691538969Assessing the impact of probiotics on immunotherapy effectiveness and antibiotic-mediated resistance in cancer: a systematic review and meta-analysisShuya Zhao0Shuya Zhao1Zian Lu2Fangmin Zhao3Shihuan Tang4Lishan Zhang5Cuiling Feng6Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, ChinaPeking University People’s Hospital, Beijing, ChinaDongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, ChinaDepartment of First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Beijing, ChinaDongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, ChinaPeking University People’s Hospital, Beijing, ChinaBackgroundProbiotics have been demonstrated to exert a potential clinical enhancing effect in cancer patients receiving immune checkpoint inhibitors (ICIs), while antibiotics exert a detrimental impact. Prior meta-analysis papers have substantial limitations and are devoid of recent published studies. Therefore, this study aimed to perform an updated meta-analysis and, for the first time, assess whether probiotics can restore the damage of antibiotics to immunotherapy.MethodsA comprehensive literature search was conducted in three English databases and three Chinese databases with a cutoff date of August 11, 2024. The methodological quality of the studies was evaluated using the Newcastle-Ottawa Quality Assessment Scale (NOS) or the Revised Cochrane risk-of-bias tool (RoB 2). Engauge Digitizer v12.1 was employed to extract hazard ratios (HRs) with 95% confidence interval (CI) for survival outcomes when these data were not explicitly provided in the manuscripts. Meta-analysis was conducted using Stata 14 software.ResultsThe study sample comprised eight retrospective and four prospective studies, involving a total of 3,142 participants. The findings indicate that probiotics significantly prolong the overall survival (OS) (I2 = 31.2%; HR=0.58, 95% CI: 0.46-0.73, p < 0.001) and progression-free survival (PFS) (I2 = 65.2%; HR=0.66, 95% CI: 0.54-0.81, p < 0.001) in cancer patients receiving ICIs, enhance the objective response rate (ORR) (I2 = 33.5%; OR=1.75, 95% CI: 1.27-2.40, p = 0.001) and disease control rate (DCR) (I2 = 50.0%; OR=1.93, 95% CI: 1.11-3.35, p = 0.002). For non-small cell lung cancer (NSCLC) patients exposed to antibiotics, the use of probiotics was associated with superior OS (I2 = 0.0%; HR=0.45, 95% CI: 0.34-0.59, p < 0.001) and PFS (I2 = 0.0%; HR=0.48, 95% CI: 0.38-0.62, p < 0.001) when compared to non-users. Subgroup differences were observed regarding the cancer type (P=0.006) and ethnic backgrounds (P=0.011) in OS.ConclusionsThe meta-analysis findings suggest that probiotics can effectively extend the survival of cancer treated with ICIs. In NSCLC, probiotics appear to mitigate the negative impact of antibiotics on immunotherapy effectiveness, which has profound clinical significance. Nevertheless, additional large-scale, high-quality randomized controlled trials are necessary to further validate these findings.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=579047, identifier CRD42024579047.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1538969/fullcancerimmunotherapyprobioticsantibioticsmeta-analysissystematic review
spellingShingle Shuya Zhao
Shuya Zhao
Zian Lu
Fangmin Zhao
Shihuan Tang
Lishan Zhang
Cuiling Feng
Assessing the impact of probiotics on immunotherapy effectiveness and antibiotic-mediated resistance in cancer: a systematic review and meta-analysis
Frontiers in Immunology
cancer
immunotherapy
probiotics
antibiotics
meta-analysis
systematic review
title Assessing the impact of probiotics on immunotherapy effectiveness and antibiotic-mediated resistance in cancer: a systematic review and meta-analysis
title_full Assessing the impact of probiotics on immunotherapy effectiveness and antibiotic-mediated resistance in cancer: a systematic review and meta-analysis
title_fullStr Assessing the impact of probiotics on immunotherapy effectiveness and antibiotic-mediated resistance in cancer: a systematic review and meta-analysis
title_full_unstemmed Assessing the impact of probiotics on immunotherapy effectiveness and antibiotic-mediated resistance in cancer: a systematic review and meta-analysis
title_short Assessing the impact of probiotics on immunotherapy effectiveness and antibiotic-mediated resistance in cancer: a systematic review and meta-analysis
title_sort assessing the impact of probiotics on immunotherapy effectiveness and antibiotic mediated resistance in cancer a systematic review and meta analysis
topic cancer
immunotherapy
probiotics
antibiotics
meta-analysis
systematic review
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1538969/full
work_keys_str_mv AT shuyazhao assessingtheimpactofprobioticsonimmunotherapyeffectivenessandantibioticmediatedresistanceincancerasystematicreviewandmetaanalysis
AT shuyazhao assessingtheimpactofprobioticsonimmunotherapyeffectivenessandantibioticmediatedresistanceincancerasystematicreviewandmetaanalysis
AT zianlu assessingtheimpactofprobioticsonimmunotherapyeffectivenessandantibioticmediatedresistanceincancerasystematicreviewandmetaanalysis
AT fangminzhao assessingtheimpactofprobioticsonimmunotherapyeffectivenessandantibioticmediatedresistanceincancerasystematicreviewandmetaanalysis
AT shihuantang assessingtheimpactofprobioticsonimmunotherapyeffectivenessandantibioticmediatedresistanceincancerasystematicreviewandmetaanalysis
AT lishanzhang assessingtheimpactofprobioticsonimmunotherapyeffectivenessandantibioticmediatedresistanceincancerasystematicreviewandmetaanalysis
AT cuilingfeng assessingtheimpactofprobioticsonimmunotherapyeffectivenessandantibioticmediatedresistanceincancerasystematicreviewandmetaanalysis