JK5G postbiotics attenuate immune-related adverse events in NSCLC patients by regulating gut microbiota: a randomized controlled trial in China
ScopeThis study aimed to evaluate the effects of JK5G postbiotics to regulate imbalanced gut microbiota and its impacts on the efficacy and incidence rate of immune-related adverse events (irAEs) in non-small-cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs).MethodsT...
Main Authors: | , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2023-08-01
|
Series: | Frontiers in Oncology |
Subjects: | |
Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1155592/full |
_version_ | 1827877288639725568 |
---|---|
author | Mengting Chen Liling Ma Huiqing Yu Huiqing Yu Shaoyi Huang Junhui Zhang Juan Gong Liejun Yang Lan Chen Haojun Luo Ling Tian Sixiong Wang |
author_facet | Mengting Chen Liling Ma Huiqing Yu Huiqing Yu Shaoyi Huang Junhui Zhang Juan Gong Liejun Yang Lan Chen Haojun Luo Ling Tian Sixiong Wang |
author_sort | Mengting Chen |
collection | DOAJ |
description | ScopeThis study aimed to evaluate the effects of JK5G postbiotics to regulate imbalanced gut microbiota and its impacts on the efficacy and incidence rate of immune-related adverse events (irAEs) in non-small-cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs).MethodsThis randomized, double-blind, placebo-controlled trial was conducted in China and included non-squamous or squamous NSCLC patients without EGFR, ROS1, and ALK alteration, treatment-naive, and stage IIIb-IV. Patients were randomly (1:1) divided into two groups to receive four cycles (three weeks for each cycle) of programmed cell death-1 (PD-1) plus chemotherapy plus placebo (control group, n = 30) or to receive PD-1 plus chemotherapy plus JK5G postbiotics (JK5G group, n = 30). The primary endpoint was objective response rate. The secondary endpoints were quality of life (QoL), adverse effects, and the 16S DNA sequencing of gut microbiota, blood inflammatory cytokines, and lymphocyte subsets. This study was registered at www.chictr.org.cn (ChiCTR2200064690).ResultsSixty patients were enrolled. The objective response rate was 36.67% (11/30) in the control group and 50.00% (15/30) in the JK5G group (p = 0.297). The JK5G group had better QoL and nutritional levels, as well as lower depression symptoms than the control group (all p < 0.05). Moreover, the JK5G group had a lower incidence of anemia (63.33% vs. 13.33%, p < 0.001), decreased lymphocyte count (20.00% vs. 0%, p = 0.010), decreased appetite (53.33% vs. 16.67%, p = 0.003), nausea (33.33% vs. 6.67%, p = 0.010), and asthenia (30.00% vs. 6.67%, p = 0.017) than the control group. Moreover, JK5G attenuated gut microbiota imbalance, accompanied by increased Faecalibacterium, Ruminococcaceae, and fecal butyrate concentration, and diminished Escherichia-Shigella. Furthermore, JK5G administration significantly decreased the levels of pro-inflammatory markers, including TNF-α, IL-2, and C-reactive protein (CRP) (all p < 0.05). Significant increases in CD3+CD4+ T cells and CD4/CD8 ratio were observed in the peripheral blood of JK5G group patients (all p < 0.05). The enterotype data showed that patients were clustered into Blautia (E1) and Escherichia-Shigella (E2) enterotypes, and JK5G postbiotics intervention might be related to enterotype modulations.ConclusionOur current findings indicated that JK5G postbiotics might attenuate irAEs, and enhance the QoL and nutrition levels of advanced NSCLC patients who received ICIs. JK5G postbiotics could also improve the gut microbiota structures and ameliorate the tumor microenvironment and inflammation.Clinical trial registrationwww.chictr.org.cn, identifier ChiCTR2200064690. |
first_indexed | 2024-03-12T17:35:19Z |
format | Article |
id | doaj.art-28385e30e70648efadb813f145174111 |
institution | Directory Open Access Journal |
issn | 2234-943X |
language | English |
last_indexed | 2024-03-12T17:35:19Z |
publishDate | 2023-08-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Oncology |
spelling | doaj.art-28385e30e70648efadb813f1451741112023-08-04T11:42:39ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-08-011310.3389/fonc.2023.11555921155592JK5G postbiotics attenuate immune-related adverse events in NSCLC patients by regulating gut microbiota: a randomized controlled trial in ChinaMengting Chen0Liling Ma1Huiqing Yu2Huiqing Yu3Shaoyi Huang4Junhui Zhang5Juan Gong6Liejun Yang7Lan Chen8Haojun Luo9Ling Tian10Sixiong Wang11Department of Clinical Nutrition, Chongqing University Cancer Hospital, School of Medicine, Chongqing University, Chongqing, ChinaDepartment of Geriatric Oncology and Department of Palliative Care, Chongqing University Cancer Hospital, School of Medicine, Chongqing University, Chongqing, ChinaDepartment of Clinical Nutrition, Chongqing University Cancer Hospital, School of Medicine, Chongqing University, Chongqing, ChinaDepartment of Geriatric Oncology and Department of Palliative Care, Chongqing University Cancer Hospital, School of Medicine, Chongqing University, Chongqing, ChinaDepartment of Geriatric Oncology and Department of Palliative Care, Chongqing University Cancer Hospital, School of Medicine, Chongqing University, Chongqing, ChinaDepartment of Geriatric Oncology and Department of Palliative Care, Chongqing University Cancer Hospital, School of Medicine, Chongqing University, Chongqing, ChinaDepartment of Geriatric Oncology and Department of Palliative Care, Chongqing University Cancer Hospital, School of Medicine, Chongqing University, Chongqing, ChinaDepartment of Geriatric Oncology and Department of Palliative Care, Chongqing University Cancer Hospital, School of Medicine, Chongqing University, Chongqing, ChinaDepartment of Geriatric Oncology and Department of Palliative Care, Chongqing University Cancer Hospital, School of Medicine, Chongqing University, Chongqing, ChinaDepartment of Geriatric Oncology and Department of Palliative Care, Chongqing University Cancer Hospital, School of Medicine, Chongqing University, Chongqing, ChinaDepartment of Geriatric Oncology and Department of Palliative Care, Chongqing University Cancer Hospital, School of Medicine, Chongqing University, Chongqing, ChinaDepartment of Geriatric Oncology and Department of Palliative Care, Chongqing University Cancer Hospital, School of Medicine, Chongqing University, Chongqing, ChinaScopeThis study aimed to evaluate the effects of JK5G postbiotics to regulate imbalanced gut microbiota and its impacts on the efficacy and incidence rate of immune-related adverse events (irAEs) in non-small-cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs).MethodsThis randomized, double-blind, placebo-controlled trial was conducted in China and included non-squamous or squamous NSCLC patients without EGFR, ROS1, and ALK alteration, treatment-naive, and stage IIIb-IV. Patients were randomly (1:1) divided into two groups to receive four cycles (three weeks for each cycle) of programmed cell death-1 (PD-1) plus chemotherapy plus placebo (control group, n = 30) or to receive PD-1 plus chemotherapy plus JK5G postbiotics (JK5G group, n = 30). The primary endpoint was objective response rate. The secondary endpoints were quality of life (QoL), adverse effects, and the 16S DNA sequencing of gut microbiota, blood inflammatory cytokines, and lymphocyte subsets. This study was registered at www.chictr.org.cn (ChiCTR2200064690).ResultsSixty patients were enrolled. The objective response rate was 36.67% (11/30) in the control group and 50.00% (15/30) in the JK5G group (p = 0.297). The JK5G group had better QoL and nutritional levels, as well as lower depression symptoms than the control group (all p < 0.05). Moreover, the JK5G group had a lower incidence of anemia (63.33% vs. 13.33%, p < 0.001), decreased lymphocyte count (20.00% vs. 0%, p = 0.010), decreased appetite (53.33% vs. 16.67%, p = 0.003), nausea (33.33% vs. 6.67%, p = 0.010), and asthenia (30.00% vs. 6.67%, p = 0.017) than the control group. Moreover, JK5G attenuated gut microbiota imbalance, accompanied by increased Faecalibacterium, Ruminococcaceae, and fecal butyrate concentration, and diminished Escherichia-Shigella. Furthermore, JK5G administration significantly decreased the levels of pro-inflammatory markers, including TNF-α, IL-2, and C-reactive protein (CRP) (all p < 0.05). Significant increases in CD3+CD4+ T cells and CD4/CD8 ratio were observed in the peripheral blood of JK5G group patients (all p < 0.05). The enterotype data showed that patients were clustered into Blautia (E1) and Escherichia-Shigella (E2) enterotypes, and JK5G postbiotics intervention might be related to enterotype modulations.ConclusionOur current findings indicated that JK5G postbiotics might attenuate irAEs, and enhance the QoL and nutrition levels of advanced NSCLC patients who received ICIs. JK5G postbiotics could also improve the gut microbiota structures and ameliorate the tumor microenvironment and inflammation.Clinical trial registrationwww.chictr.org.cn, identifier ChiCTR2200064690.https://www.frontiersin.org/articles/10.3389/fonc.2023.1155592/fullpostbioticsgut microbiotaimmune-related adverse eventsnon-small-cell lung cancerenterotype |
spellingShingle | Mengting Chen Liling Ma Huiqing Yu Huiqing Yu Shaoyi Huang Junhui Zhang Juan Gong Liejun Yang Lan Chen Haojun Luo Ling Tian Sixiong Wang JK5G postbiotics attenuate immune-related adverse events in NSCLC patients by regulating gut microbiota: a randomized controlled trial in China Frontiers in Oncology postbiotics gut microbiota immune-related adverse events non-small-cell lung cancer enterotype |
title | JK5G postbiotics attenuate immune-related adverse events in NSCLC patients by regulating gut microbiota: a randomized controlled trial in China |
title_full | JK5G postbiotics attenuate immune-related adverse events in NSCLC patients by regulating gut microbiota: a randomized controlled trial in China |
title_fullStr | JK5G postbiotics attenuate immune-related adverse events in NSCLC patients by regulating gut microbiota: a randomized controlled trial in China |
title_full_unstemmed | JK5G postbiotics attenuate immune-related adverse events in NSCLC patients by regulating gut microbiota: a randomized controlled trial in China |
title_short | JK5G postbiotics attenuate immune-related adverse events in NSCLC patients by regulating gut microbiota: a randomized controlled trial in China |
title_sort | jk5g postbiotics attenuate immune related adverse events in nsclc patients by regulating gut microbiota a randomized controlled trial in china |
topic | postbiotics gut microbiota immune-related adverse events non-small-cell lung cancer enterotype |
url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1155592/full |
work_keys_str_mv | AT mengtingchen jk5gpostbioticsattenuateimmunerelatedadverseeventsinnsclcpatientsbyregulatinggutmicrobiotaarandomizedcontrolledtrialinchina AT lilingma jk5gpostbioticsattenuateimmunerelatedadverseeventsinnsclcpatientsbyregulatinggutmicrobiotaarandomizedcontrolledtrialinchina AT huiqingyu jk5gpostbioticsattenuateimmunerelatedadverseeventsinnsclcpatientsbyregulatinggutmicrobiotaarandomizedcontrolledtrialinchina AT huiqingyu jk5gpostbioticsattenuateimmunerelatedadverseeventsinnsclcpatientsbyregulatinggutmicrobiotaarandomizedcontrolledtrialinchina AT shaoyihuang jk5gpostbioticsattenuateimmunerelatedadverseeventsinnsclcpatientsbyregulatinggutmicrobiotaarandomizedcontrolledtrialinchina AT junhuizhang jk5gpostbioticsattenuateimmunerelatedadverseeventsinnsclcpatientsbyregulatinggutmicrobiotaarandomizedcontrolledtrialinchina AT juangong jk5gpostbioticsattenuateimmunerelatedadverseeventsinnsclcpatientsbyregulatinggutmicrobiotaarandomizedcontrolledtrialinchina AT liejunyang jk5gpostbioticsattenuateimmunerelatedadverseeventsinnsclcpatientsbyregulatinggutmicrobiotaarandomizedcontrolledtrialinchina AT lanchen jk5gpostbioticsattenuateimmunerelatedadverseeventsinnsclcpatientsbyregulatinggutmicrobiotaarandomizedcontrolledtrialinchina AT haojunluo jk5gpostbioticsattenuateimmunerelatedadverseeventsinnsclcpatientsbyregulatinggutmicrobiotaarandomizedcontrolledtrialinchina AT lingtian jk5gpostbioticsattenuateimmunerelatedadverseeventsinnsclcpatientsbyregulatinggutmicrobiotaarandomizedcontrolledtrialinchina AT sixiongwang jk5gpostbioticsattenuateimmunerelatedadverseeventsinnsclcpatientsbyregulatinggutmicrobiotaarandomizedcontrolledtrialinchina |