JK5G postbiotics attenuate immune-related adverse events in NSCLC patients by regulating gut microbiota: a randomized controlled trial in China

Mengting Chen; Liling Ma; Huiqing Yu; Shaoyi Huang; Junhui Zhang; Juan Gong; Liejun Yang; Lan Chen; Haojun Luo; Ling Tian; Sixiong Wang

doi:10.3389/fonc.2023.1155592

JK5G postbiotics attenuate immune-related adverse events in NSCLC patients by regulating gut microbiota: a randomized controlled trial in China

Front Oncol. 2023 Aug 4:13:1155592. doi: 10.3389/fonc.2023.1155592. eCollection 2023.

Authors

Mengting Chen¹, Liling Ma², Huiqing Yu^{1

2}, Shaoyi Huang², Junhui Zhang², Juan Gong², Liejun Yang², Lan Chen², Haojun Luo², Ling Tian², Sixiong Wang²

Affiliations

¹ Department of Clinical Nutrition, Chongqing University Cancer Hospital, School of Medicine, Chongqing University, Chongqing, China.
² Department of Geriatric Oncology and Department of Palliative Care, Chongqing University Cancer Hospital, School of Medicine, Chongqing University, Chongqing, China.

Abstract

Scope: This 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).

Methods: This 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).

Results: Sixty 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.

Conclusion: Our 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 registration: www.chictr.org.cn, identifier ChiCTR2200064690.

Keywords: enterotype; gut microbiota; immune-related adverse events; non-small-cell lung cancer; postbiotics.

Grants and funding

This research was supported by Chongqing medical scientific research project (Joint project of Chongqing Health Commission and Science and Technology Bureau) (No.2021MSXM128), Chongqing Talents Program (cstc2021ycjh-bgzxm0256), Natural Science Foundation of Chongqing, China (cstc2021jcyj-msxmX0400), Chongqing medicinal biotech association of scientific research projects(cmba2022kyym-zkxmQ0011), and Chongqing Research Institution Performance Incentive and Guidance Project (cstc2022jxjl120007).