Role of gut microbiota and immune response in breast cancer progression

Sep 23, 2026

Uploaded by Kurz

Breast cancer remains a major cause of cancer-related death, and emerging evidence links gut microbiota to tumor development through immune-mediated mechanisms, though causality and mediation by immune cells are unclear. This Mendelian randomization (MR) study used summary statistics from genome-wide association studies of gut microbiota, immune cell traits, and breast cancer subtypes. Two-sample MR, Bayesian weighted MR, and sensitivity/pleiotropy analyses were applied, with reverse MR testing reverse causality and mediation analysis assessing immune-cell mediation. Fifteen microbiota/metabolic pathways associated with breast cancer, and DP (CD4+ CD8+)% leukocytes mediated a portion of the gut microbiota–breast cancer pathway.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Introduction

Methods

Mendelian randomization analyses

Robustness and reverse causality checks

Mediation analysis

Results and implications

RESEARCH ARTICLE Role of gut microbiota and immune response in breast cancer progression Xiaofang Zhang 1, Na Ma 2, Conghui Jin 3, and Xiaoli Cao 4 ∗ Breast cancer is one of the most prevalent cancers among women and is associated with high mortality rates. Emerging evidence suggests a link between gut microbiota and the development of various tumors, particularly those involving immune-mediated mechanisms. However, the potential relationship between gut microbiota and breast cancer—and whether this relationship is mediated by immune cells—remains unclear. This Mendelian randomization (MR) study utilized summary statistics from genome-wide association studies of 412 gut microbiota, 731 immune cell traits, and breast cancer (including its subtypes). Two-sample MR analyses were conducted to assess potential causal relationships between gut microbiota and breast cancer. To further validate the findings, Bayesian weighted MR was applied. Robustness was ensured through sensitivity, specificity, and pleiotropy analyses. A reverse MR analysis was also performed to assess the potential for reverse causality. Finally, mediation analysis was employed to investigate whether immune cells mediate the pathway from gut microbiota to breast cancer. The MR analysis identified 15 gut microbiota and related metabolic pathways significantly associated with breast cancer, with nine showing positive associations and six showing negative associations. The reverse MR analysis did not support a causal effect of breast cancer on gut microbiota. Mediation analysis revealed that DP (CD4+ CD8+ ) % leukocyte mediated the pathway between gut microbiota (PWY-6263: superpathway of menaquinol-8 biosynthesis II) and breast cancer. These findings suggest a causal relationship between gut microbiota and breast cancer, with a small portion of this effect mediated by immune cells. This study underscores the potential role of gut microbiota and immune modulation in the pathogenesis of breast cancer. Keywords: Gut microbiota, immune cells, breast cancer, Mendelian randomization, MR, causal inference. Introduction Breast cancer is one of the most commonly diagnosed cancers in women and ranks as the second leading cause of cancer-related death among women [1, 2] . Approximately one in eight women in the United States will be diagnosed with breast cancer during their lifetime [3] . The risk of developing breast cancer increases with age, rising by about 0.5% per year [4] . Previous studies [5] have suggested that the high incidence of breast cancer in some developed countries may be associated with both lifestyle and genetic factors, such as BRCA1 and BRCA2 mutations [6], as well as diet and obesity [7] . Treatment for breast cancer typically involves a combination of surgery, chemotherapy, radiotherapy, targeted therapy, and endocrine therapy. Although signiﬁcant progress has been made in early detection and treatment, options for advanced breast cancer remain limited and are often associated with a high incidence of adverse side eﬀects [8] . Despite ongoing advancements, the exact mechanisms underlying breast cancer development are still not fully understood. Therefore, further research is needed to better understand the causes of breast cancer and develop eﬀective prevention strategies. The gut microbiota, which establishes itself in the human gastrointestinal tract from birth, evolves in tandem with the host’s growth and development. It exists in a symbiotic relationship with the host and plays a critical role in maintaining overall health. The gut microbiota and the host form a complex ecosystem whereina healthy gut environment promotes the growth of beneﬁcial microbes and prevents the colonization of harmful bacteria. Additionally, the gut microbiota regulates both local and systemic immune functions. Through long-term co-evolution, the microbial ﬂora and its host have developed a close symbiotic relationship based on mutual adaptation and selection.

FAQs

What was the main research question of the study?

The study tested whether gut microbiota has a causal relationship with breast cancer progression and whether immune cells mediate that pathway.

How did the researchers assess causality between gut microbiota and breast cancer?

They used Mendelian randomization with summary statistics, including two-sample MR and Bayesian weighted MR.

What did the mediation analysis show about immune cells?

DP (CD4+ CD8+)% leukocytes mediated part of the pathway linking gut microbiota (PWY-6263: superpathway of menaquinol-8 biosynthesis II) to breast cancer.

Sep 23, 2026

Uploaded by Kurz