The Impact of Gut Microbiota Diversity on Follicular Lymphoma: Insights into Disease Progression and Therapy

Introduction

Follicular lymphoma (FL) is the most common indolent B-cell lymphoma. While treatments such as chemotherapy and anti-CD20 monoclonal antibody (mAb) therapy are available, a cure remains elusive. Moreover, approximately 20% of patients experience early relapse within 24 months, which significantly increases the risk of reduced survival, with the underlying mechanisms still not fully understood. Epidemiological studies have shown that the incidence rate of FL was historically higher in Western countries compared to China. However, recent data indicates that the incidence rate in China has now reached similar levels to those in the West. It is well-known that altered dietary behavior can change the composition of gut microbiota. In this study, we analyzed fecal samples from 42 patients with follicular lymphoma and found that the gut microbiota may contribute to both the onset and progression of FL.

Results

Among 42 patients, median age was 52 (30-71), 25 (58%) were female. Within this cohort, 28 patients were diagnosed with grade 1 or 2 follicular lymphoma, while 14 patients had grade 3. Among these, 5 patients showed partial transformation to diffuse large B-cell lymphoma (DLBCL).

Microbiome diversity sequencing analysis revealed a significant alteration in microbiome diversity compared to the control group. Using Krona and Python software for a preliminary analysis, we found that 51% of individuals in the control group exhibited very high gut microbial diversity, whereas only 17% of FL patients demonstrated similar levels of diversity. Additionally, 21% of FL patients had extremely low gut microbial diversity, including 6 patients with high-grade FL. These findings suggest a strong correlation between the progression of FL and the degree of gut microbial diversity.

Phenotypic analysis of the gut microbiota revealed that the microbiota of FL patients is predominantly Gram-negative, while the control group primarily consists of Gram-positive bacteria. Additionally, the control group largely relies on biofilms to create a protective environment for bacteria, shielding them from environmental stress and maintaining a stable gut ecosystem through cooperative symbiosis. In contrast, FL patients' gut microbiota demonstrated a significantly reduced ability to form biofilms compared to the control group. This indicates that FL patients may depend on colonization by microorganisms with higher tolerance to environmental stress to maintain a stable symbiotic environment. The phenotypic analysis of environmental stress tolerance aligns with the observed decrease in gut microbial diversity in FL patients.

In-depth analysis of the gut microbiota showed a remarkable increase in the relative abundance of beneficial bacteria in FL patients, including Bacteroides and Agathobacter. Bacteroides plays a crucial role in the metabolism of polysaccharides and oligosaccharides, providing vital nutrients and vitamins to both the host and other gut microbes. Similarly, Agathobacter, which is associated with slowing tumor growth and reducing immune-related side effects, was also found in higher levels.

Conclusion

Dysbiosis of the gut microbiota in follicular lymphoma patients and an increase in potentially pathogenic bacteria, possibly related to the development of FL. Meanwhile, certain probiotics were significantly enriched in the gut of FL patients, potentially associated with the indolent progression of FL in most cases.

No relevant conflicts of interest to declare.