Altered abundance in cancer patients gut of diadenylate cyclase-encoding bacteria

Area of Science:

• Microbiome research
• Immunology
• Oncology

Background:

• Cyclic di-AMP (c-di-AMP) is a bacterial second messenger that engages host immune sensors, notably the STING pathway.
• This interaction connects gut microbiota activity to tumor immunity, presenting therapeutic potential for cancer patients.
• Emerging evidence indicates microbial c-di-AMP can bolster anti-tumor responses and enhance treatments like PD-1/PD-L1 blockade and radiotherapy.

Purpose of the Study:

• To identify gut microbial species capable of synthesizing c-di-AMP.
• To analyze the abundance of c-di-AMP-producing bacteria in healthy individuals versus cancer patients.
• To explore the relationship between c-di-AMP-producing bacteria and response to cancer immunotherapy.

Main Methods:

• Mining the Unified Human Gastrointestinal Protein catalogue for diadenylate cyclases (DACs).
• Constructing a comprehensive database of DACs across numerous microbial species.
• Analyzing metagenomic data from healthy subjects and cancer patients (melanoma, NSCLC, renal carcinoma).

Main Results:

• A database of 4,228 DACs from 3,901 species was generated.
• Species encoding DACs were significantly more abundant in healthy microbiota compared to cancer-associated microbiota.
• No significant differences in DAC-encoding species abundance were observed between immunotherapy responders and non-responders.

Conclusions:

• C-di-AMP-producing bacteria are depleted in the microbiota of cancer patients.
• These findings highlight the potential role of c-di-AMP-producing bacteria in modulating anti-tumor immunity.
• Further research is warranted to investigate the therapeutic implications of these bacteria in oncology.