Gut microbiome-derived bacterial extracellular vesicles in patients with solid tumours

Surbhi Mishra; Mysore Vishakantegowda Tejesvi; Jenni Hekkala; Jenni Turunen; Niyati Kandikanti; Anna Kaisanlahti; Marko Suokas; Sirpa Leppä; Pia Vihinen; Hanne Kuitunen; Kaisa Sunela; Jussi Koivunen; Arja Jukkola; Ilja Kalashnikov; Päivi Auvinen; Okko-Sakari Kääriäinen; T Peñate Medina; O Peñate Medina; Juha Saarnio; Sanna Meriläinen; Tero Rautio; Raila Aro; Reetta Häivälä; Juho Suojanen; Mikael Laine; Pande Putu Erawijattari; Leo Lahti; Peeter Karihtala; Terhi S Ruuska; Justus Reunanen

doi:10.1016/j.jare.2024.03.003

Gut microbiome-derived bacterial extracellular vesicles in patients with solid tumours

J Adv Res. 2024 Mar 7:S2090-1232(24)00090-0. doi: 10.1016/j.jare.2024.03.003. Online ahead of print.

Authors

Surbhi Mishra¹, Mysore Vishakantegowda Tejesvi², Jenni Hekkala³, Jenni Turunen⁴, Niyati Kandikanti⁵, Anna Kaisanlahti³, Marko Suokas⁶, Sirpa Leppä⁷, Pia Vihinen⁸, Hanne Kuitunen⁹, Kaisa Sunela¹⁰, Jussi Koivunen¹¹, Arja Jukkola¹², Ilja Kalashnikov¹³, Päivi Auvinen¹⁴, Okko-Sakari Kääriäinen¹⁴, T Peñate Medina¹⁵, O Peñate Medina¹⁶, Juha Saarnio¹⁷, Sanna Meriläinen¹⁷, Tero Rautio¹⁷, Raila Aro¹⁷, Reetta Häivälä¹⁷, Juho Suojanen¹⁸, Mikael Laine¹⁹, Pande Putu Erawijattari²⁰, Leo Lahti²⁰, Peeter Karihtala²¹, Terhi S Ruuska²², Justus Reunanen³

Affiliations

¹ Research Unit of Translational Medicine, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, Finland. Electronic address: surbhi.mishra@oulu.fi.
² Biocenter Oulu, University of Oulu, Oulu, Finland; Ecology and Genetics, Faculty of Science, University of Oulu, Oulu, Finland.
³ Research Unit of Translational Medicine, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, Finland.
⁴ Research Unit of Translational Medicine, University of Oulu, Oulu, Finland; Research Unit of Clinical Medicine, University of Oulu, Oulu, Finland.
⁵ Faculty of Medicine and Health Technology, University of Tampere, Tampere, Finland.
⁶ Biocenter Oulu, University of Oulu, Oulu, Finland.
⁷ Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center, University of Helsinki, Helsinki, Finland.
⁸ FICAN West Cancer Centre and Department of Oncology, Turku University Hospital and University of Turku, 20521 Turku, Finland.
⁹ Department of Oncology, Oulu University Hospital, Oulu, Finland.
¹⁰ Finnish Medicines Agency, Tampere, Finland.
¹¹ Department of Medical Oncology and Radiotherapy and Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland.
¹² Tampere Cancer Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
¹³ Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center, University of Helsinki, Helsinki, Finland; Research Program Unit, Applied Tumor Genomics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
¹⁴ Cancer Center, Kuopio University Hospital, Northern Savonia Healthcare Municipality, Kuopio, Finland.
¹⁵ Section Biomedical Imaging, Department of Radiology and Neuroradiology and Institute for Experimental Cancer Research, Kiel University, 24105 Kiel, Germany.
¹⁶ Section Biomedical Imaging, Department of Radiology and Neuroradiology and Institute for Experimental Cancer Research, Kiel University, 24105 Kiel, Germany; Lonza Netherlands B.V., 6167 RB Geleen, the Netherlands.
¹⁷ Translational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, Oulu, Finland.
¹⁸ Päijät-Häme Joint Authority for Health and Wellbeing, Department of Oral and Maxillofacial Surgery, Lahti Central Hospital, 15850 Lahti, Finland; Cleft Palate and Craniofacial Centre, Department of Plastic Surgery, Helsinki University Hospital, 00029 Helsinki, Finland; Clinicum, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland.
¹⁹ Department of Abdominal Surgery, Porvoo Hospital, Hospital District of Helsinki and Uusimaa, Porvoo, Finland.
²⁰ Department of Computing, University of Turku, Turku, Finland.
²¹ Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center, University of Helsinki, Helsinki, Finland; Department of Oncology, Oulu University Hospital, Oulu, Finland.
²² Biocenter Oulu, University of Oulu, Oulu, Finland; Research Unit of Clinical Medicine, University of Oulu, Oulu, Finland; Department of Pediatrics and Adolescent Medicine, Oulu University Hospital, Oulu, Finland.

PMID: 38458256
DOI: 10.1016/j.jare.2024.03.003

Abstract

Introduction: Gut microbiome-derived nanoparticles, known as bacterial extracellular vesicles (bEVs), have garnered interest as promising tools for studying the link between the gut microbiome and human health. The diverse composition of bEVs, including their proteins, mRNAs, metabolites, and lipids, makes them useful for investigating diseases such as cancer. However, conventional approaches for studying gut microbiome composition alone may not be accurate in deciphering host-gut microbiome communication. In clinical microbiome research, there is a gap in the knowledge on the role of bEVs in solid tumor patients.

Objectives: Analyzing the functionality of bEVs using (meta)genomics and proteomics could highlight the unique aspects of host-gut microbiome interactions in solid tumor patients. Therefore, we performed a comparative analysis of the proteome and microbiota composition of gut microbiome-derived bEVs isolated from patients with solid tumors and healthy controls.

Methods: After isolating bEVs from the feces of solid tumor patients and healthy controls, we performed spectrometry analysis of their proteomes and next-generation sequencing (NGS) of the 16S gene. We also investigated the gut microbiomes of feces from patients and controls using 16S sequencing and used machine learning to classify the samples into patients and controls based on their bEVs and fecal microbiomes.

Results: Solid tumor patients showed decreased microbiota richness and diversity in both the bEVs and feces. However, the bEV proteomes were more diverse in patients than in the controls and were enriched with proteins associated with the metabolism of amino acids and carbohydrates, nucleotide binding, and oxidoreductase activity. Metadata classification of samples was more accurate using fecal bEVs (100%) compared with fecal samples (93%).

Conclusion: Our findings suggest that bEVs are unique functional entities. There is a need to explore bEVs together with conventional gut microbiome analysis in functional cancer research to decipher the potential of bEVs as cancer diagnostic or therapeutic biomarkers.

Keywords: 16S rRNA gene sequencing; Bacterial extracellular vesicles; Cancer; Gut microbiota; Machine learning; Proteome.