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

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...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Journal of Advanced Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S2090123224000900
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author 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
author_facet 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
author_sort Surbhi Mishra
collection DOAJ
description 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.
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spelling doaj-art-81ca574820cb4a488a192f812010aa9b2025-01-18T05:04:22ZengElsevierJournal of Advanced Research2090-12322025-02-0168375386Gut microbiome-derived bacterial extracellular vesicles in patients with solid tumoursSurbhi Mishra0Mysore Vishakantegowda Tejesvi1Jenni Hekkala2Jenni Turunen3Niyati Kandikanti4Anna Kaisanlahti5Marko Suokas6Sirpa Leppä7Pia Vihinen8Hanne Kuitunen9Kaisa Sunela10Jussi Koivunen11Arja Jukkola12Ilja Kalashnikov13Päivi Auvinen14Okko-Sakari Kääriäinen15T. Peñate Medina16O. Peñate Medina17Juha Saarnio18Sanna Meriläinen19Tero Rautio20Raila Aro21Reetta Häivälä22Juho Suojanen23Mikael Laine24Pande Putu Erawijattari25Leo Lahti26Peeter Karihtala27Terhi S. Ruuska28Justus Reunanen29Research Unit of Translational Medicine, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, Finland; Corresponding author at: Biocenter Oulu, University of Oulu Aapistie 5, P.O. Box 5281, 90014 Oulu, Finland.Biocenter Oulu, University of Oulu, Oulu, Finland; Ecology and Genetics, Faculty of Science, University of Oulu, Oulu, FinlandResearch Unit of Translational Medicine, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, FinlandResearch Unit of Translational Medicine, University of Oulu, Oulu, Finland; Research Unit of Clinical Medicine, University of Oulu, Oulu, FinlandFaculty of Medicine and Health Technology, University of Tampere, Tampere, FinlandResearch Unit of Translational Medicine, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, FinlandBiocenter Oulu, University of Oulu, Oulu, FinlandDepartment of Oncology, Helsinki University Hospital Comprehensive Cancer Center, University of Helsinki, Helsinki, FinlandFICAN West Cancer Centre and Department of Oncology, Turku University Hospital and University of Turku, 20521 Turku, FinlandDepartment of Oncology, Oulu University Hospital, Oulu, FinlandFinnish Medicines Agency, Tampere, FinlandDepartment of Medical Oncology and Radiotherapy and Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, FinlandTampere Cancer Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, FinlandDepartment 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, FinlandCancer Center, Kuopio University Hospital, Northern Savonia Healthcare Municipality, Kuopio, FinlandCancer Center, Kuopio University Hospital, Northern Savonia Healthcare Municipality, Kuopio, FinlandSection Biomedical Imaging, Department of Radiology and Neuroradiology and Institute for Experimental Cancer Research, Kiel University, 24105 Kiel, GermanySection 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 NetherlandsTranslational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, Oulu, FinlandTranslational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, Oulu, FinlandTranslational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, Oulu, FinlandTranslational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, Oulu, FinlandTranslational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, Oulu, FinlandPäijät-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, FinlandDepartment of Abdominal Surgery, Porvoo Hospital, Hospital District of Helsinki and Uusimaa, Porvoo, FinlandDepartment of Computing, University of Turku, Turku, FinlandDepartment of Computing, University of Turku, Turku, FinlandDepartment of Oncology, Helsinki University Hospital Comprehensive Cancer Center, University of Helsinki, Helsinki, Finland; Department of Oncology, Oulu University Hospital, Oulu, FinlandBiocenter 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, FinlandResearch Unit of Translational Medicine, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, FinlandIntroduction: 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.http://www.sciencedirect.com/science/article/pii/S2090123224000900Bacterial extracellular vesiclesGut microbiotaCancer16S rRNA gene sequencingMachine learningProteome
spellingShingle 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
Gut microbiome-derived bacterial extracellular vesicles in patients with solid tumours
Journal of Advanced Research
Bacterial extracellular vesicles
Gut microbiota
Cancer
16S rRNA gene sequencing
Machine learning
Proteome
title Gut microbiome-derived bacterial extracellular vesicles in patients with solid tumours
title_full Gut microbiome-derived bacterial extracellular vesicles in patients with solid tumours
title_fullStr Gut microbiome-derived bacterial extracellular vesicles in patients with solid tumours
title_full_unstemmed Gut microbiome-derived bacterial extracellular vesicles in patients with solid tumours
title_short Gut microbiome-derived bacterial extracellular vesicles in patients with solid tumours
title_sort gut microbiome derived bacterial extracellular vesicles in patients with solid tumours
topic Bacterial extracellular vesicles
Gut microbiota
Cancer
16S rRNA gene sequencing
Machine learning
Proteome
url http://www.sciencedirect.com/science/article/pii/S2090123224000900
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