Oral microbial signatures : from severe infections to immune responses

This thesis investigates the diversity of oral microbial signatures, and the profound clinical and immunological significance they have in human pathologies, from localized infections to systemic immunological interactions.

Study 1 was an 11-year epidemiological analysis of severe oral infections in Stockholm County. Characterization of 1,014 samples using MALDI-TOF mass spectrometry revealed highly dynamic microbial populations associated with different oral infections. Streptococcus spp., Prevotella spp., and Staphylococcus spp. predominated, while the evolving populations of Streptococcus anginosus and Actinomyces spp. had potential systemic implications.

Study 2 was a 6-year retrospective analysis exploring the mycobiota profiles of head and neck cancer (HNC) patients with oral fungal infections (OFIs) and undergoing radiotherapy. Candida albicans was the most prevalent pathogen, co-occurring with emerging populations of non-albicans Candida (NAC) species and novel isolates, including Fusarium solani and Candida jadinii. Network analyses revealed significant multispecies co-occurrence, particularly during radiotherapy, underscoring the need for tailored antifungal strategies in this vulnerable population.

Study 3 evaluated the oral microbiome's influence on coronavirus disease 2019 (COVID-19) vaccine immunogenicity in 115 participants, including healthy controls and people living with HIV (PLHIV). Comparative analyses revealed distinct microbial profiles in high- and low-responders. Gram-negative anaerobes, such as Campylobacter and Prevotella, predominated in low- responders, and Gram-positive saccharolytic species in high-responders, implicating the distribution of oral microbial populations in modulating mucosal immunity and possibly in long-term vaccine outcomes.

Study 4 focused on MAIT cell responses to bacterial secretomes derived from blood, oral, and pancreatic tumor isolates. Activation patterns were strongly influenced by bacterial origin, irrespective of species, with tumor-derived strains inducing unique polyfunctional cytokine profiles. This highlights the pivotal role of microbial metabolites in shaping immune responses, offering novel insights into host-microbe interactions in oral infections and cancer.

Collectively, this work advances our understanding of oral microbial signatures in health and disease, revealing their critical role in shaping systemic immunity and providing a foundation for microbiome-targeted therapeutic interventions.

List of scientific papers

I. Al-Manei K, Ghorbani M, Naud S, Al-Manei KK, Sobkowiak MJ, Lund B, Hazirolan G, Sällberg Chen M,, Özenci V. Clinical microbial identification of severe oral infections by MALDI-TOF mass spectrometry in Stockholm County: an 11-Year (2010 to 2020) epidemiological investigation. Microbiology Spectrum. 2022 Dec 21;10(6):e02487-22.
https://doi.org/10.1128/spectrum.02487-22

II. Al-Manei K, Sobkowiak MJ, Nagadia RH, Heymann R, Sällberg Chen M, Özenci V. Mycobiota profile of oral fungal infections in head and neck cancer patients receiving radiotherapy: A 6- year retrospective MALDI-TOF mass spectrometry study. Oral Oncology. 2023 Nov 1;146:106556.
https://doi.org/10.1016/j.oraloncology.2023.106556

III. Ghorbani M*, Al-Manei K*, Naud S, Healy K, Gabarrini G, Sobkowiak MJ, Chen P, Ray S, Akber M, Muschiol S, Bogdanovic G, Bergman P, Ljungman P, Buggert M, Ljunggren HG, Pin E, Nowak P, Aleman S, Sällberg Chen M. Persistence of salivary antibody responses after COVID-19 vaccination is associated with oral microbiome variation in both healthy and people living with HIV. Frontiers in Immunology. 2023 Jan 10;13:1079995.
https://doi.org/10.3389/fimmu.2022.1079995

IV. Al-Manei K, Unalan-Altintop T, Johnsson A, Santini R, Khan ZA, Halimi A, Özenci V, Sällberg Chen M, Sobkowiak MJ. MAIT cell polyfunctional response to bacterial secretome is dependent on site of microbial origin. 2025. [Manuscript]

*Contributed equally