Exploring the interplay between antiretroviral therapy and the gut-oral microbiome axis in people living with HIV.

The gut and oral microbiome is altered in people living with HIV (PLWH). While antiretroviral treatment (ART) is pivotal in restoring immune function in PLWH, several studies have identified an association between specific antiretrovirals, particularly integrase inhibitors (INSTI), and weight gain. In our study, we explored the differences in the oral and gut microbiota of PLWH under different ART regimens, and its correlation to Body Mass Index (BMI). Fecal and salivary samples were collected from PLWH (n = 69) and healthy controls (HC, n = 80). We performed taxonomy analysis to determine the microbial composition and relationship between microbial abundance and ART regimens, BMI, CD4+T-cell count, CD4/CD8 ratio, and ART duration. PLWH showed significantly lower richness compared to HC in both the oral and gut environment. The gut microbiome composition of INSTI-treated individuals was enriched with Faecalibacterium and Bifidobacterium, whereas non-nucleotide reverse transcriptase inhibitor (NNRTI)-treated individuals were enriched with Gordonibacter, Megasphaera, and Staphylococcus. In the oral microenvironment, Veillonella was significantly more abundant in INSTI-treated individuals and Fusobacterium and Alloprevotella in the NNRTI-treated individuals. Furthermore, Bifidobacterium and Dorea were enriched in gut milieu of PLWH with high BMI. Collectively, our findings identify distinct microbial profiles, which are associated with different ART regimens and BMI in PLWH on successful ART, thereby highlighting significant effects of specific antiretrovirals on the microbiome.

Distinct oral DNA viral signatures in rheumatoid arthritis: a Pilot study.

Background: Despite evidence linking viruses and oral microbiome to rheumatoid arthritis (RA), limited whole genome sequencing research has been conducted on the oral virome (a viral component of the microbiome) of untreated RA patients. This pilot research seeks to address this knowledge gap by comparing the oral virome of untreated rheumatoid arthritis patients (RAs) and healthy individuals (HCs). Method: Whole genome DNA sequence of saliva samples from 45 participants including 21 RAs and 24 age and gender matched HCs was obtained from the BioProject: PRJEB6997. Metaphlan3 pipeline and LEfSe analysis were used for the viral signature detection. Wilcoxon pairwise test and ROC analysis were used to validate and predict signatures. Results: RA exhibits higher alpha diversity compared to HCs. Callitrichine gammaherpesvirus 3, Human gammaherpesvirus 4 (EBV), Murid betaherpesvirus 8, and Suid alphaherpesvirus 1 were enriched in RAs, while Aotine betaherpesvirus 1 from the Cytomegalovirus genus was enriched in HCs. In addition, Saccharomyces cerevisiae killer virus M1 (ScV-M1) was found to be enriched in RAs, whereas bacteriophage Hk97virus (Siphoviridae) and Cd119virus (Myoviridae) were enriched in HCs. Conclusion: This study identifies significant DNA oral viral signatures at species level as potential biomarkers for the early detection and diagnosis of rheumatoid arthritis.

A metagenomic study of gut viral markers in amyloid-positive Alzheimer's disease patients.

BACKGROUND: Mounting evidence suggests the involvement of viruses in the development and treatment of Alzheimer's disease (AD). However, there remains a significant research gap in metagenomic studies investigating the gut virome of AD patients, leaving gut viral dysbiosis in AD unexplored. This study aimed to fill this gap by conducting a metagenomics analysis of the gut virome in both amyloid-positive AD patients (Aß + ADs) and healthy controls (HCs), with the objective of identifying viral signatures linked with AD. METHOD: Whole-genome sequence (WGS) data from 65 human participants, including 30 Aß + ADs and 35 HCs, was obtained from the database NCBI SRA (Bio Project: PRJEB47976). The Metaphlan3 pipeline and linear discriminant analysis effect size (LEfSe) analysis were utilized for the bioinformatics process and the detection of viral signatures, respectively. In addition, the Benjamini-Hochberg method was applied with a significance cutoff of 0.05 to evaluate the false discovery rate for all biomarkers identified by LEfSe. The CombiROC model was employed to determine the discriminatory power of the viral signatures identified by LEfSe. RESULTS: Compared to HCs, the gut virome profiles of Aß + ADs showed lower alpha diversity, indicating a lower bacteriophage richness. The Siphoviridae family was decreased in Aß + ADs. Significant decreases of Lactococcus phages were found in Aß + ADs, including bIL285, Lactococcus phage bIL286, Lactococcus phage bIL309, and Lactococcus phage BK5 T, Lactococcus phage BM13, Lactococcus phage P335 sensu lato, Lactococcus phage phiLC3, Lactococcus phage r1t, Lactococcus phage Tuc2009, Lactococcus phage ul36, and Lactococcus virus bIL67. The predictive combined model of these viral signatures obtained an area under the curve of 0.958 when discriminating Aß + ADs from HCs. CONCLUSION: This is the first study to identify distinct viral signatures in the intestine that can be used to effectively distinguish individuals with AD from HCs.

Unveiling the Human Brain Virome in Brodmann Area 46: Novel Insights Into Dysbiosis and Its Association With Schizophrenia.

Research suggests a potential role of the oral-neuro and gut-brain axes in schizophrenia, involving non-brain microbiomes such as salivary and gut microbiomes. However, the blood-brain barrier effectively prevents microorganism entry. Additionally, despite approximately 8% of the human genome consisting of retroviruses and the established link between viral infections and schizophrenia, the presence of a resident virome (a viral component of the microbiome) in the brain and its association with mental disorders remain unexplored. METHODS: Whole-genome sequencing raw data from postmortem Brodmann Area 46 (BA46) tissue from 49 individuals (20 healthy controls [HCs], 29 with schizophrenia [SCZs]) obtained from the NCBI SRA database from BioProject: PRJNA422380.Virome profiles were retrieved using Metaphlan3, and viral signatures were identified using linear discriminant analysis effect size (LEfSe). Mann-Whitney tests and receiver operating characteristic curve validated the viral signatures. RESULTS: In BA46, 30 distinct species representing 9 phyla, 10 classes, 10 orders, 13 families, and 19 genera were identified. HCs exhibited greater alpha diversity, and there were significant differences in beta diversity between the groups. LEfSe analysis highlighted distinct viral levels, including Escherichia virus Lambda, Escherichia virus phiV10, Human endogenous retrovirus K, Taterapox virus, Alcelaphine gammaherpesvirus 1, and Bovine gammaherpesvirus 4 in HCs, while Glypta fumiferanae ichnovirus and unknown virus showed higher levels in schizophrenia. CONCLUSION: This is the first study to identify a human brain virome associated with schizophrenia in BA46. Brain virome dysbiosis may be associated with mental illness, and viral signatures may serve as biomarkers for the early detection of schizophrenia.

Clinical Microbial Identification of Severe Oral Infections by MALDI-TOF Mass Spectrometry in Stockholm County: an 11-Year (2010 to 2020) Epidemiological Investigation.

Growing evidence suggests that oral infections can modify the course of systemic diseases. To date, epidemiological data on microbial oral infections are scarce. Here, we performed a comprehensive analysis of the trend and microbial diversity in oral infection specimens referred for clinical microbiology analysis from 2010 to 2020. The microbes were isolated by culture and were identified via matrix-assisted laser desorption ionization-time of flight mass spectrometry technology (MALDI-TOF MS) throughout the study period. A total of 1,014 referred samples from dental clinics in Stockholm County with dentoalveolar abscesses and jaw osteomyelitis being the main reason were identified. Overall, the microbial composition was dominated by Firmicutes (51%), followed by Bacteroidetes (19%), Proteobacteria (12%), and Actinobacteria (5%). At the genus level, Streptococcus spp. (36%), Prevotella spp. (18%), and Staphylococcus spp. (11%) were among the most frequently reported. Interestingly, a strong increase in trend was noted for Streptococcus anginosus, Streptococcus mitis, Streptococcus sanguinis, Eikenella corrodens, Actinomyces spp., Aggregatibacter aphrophilus, Staphylococcus epidermidis, and Granulicatella adiacens during the study time (R = 0.66 to 0.89, P < 0.05), and a minor increase was noted for Enterococcus faecalis and Klebsiella spp., whereas steady levels were noted for most of the others. The present study shows the diversity of bacteria that have been involved in dental infections during the last decade in the capital of Sweden, as well as the emerging oral microbiota trend, with clear clinical implications on the oral-systemic link. IMPORTANCE Oral diseases and associated microbes are a risk factor for systemic diseases and can change the courses of these diseases. To date, epidemiological data on microbial oral infections are scarce, and longitudinal reports are lacking. We present for the first time the microbial composition of severe oral bacterial infections determined via the MALDI-TOF mass spectrometry technique in a comprehensive study between 2010 and 2020 (11 years) in Stockholm County. The trend and microbial diversity of oral infections were analyzed on referred clinical microbiological samples and were processed by standardized protocols. Trend increase was noted for Streptococcus anginosus, Streptococcus mitis, Streptococcus sanguinis, Eikenella corrodens, Actinomyces spp., Aggregatibacter aphrophilus, Staphylococcus epidermidis, Granulicatella adiacens, Enterococcus faecalis, and Klebsiella spp. Our results provide new insights into the diversity and trend of oral microbiota that were involved in serious oral infections over the past decade in the capital of Sweden and may influence the oral-systemic link.

Persistence of salivary antibody responses after COVID-19 vaccination is associated with oral microbiome variation in both healthy and people living with HIV.

Coevolution of microbiome and immunity at mucosal sites is essential for our health. Whether the oral microbiome, the second largest community after the gut, contributes to the immunogenicity of COVID-19 vaccines is not known. We investigated the baseline oral microbiome in individuals in the COVAXID clinical trial receiving the BNT162b2 mRNA vaccine. Participants (n=115) included healthy controls (HC; n=57) and people living with HIV (PLHIV; n=58) who met the study selection criteria. Vaccine-induced Spike antibodies in saliva and serum from 0 to 6 months were assessed and comparative analyses were performed against the individual salivary 16S ASV microbiome diversity. High- versus low vaccine responders were assessed on general, immunological, and oral microbiome features. Our analyses identified oral microbiome features enriched in high- vs. low-responders among healthy and PLHIV participants. In low-responders, an enrichment of Gram-negative, anaerobic species with proteolytic activity were found including Campylobacter, Butyrivibrio, Selenomonas, Lachnoanaerobaculum, Leptotrichia, Megasphaera, Prevotella and Stomatobaculum. In high-responders, enriched species were mainly Gram-positive and saccharolytic facultative anaerobes: Abiotrophia, Corynebacterium, Gemella, Granulicatella, Rothia, and Haemophilus. Combining identified microbial features in a classifier using the area under the receiver operating characteristic curve (ROC AUC) yielded scores of 0.879 (healthy controls) to 0.82 (PLHIV), supporting the oral microbiome contribution in the long-term vaccination outcome. The present study is the first to suggest that the oral microbiome has an impact on the durability of mucosal immunity after Covid-19 vaccination. Microbiome-targeted interventions to enhance long-term duration of mucosal vaccine immunity may be exploited.

Understanding the role of gut microbiota in the pathogenesis of schizophrenia.

Schizophrenia is a chronic mental disorder with marked symptoms of hallucination, delusion, and impaired cognitive behaviors. Although multidimensional factors have been associated with the development of schizophrenia, the principal cause of the disorder remains debatable. Microbiome involvement in the etiology of schizophrenia has been widely researched due to the advancement in sequencing technologies. This review describes the contribution of the gut microbiome in the development of schizophrenia that is facilitated by the gut-brain axis. The gut microbiota is connected to the gut-brain axis via several pathways and mechanisms, that are discussed in this review. The role of the oral microbiota, probiotics and prebiotics in shaping the gut microbiota are also highlighted. Lastly, future perspectives for microbiome research in schizophrenia are addressed.