Predictive biomarkers for anti-TNF alpha therapy in IBD patients.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal condition characterized by severe gut inflammation, commonly presenting as Crohn's disease, ulcerative colitis or categorized as IBD- unclassified. While various treatments have demonstrated efficacy in adult IBD patients, the advent of anti-TNF therapies has significantly revolutionized treatment outcomes and clinical management. These therapies have played a pivotal role in achieving clinical and endoscopic remission, promoting mucosal healing, averting disease progression, and diminishing the necessity for surgery. Nevertheless, not all patients exhibit positive responses to these therapies, and some may experience a loss of responsiveness over time. This review aims to present a comprehensive examination of predictive biomarkers for monitoring the therapeutic response to anti-TNF therapy in IBD patients. It will explore their limitations and clinical utilities, paving the way for a more personalized and effective therapeutic approach.

Salivary microbiome and hypertension in the Qatari population.

BACKGROUND: The prevalence of hypertension in Qatar is 33 percent of the adult population. It is postulated that the salivary microbiome can regulate blood pressure (BP). However, limited investigations exist to prove this hypothesis. Therefore, we examined the difference in the salivary microbiome composition between hypertensive and normotensive Qatari subjects. METHODS: A total of 1190 Qatar Genome Project (QGP) participants (Mean age = 43 years) were included in this study. BP for all participants was classified into Normal (n = 357), Stage1 (n = 336), and Stage2: (n = 161) according to the American Heart Association guidelines. 16S-rRNA libraries were sequenced and analyzed using QIIME-pipeline, and PICRUST was used to predict functional metabolic routes. Machine Learning (ML) strategies were applied to identify salivary microbiome-based predictors of hypertension. RESULTS: Differential abundant analysis (DAA) revealed that Bacteroides and Atopobium were the significant members of the hypertensive groups. Alpha and beta diversity indices indicated dysbiosis between the normotensive and hypertensive groups. ML-based prediction models revealed that these markers could predict hypertension with an AUC (Area under the curve) of 0.89. Functional predictive analysis disclosed that Cysteine and Methionine metabolism and the sulphur metabolic pathways involving the renin-angiotensin system were significantly higher in the normotensive group. Therefore, members of Bacteroides and Atopobium can serve as predictors of hypertension. Likewise, Prevotella, Neisseria, and Haemophilus can be the protectors that regulate BP via nitric acid synthesis and regulation of the renin-angiotensin system. CONCLUSION: It is one of the first studies to assess salivary microbiome and hypertension as disease models in a large cohort of the Qatari population. Further research is needed to confirm these findings and validate the mechanisms involved.

An integrated tumor, immune and microbiome atlas of colon cancer.

The lack of multi-omics cancer datasets with extensive follow-up information hinders the identification of accurate biomarkers of clinical outcome. In this cohort study, we performed comprehensive genomic analyses on fresh-frozen samples from 348 patients affected by primary colon cancer, encompassing RNA, whole-exome, deep T cell receptor and 16S bacterial rRNA gene sequencing on tumor and matched healthy colon tissue, complemented with tumor whole-genome sequencing for further microbiome characterization. A type 1 helper T cell, cytotoxic, gene expression signature, called Immunologic Constant of Rejection, captured the presence of clonally expanded, tumor-enriched T cell clones and outperformed conventional prognostic molecular biomarkers, such as the consensus molecular subtype and the microsatellite instability classifications. Quantification of genetic immunoediting, defined as a lower number of neoantigens than expected, further refined its prognostic value. We identified a microbiome signature, driven by Ruminococcus bromii, associated with a favorable outcome. By combining microbiome signature and Immunologic Constant of Rejection, we developed and validated a composite score (mICRoScore), which identifies a group of patients with excellent survival probability. The publicly available multi-omics dataset provides a resource for better understanding colon cancer biology that could facilitate the discovery of personalized therapeutic approaches.

Modulation of gut microbiota: The effects of a fruits and vegetables supplement.

The consumption of an optimal amount of fruits and vegetables is known to improve physical fitness and physiological body functions. Healthy eating habits, including intake of fruits and vegetables, can modify gut microbiota. This study aimed to demonstrate the effectiveness of a formulated fruit and vegetable supplement (FVS) in modulating the antioxidant capacity and the gut microbiota composition. We enrolled 30 healthy volunteer subjects, matched for age, gender, BMI, and smoking habits, and randomized them into the FVS and the placebo (PLA) groups. Among the serum vitamins, the folic acid level was significantly higher (p = 0.001) in the FVS group than in the PLA group, whereas the vitamin B2 level was significantly higher in the PLA group than in the FVS group (p = 0.028). The antioxidant capacity, measured by using the oxygen radical absorbance capacity (ORAC) method, was also slightly higher in the FVS group than in the PLA group but did not reach statistical significance. The dietary intake, assessed by 24-h recalls, did not show any significant changes after the supplementation in both the groups. The gut microbiome composition, measured by 16S rDNA sequencing, showed no difference in both alpha and beta diversities, whereas the LEfse analysis revealed a microbial shift after the treatment, with a decreased abundance of the genus Ruminococcus from the Lachnospiraceae family (p = 0.009), and the unclassified genus from the family Erysipelotrichaceae (UC36, p = 0.003) in the FVS group compared with the PLA group (confirmed by SIAMCAT analysis, AUC = 74.1%). With a minor effect, the genus Faecalibacterium and unclassified genus and family from the order Lactobacillales (UC31) were also increased in the FVS group compared with the PLA group (p = 0.0474, p = 0.0352, respectively). SCFA measurement by gas chromatography-mass spectrometry showed an increased level of 2-methylbutyrate in the FVS group compared with the PLA group (p = 0.0385). Finally, the Spearman correlation analysis showed that in the FVS group, the genus Faecalibacterium positively correlated with 2-methyl butyrate (p = 0.040). In the PLA group, none of the significant bacteria correlated with either SCFA or serum biomarkers. The network analysis confirmed the positive correlation between genus Faecalibacterium and 2-methyl butyrate. We can conclude that the FVS in healthy individuals modified the gut microbiota composition and metabolites, and it can potentially contribute to reduce the pro-inflammatory response along with the antioxidant capacity.

The Salivary miRNome: A Promising Biomarker of Disease.

MicroRNAs (miRNAs) are non-coding RNAs ranging from 18-24 nucleotides, also known to regulate the human genome mainly at the post-transcriptional level. MiRNAs were shown to play an important role in most biological processes such as apoptosis and in the pathogenesis of many diseases such as cardiovascular diseases and cancer. Recent developments of advanced molecular high-throughput technologies have enhanced our knowledge of miRNAs. MiRNAs can now be discovered, interrogated, and quantified in various body fluids serving as diagnostic and therapeutic markers for many diseases. While most studies use blood as a sample source to measure circulating miRNAs as possible biomarkers for disease pathogenesis, fewer studies have assessed the role of salivary miRNAs in health and disease. This review aims at providing an overview of the current knowledge of the salivary miRNome, addressing the technical aspects of saliva sampling, and highlighting the applicability of miRNA screening to clinical practice.

The vaginal and fecal microbiota of a murine cervical carcinoma model under synergistic effect of 17ß-Estradiol and E7 oncogene expression.

Cervical cancer is an important health issue worldwide. Many factors are related to this condition as the persistence of human papillomavirus (HPV) infection (e.g. type 16 and 18), the use of hormonal contraceptives for long periods of time, pH changes and bacterial vaginosis. The association between the microbiota and cervical human cancer is an interesting issue to be explored; given that environmental and hormonal factors may change the vaginal microbiota contributing to this condition. Our hypothesis was that changes in the microbiota diversity is associated with the development of cervical cancer. We evaluated the microbiota diversity in vaginal lavages and fecal samples at different stages of cervical cancer development in a mice model (K14HPV16E7) with type 16 E7 oncogene expression (E7), under continuous or not continuous stimulus of 17ß-estradiol (E2) and compared it with a non-transgenic isogenic control (FVB) under same conditions. Our results indicate that continuous E2 administration during 6 months in the model with type 16 E7 expression causing development of cancer, is associated with significant changes in the microbiota diversity of the cervicovaginal lavages. Similar results were not observed in the same model when no E2 was administered to the mice. The FVB mice with no E7 expression which do not develop cervical cancer, did not show comparable changes in the microbiota diversity when E2 was administered during the same period. Normal evolution of the cervical epithelium and microbiota diversity were observed for the FVB mice with no E2 administration. Large changes in the microbiota diversity in fecal samples were not observed suggesting a specific organ effect of E7 expression associated to E2 on the vaginal microbiota.

Annexin A3 in sepsis: novel perspectives from an exploration of public transcriptome data.

According to publicly available transcriptome datasets, the abundance of Annexin A3 (ANXA3) is robustly increased during the course of sepsis; however, no studies have examined the biological significance or clinical relevance of ANXA3 in this pathology. Here we explored this interpretation gap and identified possible directions for future research. Based on reference transcriptome datasets, we found that ANXA3 expression is restricted to neutrophils, is upregulated in vitro after exposure to plasma obtained from septic patients, and is associated with adverse clinical outcomes. Secondly, an increase in ANXA3 transcript abundance was also observed in vivo, in the blood of septic patients in multiple independent studies. ANXA3 is known to mediate calcium-dependent granules-phagosome fusion in support of microbicidal activity in neutrophils. More recent work has also shown that ANXA3 enhances proliferation and survival of tumour cells via a Caspase-3-dependent mechanism. And this same molecule is also known to play a critical role in regulation of apoptotic events in neutrophils. Thus, we posit that during sepsis ANXA3 might either play a beneficial role, by facilitating microbial clearance and resolution of the infection; or a detrimental role, by prolonging neutrophil survival, which is known to contribute to sepsis-mediated organ damage.

Profiling the Salivary microbiome of the Qatari population.

BACKGROUND: The role of the human microbiome in human health and disease has been studied in various body sites. However, compared to the gut microbiome, where most of the research focus is, the salivary microbiome still bears a vast amount of information that needs to be revealed. This study aims to characterize the salivary microbiome composition in the Qatari population, and to explore specific microbial signatures that can be associated with various lifestyles and different oral conditions. MATERIALS AND METHODS: We characterized the salivary microbiome of 997 Qatari adults using high-throughput sequencing of the V1-V3 region of the 16S rRNA gene. RESULTS: In this study, we have characterized the salivary microbiome of 997 Qatari participants. Our data show that Bacteroidetes, Firmicutes, Actinobacteria and Proteobacteria are the common phyla isolated from the saliva samples, with Bacteroidetes being the most predominant phylum. Bacteroidetes was also more predominant in males versus females in the study cohort, although differences in the microbial diversity were not statistically significant. We also show that, a lower diversity of the salivary microbiome is observed in the elderly participants, with Prevotella and Treponema being the most significant genera. In participants with oral conditions such as mouth ulcers, bleeding or painful gum, our data show that Prevotella and Capnocytophaga are the most dominant genera as compared to the controls. Similar patterns were observed in participants with various smoking habits as compared to the non-smoking participants. Our data show that Streptococcus and Neisseria are more dominant among denture users, as compared to the non-denture users. Our data also show that, abnormal oral conditions are associated with a reduced microbial diversity and microbial richness. Moreover, in this study we show that frequent coffee drinkers have higher microbial diversity compared to the non-drinkers, indicating that coffee may cause changes to the salivary microbiome. Furthermore, tea drinkers show higher microbial richness as compared to the non-tea drinkers. CONCLUSION: This is the first study to assess the salivary microbiome in an Arab population, and one of the largest population-based studies aiming to the characterize the salivary microbiome composition and its association with age, oral health, denture use, smoking and coffee-tea consumption.

Microbiome as an Immunological Modifier.

Humans are living ecosystems composed of human cells and microbes. The microbiome is the collection of microbes (microbiota) and their genes. Recent breakthroughs in the high-throughput sequencing technologies have made it possible for us to understand the composition of the human microbiome. Launched by the National Institutes of Health in USA, the human microbiome project indicated that our bodies harbor a wide array of microbes, specific to each body site with interpersonal and intrapersonal variabilities. Numerous studies have indicated that several factors influence the development of the microbiome including genetics, diet, use of antibiotics, and lifestyle, among others. The microbiome and its mediators are in a continuous cross talk with the host immune system; hence, any imbalance on one side is reflected on the other. Dysbiosis (microbiota imbalance) was shown in many diseases and pathological conditions such as inflammatory bowel disease, celiac disease, multiple sclerosis, rheumatoid arthritis, asthma, diabetes, and cancer. The microbial composition mirrors inflammation variations in certain disease conditions, within various stages of the same disease; hence, it has the potential to be used as a biomarker.

Influence of moderate beer consumption on human gut microbiota and its impact on fasting glucose and ß-cell function.

Beer is a beverage that has been consumed worldwide for thousands of years due to social, religious, and cultural reasons; it contains polyphenolic compounds as well as phenolic acids with a potential positive effect on human health. This study aimed to explore the impact of moderate beer consumption on human health and gut microbiota diversity. Three hundred fifty-five mL of non-alcoholic beer (NAB) or alcoholic beer (AB) were consumed daily by the participants for 30 days in each study. Anthropometric measures, blood samples for biochemistry, and fecal samples for microbiota analysis were collected on Day 1 and Day 30. Microbial diversity was characterized by high-throughput sequencing of 16S rDNA libraries, and data were analyzed using the QIIME pipeline. We found that NAB and AB have effects on the composition of the gut microbiota, favoring the proliferation of Bacteroidetes with respect to Firmicutes. No increase in weight, waist, and hip parameters was observed, and the liver and lipid profile values were not modified for NAB. In addition, the consumption of NAB induced a decrease in fasting blood serum glucose and an increase in functional ß cells, while, on the other hand, there was an increase in blood serum glucose and a decrease in functional ß cells with the consumption of AB. In general, beer consumption neither changed anthropometric values, nor affected liver function. Although the glucose values decreased with NAB or increased with AB, they remained within the normal range. Our conclusion is that moderate consumption of NAB has a positive effect on human health via supplementation of biological active polyphenol and phenolic acids, and by enrichment of the gut microbiota diversity with beneficial bacteria, while the presence of alcohol in AB interferes with this effect. More work should be done on this topic before general conclusions are drawn.