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.

Exploring the potential of microRNA as a diagnostic tool for gestational diabetes.

MicroRNAs (miRNAs) are small non-coding RNAs that play critical roles in regulating host gene expression. Recent studies have indicated a role of miRNAs in the pathogenesis of gestational diabetes mellitus (GDM), a common pregnancy-related disorder characterized by impaired glucose metabolism. Aberrant expression of miRNAs has been observed in the placenta and/or maternal blood of GDM patients, suggesting their potential use as biomarkers for early diagnosis and prognosis. Additionally, several miRNAs have been shown to modulate key signaling pathways involved in glucose homeostasis, insulin sensitivity, and inflammation, providing insights into the pathophysiology of GDM. This review summarizes the current knowledge on the dynamics of miRNA in pregnancy, their role in GDM as well as their potential as diagnostic and therapeutic targets.

Maternal microbiota and gestational diabetes: impact on infant health.

Gestational diabetes mellitus (GDM) is a common complication of pregnancy that has been associated with an increased risk of obesity and diabetes in the offspring. Pregnancy is accompanied by tightly regulated changes in the endocrine, metabolic, immune, and microbial systems, and deviations from these changes can alter the mother's metabolism resulting in adverse pregnancy outcomes and a negative impact on the health of her infant. Maternal microbiomes are significant drivers of mother and child health outcomes, and many microbial metabolites are likely to influence the host health. This review discusses the current understanding of how the microbiota and microbial metabolites may contribute to the development of GDM and how GDM-associated changes in the maternal microbiome can affect infant's health. We also describe microbiota-based interventions that aim to improve metabolic health and outline future directions for precision medicine research in this emerging field.

Unveiling the dynamics of the breast milk microbiome: impact of lactation stage and gestational age.

BACKGROUND: Breast milk (BM) provides complete nutrition for infants for the first six months of life and is essential for the development of the newborn's immature immune and digestive systems. While BM was conventionally believed to be sterile, recent advanced high throughput technologies have unveiled the presence of diverse microbial communities in BM. These insights into the BM microbiota have mainly originated from uncomplicated pregnancies, possibly not reflecting the circumstances of mothers with pregnancy complications like preterm birth (PTB). METHODS: In this article, we investigated the BM microbial communities in mothers with preterm deliveries (before 37 weeks of gestation). We compared these samples with BM samples from healthy term pregnancies across different lactation stages (colostrum, transitional and mature milk) using 16S rRNA gene sequencing. RESULTS: Our analysis revealed that the microbial communities became increasingly diverse and compositionally distinct as the BM matured. Specifically, mature BM samples were significantly enriched in Veillonella and lactobacillus (Kruskal Wallis; p < 0.001) compared to colostrum. The comparison of term and preterm BM samples showed that the community structure was significantly different between the two groups (Bray Curtis and unweighted unifrac dissimilarity; p < 0.001). Preterm BM samples exhibited increased species richness with significantly higher abundance of Staphylococcus haemolyticus, Propionibacterium acnes, unclassified Corynebacterium species. Whereas term samples were enriched in Staphylococcus epidermidis, unclassified OD1, and unclassified Veillonella among others. CONCLUSION: Our study underscores the significant influence of pregnancy-related complications, such as preterm birth (before 37 weeks of gestation), on the composition and diversity of BM microbiota. Given the established significance of the maternal microbiome in shaping child health outcomes, this investigation paves the way for identifying modifiable factors that could optimize the composition of BM microbiota, thereby promoting maternal and infant health.

The potential impact of a probiotic: Akkermansia muciniphila in the regulation of blood pressure-the current facts and evidence.

Akkermansia muciniphila (A. muciniphila) is present in the human gut microbiota from infancy and gradually increases in adulthood. The potential impact of the abundance of A. muciniphila has been studied in major cardiovascular diseases including elevated blood pressure or hypertension (HTN). HTN is a major factor in premature death worldwide, and approximately 1.28 billion adults aged 30-79 years have hypertension. A. muciniphila is being considered a next-generation probiotic and though numerous studies had highlighted the positive role of A. muciniphila in lowering/controlling the HTN, however, few studies had highlighted the negative impact of increased abundance of A. muciniphila in the management of HTN. Thus, in the review, we aimed to discuss the current facts, evidence, and controversy about the role of A. muciniphila in the pathophysiology of HTN and its potential effect on HTN management/regulation, which could be beneficial in identifying the drug target for the management of HTN.

Microbiota medicine: towards clinical revolution.

The human gastrointestinal tract is inhabited by the largest microbial community within the human body consisting of trillions of microbes called gut microbiota. The normal flora is the site of many physiological functions such as enhancing the host immunity, participating in the nutrient absorption and protecting the body against pathogenic microorganisms. Numerous investigations showed a bidirectional interplay between gut microbiota and many organs within the human body such as the intestines, the lungs, the brain, and the skin. Large body of evidence demonstrated, more than a decade ago, that the gut microbial alteration is a key factor in the pathogenesis of many local and systemic disorders. In this regard, a deep understanding of the mechanisms involved in the gut microbial symbiosis/dysbiosis is crucial for the clinical and health field. We review the most recent studies on the involvement of gut microbiota in the pathogenesis of many diseases. We also elaborate the different strategies used to manipulate the gut microbiota in the prevention and treatment of disorders. The future of medicine is strongly related to the quality of our microbiota. Targeting microbiota dysbiosis will be a huge challenge.

Inflammatory Bowel Disease Treatments and Predictive Biomarkers of Therapeutic Response.

Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammation of the gastrointestinal tract with a highly heterogeneous presentation. It has a relapsing and remitting clinical course that necessitates lifelong monitoring and treatment. Although the availability of a variety of effective therapeutic options including immunomodulators and biologics (such as TNF, CAM inhibitors) has led to a paradigm shift in the treatment outcomes and clinical management of IBD patients, some patients still either fail to respond or lose their responsiveness to therapy over time. Therefore, according to the recent Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE-II) recommendations, continuous disease monitoring from symptomatic relief to endoscopic healing along with short- and long-term therapeutic responses are critical for providing IBD patients with a tailored therapy algorithm. Moreover, considering the high unmet need for novel therapeutic approaches for IBD patients, various new modulators of cytokine signaling events (for example, JAK/TYK inhibitors), inhibitors of cytokines (for example IL-12/IL-23, IL-22, IL-36, and IL-6 inhibitors), anti-adhesion and migration strategies (for example, ß7 integrin, sphingosine 1-phosphate receptors, and stem cells), as well as microbial-based therapeutics to decolonize the bed buds (for example, fecal microbiota transplantation and bacterial inhibitors) are currently being evaluated in different phases of controlled clinical trials. This review aims to offer a comprehensive overview of available treatment options and emerging therapeutic approaches for IBD patients. Furthermore, predictive biomarkers for monitoring the therapeutic response to different IBD therapies are also discussed.

Gut microbial influences on the adaptive immune system and the development of cow milk allergy.

Allergic diseases constitute significant health and economic issues in both developed and developing nations, with epidemiological studies demonstrating a rapid increase in the global prevalence of food allergy among the pediatric population. Cow milk protein allergy (CMPA), one of the most common forms of food allergies observed in early childhood, affects between 2%-6% of infants and children under 3 years of age. CMPA can present as either an IgE-mediated atopic allergy or a non-IgE mediated allergic response. Antigen-specific T cells play a pivotal role in directing the type of inflammatory immune response that occurs as well as in the formation of immunological memory. IgE-mediated CMPA is thought to develop because of an abnormal expansion of allergen-specific type-2 helper T (Th2) cells and a corresponding deficiency in immune regulation by regulatory T cells (Tregs), thereby altering the Th2/Treg balance. The gut microbiota, established very early during childhood through host-microbe interactions, can influence the incidence of allergic diseases. In this study, we aimed to analyze both the microbiome composition and CD4+T cell differentiation patterns in pediatric patients with and without cow milk allergy to establish the association between these factors. Using 16S rRNA sequencing, we analyzed the microbiome composition in stool samples of allergic and non-allergic pediatric patients aged between 1-4 years and identified the microbial species abundant in IgE and non-IgE mediated cow milk allergies. To assess the CD4+T cell differentiation patterns, peripheral blood mononuclear cells (PBMCs) from these patients were re-stimulated with cow milk antigen, and T cell subsets were assessed using flow cytometry. Antigen-specific CD4+T cells were identified and sorted for high throughput sequencing and subsequent gene expression analysis. The CD4+T cell differentiation patterns of the total and antigen-specific T cells were analyzed and statistically compared with controls. The identification of the correlation between the CD4+T cell differentiation patterns and species-specific microbial abundance in IgE and non-IgE mediated cow milk allergies can help in determining how the gut microbiome influences the CD4+T cell immune compartment development, ultimately leading to the development of cow milk allergy in pediatric patients.

Omouma: a prospective mother and child cohort aiming to identify early biomarkers of pregnancy complications in women living in Qatar.

BACKGROUND: Pregnancy is governed by multiple molecular and cellular processes, which might influence pregnancy health and outcomes. Failure to predict and understand the cause of pregnancy complications, adverse pregnancy outcomes, infant's morbidity and mortality, have limited effective interventions. Integrative multi-omics technologies provide an unbiased platform to explore the complex molecular interactions with an unprecedented depth. The objective of the present protocol is to build a longitudinal mother-baby cohort and use multi-omics technologies to help identify predictive biomarkers of adverse pregnancy outcomes, early life determinants and their effect on child health. METHODS/DESIGN: One thousand pregnant women with a viable pregnancy in the first trimester (6-14 weeks of gestation) will be recruited from Sidra Medicine hospital. All the study participants will be monitored every trimester, at delivery, and one-year post-partum. Serial high-frequency sampling, including blood, stool, urine, saliva, skin, and vaginal swabs (mother only) from the pregnant women and their babies, will be collected. Maternal and neonatal health, including mental health and perinatal growth, will be recorded using a combination of questionnaires, interviews, and medical records. Downstream sample processing including microbial profiling, vaginal immune response, blood transcriptomics, epigenomics, and metabolomics will be performed. DISCUSSION: It is expected that the present study will provide valuable insights into predicting pregnancy complications and neonatal health outcomes. Those include whether specific microbial and/or epigenomics signatures, immune profiles are associated with a healthy pregnancy and/or complicated pregnancy and poor neonatal health outcome. Moreover, this non-interventional cohort will also serve as a baseline dataset to understand how familial, socioeconomic, environmental and lifestyle factors interact with genetic determinants to influence health outcomes later in life. These findings will hold promise for the diagnosis and precision-medicine interventions.

Distinctive Microbial Signatures and Gut-Brain Crosstalk in Pediatric Patients with Coeliac Disease and Type 1 Diabetes Mellitus.

Coeliac disease (CD) and Type 1 diabetes mellitus (T1DM) are immune-mediated diseases. Emerging evidence suggests that dysbiosis in the gut microbiome plays a role in the pathogenesis of both diseases and may also be associated with the development of neuropathy. The primary goal in this cross-sectional pilot study was to identify whether there are distinct gut microbiota alterations in children with CD (n = 19), T1DM (n = 18) and both CD and T1DM (n = 9) compared to healthy controls (n = 12). Our second goal was to explore the relationship between neuropathy (corneal nerve fiber damage) and the gut microbiome composition. Microbiota composition was determined by 16S rRNA gene sequencing. Corneal confocal microscopy was used to determine nerve fiber damage. There was a significant difference in the overall microbial diversity between the four groups with healthy controls having a greater microbial diversity as compared to the patients. The abundance of pathogenic proteobacteria Shigella and E. coli were significantly higher in CD patients. Differential abundance analysis showed that several bacterial amplicon sequence variants (ASVs) distinguished CD from T1DM. The tissue transglutaminase antibody correlated significantly with a decrease in gut microbial diversity. Furthermore, the Bacteroidetes phylum, specifically the genus Parabacteroides was significantly correlated with corneal nerve fiber loss in the subjects with neuropathic damage belonging to the diseased groups. We conclude that disease-specific gut microbial features traceable down to the ASV level distinguish children with CD from T1DM and specific gut microbial signatures may be associated with small fiber neuropathy. Further research on the mechanisms linking altered microbial diversity with neuropathy are warranted.

Immunomodulatory Effects of Vitamin D Supplementation in a Deficient Population.

In addition to its canonical functions, vitamin D has been proposed to be an important mediator of the immune system. Despite ample sunshine, vitamin D deficiency is prevalent (>80%) in the Middle East, resulting in a high rate of supplementation. However, the underlying molecular mechanisms of the specific regimen prescribed and the potential factors affecting an individual's response to vitamin D supplementation are not well characterized. Our objective is to describe the changes in the blood transcriptome and explore the potential mechanisms associated with vitamin D3 supplementation in one hundred vitamin D-deficient women who were given a weekly oral dose (50,000 IU) of vitamin D3 for three months. A high-throughput targeted PCR, composed of 264 genes representing the important blood transcriptomic fingerprints of health and disease states, was performed on pre and post-supplementation blood samples to profile the molecular response to vitamin D3. We identified 54 differentially expressed genes that were strongly modulated by vitamin D3 supplementation. Network analyses showed significant changes in the immune-related pathways such as TLR4/CD14 and IFN receptors, and catabolic processes related to NF-kB, which were subsequently confirmed by gene ontology enrichment analyses. We proposed a model for vitamin D3 response based on the expression changes of molecules involved in the receptor-mediated intra-cellular signaling pathways and the ensuing predicted effects on cytokine production. Overall, vitamin D3 has a strong effect on the immune system, G-coupled protein receptor signaling, and the ubiquitin system. We highlighted the major molecular changes and biological processes induced by vitamin D3, which will help to further investigate the effectiveness of vitamin D3 supplementation among individuals in the Middle East as well as other regions.

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.

Pathophysiology and treatment strategies for COVID-19.

The outbreak of Coronavirus disease of 2019 (COVID-19) caused by the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), has posed a serious health threat. The increasing number of COVID-19 cases around the world is overwhelming hospitals and pushing the global death toll to over 746,000, which has pushed the sprint to find new treatment options. In this article, we reviewed the SARS-CoV-2 pathophysiology, transmission, and potential treatment strategies.

A literature-based approach for curating gene signatures in multifaceted diseases.

BACKGROUND AND AIMS: The task of identifying a representative and yet manageable target gene list for assessing the pathogenesis of complicated and multifaceted diseases is challenging. Using Inflammatory Bowel Disease (IBD) as an example, we conceived a bioinformatic approach to identify novel genes associated with the various disease subtypes, in combination with known clinical control genes. METHODS: From the available literature, we used Acumenta Literature LabTM (LitLab), network analyses, and LitLab Gene Retriever to assemble a gene pool that has a high likelihood of representing immunity-related subtype-specific signatures of IBD. RESULTS: We generated six relevant gene lists and 21 intersections that contain genes with unique literature associations to Crohn's Disease (n = 60), Ulcerative Colitis (n = 17), and unclassified (n = 45) subtypes of IBD. From this gene pool, we then filtered and constructed, using network analysis, a final list of 142 genes that are the most representative of the disease and its subtypes. CONCLUSIONS: In this paper, we present the bioinformatic construction of a gene panel that putatively contains subtype signatures of IBD, a multifactorial disease. These gene signatures will be tested as biomarkers to classify patients with IBD, which has been a clinically challenging task. Such approach to diagnose and monitor complicated disease pathogenesis is a stepping-stone towards personalized care.

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.

Role of the gut microbiota in the pathogenesis of coeliac disease and potential therapeutic implications.

PURPOSE: Although genetic predisposition and exposure to dietary gluten are considered necessary triggers for the development of coeliac disease, alterations in the gut microbial composition may also contribute towards the pathogenesis of coeliac disease. This review aims to provide an overview of the available data on the potential mechanisms through which the gut microbiota plays a role in the causation of coeliac disease and to discuss the potential therapeutic strategies that could diminish the consequences of microbial dysbiosis. METHOD: A search of the literature was performed using the PubMed, Embase, and JSTOR databases; relevant articles were included. RESULTS: Recent studies in patients with coeliac disease have reported an increase in the relative amounts of gram negative bacterial genera such as Bacteroides, Prevotella, and Escherichia, and reduced amounts of protective anti-inflammatory bacteria such as Bifidobacteria and Lactobacilli. Dysbiotic microbiota may lead to a dysregulated immune response that may contribute to the pathogenesis of coeliac disease. In infancy, antibiotic use and certain infant feeding practices may lead to alterations in the developing gut microbiota to influence the immune maturation process and predispose to coeliac disease. CONCLUSION: The induction of the intestinal immune system and gluten intolerance may be influenced by the relative abundance of certain microbiota. Factors such as infant feeding practices, diet, antibiotics, and infections, may be involved in the development of coeliac disease due to their influence on gut microbial composition. The efficacy of potential modulators of the gut microbiota such as probiotics, prebiotics, and fecal microbial transplant as adjunctive treatments to gluten-free diet in coeliac disease is unproven and requires further investigation.

Exploring the Triple Interaction between the Host Genome, the Epigenome, and the Gut Microbiome in Type 1 Diabetes.

Type 1 diabetes (T1D) is an auto-immune disorder characterized by a complex interaction between the host immune system and various environmental factors in genetically susceptible individuals. Genome-wide association studies (GWAS) identified different T1D risk and protection alleles, however, little is known about the environmental factors that can be linked to these alleles. Recent evidence indicated that, among those environmental factors, dysbiosis (imbalance) in the gut microbiota may play a role in the pathogenesis of T1D, affecting the integrity of the gut and leading to systemic inflammation and auto-destruction of the pancreatic ß cells. Several studies have identified changes in the gut microbiome composition in humans and animal models comparing T1D subjects with controls. Those changes were characterized by a higher abundance of Bacteroides and a lower abundance of the butyrate-producing bacteria such as Clostridium clusters IV and XIVa. The mechanisms by which the dysbiotic bacteria and/or their metabolites interact with the genome and/or the epigenome of the host leading to destructive autoimmunity is still not clear. As T1D is a multifactorial disease, understanding the interaction between different environmental factors such as the gut microbiome, the genetic and the epigenetic determinants that are linked with the early appearance of autoantibodies can expand our knowledge about the disease pathogenesis. This review aims to provide insights into the interaction between the gut microbiome, susceptibility genes, epigenetic factors, and the immune system in the pathogenesis of T1D.

Integrating omics for a better understanding of Inflammatory Bowel Disease: a step towards personalized medicine.

BACKGROUND: Inflammatory Bowel Disease (IBD) is a multifactorial chronic disease. Understanding only one aspect of IBD pathogenesis does not reflect the complex nature of IBD nor will it improve its clinical management. Therefore, it is vital to dissect the interactions between the different players in IBD pathogenesis in order to understand the biology of the disease and enhance its clinical outcomes. AIMS: To provide an overview of the available omics data used to assess the potential mechanisms through which various players are contributing to IBD pathogenesis and propose a precision medicine model to fill the current knowledge gap in IBD. RESULTS: Several studies have reported microbial dysbiosis, immune and metabolic dysregulation in IBD patients, however, this data is not sufficient to create signatures that can differentiate between the disease subtypes or between disease relapse and remission. CONCLUSIONS: We summarized the current knowledge in the application of omics in IBD patients, and we showed that the current knowledge gap in IBD hinders the improvements of clinical decision for treatment as well as the prediction of disease relapse. We propose one way to fill this gap by implementing integrative analysis of various omics datasets generated from one patient at a single time point.

Activator of G-Protein Signaling 3-Induced Lysosomal Biogenesis Limits Macrophage Intracellular Bacterial Infection.

Many intracellular pathogens cause disease by subverting macrophage innate immune defense mechanisms. Intracellular pathogens actively avoid delivery to or directly target lysosomes, the major intracellular degradative organelle. In this article, we demonstrate that activator of G-protein signaling 3 (AGS3), an LPS-inducible protein in macrophages, affects both lysosomal biogenesis and activity. AGS3 binds the Gi family of G proteins via its G-protein regulatory (GoLoco) motif, stabilizing the Gα subunit in its GDP-bound conformation. Elevated AGS3 levels in macrophages limited the activity of the mammalian target of rapamycin pathway, a sensor of cellular nutritional status. This triggered the nuclear translocation of transcription factor EB, a known activator of lysosomal gene transcription. In contrast, AGS3-deficient macrophages had increased mammalian target of rapamycin activity, reduced transcription factor EB activity, and a lower lysosomal mass. High levels of AGS3 in macrophages enhanced their resistance to infection by Burkholderia cenocepacia J2315, Mycobacterium tuberculosis, and methicillin-resistant Staphylococcus aureus, whereas AGS3-deficient macrophages were more susceptible. We conclude that LPS priming increases AGS3 levels, which enhances lysosomal function and increases the capacity of macrophages to eliminate intracellular pathogens.