Dr. Gubatan is a physician scientist, gastroenterologist, and instructor of medicine at Stanford University School of Medicine. He earned his medical degree from Harvard Medical School and completed his internship and residency in internal medicine at Harvard's Beth Israel Deaconess Medical Center. He completed his gastroenterology fellowship at Stanford where he served as chief fellow and was an American Gastroenterological Association (AGA) editorial fellow for Gastroenterology. Dr. Gubatan’s research is focused on translational studies using single-cell genomics to understand mechanisms of biologic therapy failure, elucidate the role of host immune and gut microbiome interactions in the pathogenesis of inflammatory bowel disease (IBD), and develop precision medicine strategies to improve outcomes in patients with IBD. Dr. Gubatan’s work has been featured in Gastroenterology, Gut, American Journal of Gastroenterology, Clinical Gastroenterology and Hepatology, Alimentary Pharmacology and Therapeutics, Journal of Crohns & Colitis, and Inflammatory Bowel Diseases. Dr. Gubatan's research and career development has been supported by a Chan Zuckerberg Biohub Physician Scientist Scholar Award, a Stanford Translational Research and Applied Medicine (TRAM) Scholar Award, an NIH NIDDK LRP Award, and a Doris Duke Charitable Foundation Physician Scientist Fellowship Award.
- Inflammatory Bowel Disease
- Ulcerative Colitis
- Crohn's Disease
Instructor, Medicine - Gastroenterology & Hepatology
Honors & Awards
Doris Duke Physician Scientist Fellowship Award, Doris Duke Charitable Foundation (DDCF) (2021-2023)
ACG Outstanding Poster Presenter Award, American College of Gastroenterology (ACG) (2021)
NCSCG Symposium 1st Place Abstract Award, Northern California Society for Clinical Gastroenterology (2021)
Best Original Basic Science Article of 2020 Finalist, Inflammatory Bowel Diseases Journal (2020)
Chief Fellow, Division of Gastroenterology and Hepatology, Stanford University (2020-2021)
Chan Zuckerberg Biohub Physician Scientist Scholar Award, Chan Zuckerberg Biohub (2020-2022)
AGA Gastroenterology Editorial Fellow, American Gastroenterological Association (AGA) (2020-2021)
Clinical Research Loan Repayment Program (LRP) Award, National Institutes of Health (NIH)/NIDDK (2020-2022)
Stanford Translational Research and Applied Medicine (TRAM) Scholar Award, Stanford University (2020-2022)
Top Downloaded Paper Award in Alimentary Pharmacology & Therapeutics, Wiley Publishing (2020)
Outstanding Reviewer Award, Experimental Biology and Medicine (2019)
Robert W. Summers Grant Award, American Society for Gastrointestinal Endoscopy (ASGE) (2019)
Third Annual Inflammatory Bowel Disease (IBD) Summit for Fellows Travel Award, Vindico Medical Education (2019)
Senior Resident Medicine Grand Rounds Research Award, Beth Israel Deaconess Medical Center, Harvard University (2017)
Harvard Open Access Publishing Equity (HOPE) Award, Harvard University (2016)
Outstanding Abstract Award, Resident & Fellow Poster Competition, Beth Israel Deaconess Medical Center, Harvard (2016)
Harvard Medical School Class of 1951 Endowed Scholarship, Harvard Medical School (2013)
Harvard Dean Advisory Council Meeting Immunology Research Award, Harvard University (2011)
Harvard Medical School Research Fellowship, Harvard Medical School (2011)
Ambassador Award, Department of Chemistry, Michigan Tech University (2010)
Outstanding Senior Award, Department of Chemistry, Michigan Tech University (2010)
Summa Cum Laude, Michigan Tech University (2010)
Amgen Scholarship, Stanford University School of Medicine (2009)
Barry M. Goldwater Scholarship, The Barry Goldwater Scholarship and Excellence in Education Foundation (2009)
Summer Honors Undergraduate Research Program (SHURP), Harvard University (2008)
Summer Medical And Research Training (SMART) Program, Baylor College of Medicine (2007)
Government of Guam Merit Scholar, University of Guam (2006-2007)
NIH Research Initiative for Scientific Enhancement (RISE) Fellowship, University of Guam (2006-2007)
Boards, Advisory Committees, Professional Organizations
Member, American Gastroenterological Association (AGA) (2016 - Present)
Member, American College of Gastroenterology (ACG) (2016 - Present)
Member, Crohn’s & Colitis Foundation (CCF) (2019 - Present)
Member, European Crohn’s and Colitis Organisation (ECCO) (2016 - Present)
Member, Cochrane Collaboration (2020 - Present)
Member, American Society of Gastrointestinal Endoscopy (ASGE) (2018 - Present)
Board Certification: American Board of Internal Medicine, Gastroenterology (2021)
Fellowship: Stanford University Gastroenterology Fellowship (2021) CA
Board Certification: American Board of Internal Medicine, Internal Medicine (2017)
Residency: Beth Israel Deaconess Medical Center Internal Medicine Residency (2017) MA
Medical Education: Harvard Medical School (2014) MA
Fellowship, Stanford University School of Medicine, Gastroenterology (2021)
Residency, Beth Israel Deaconess Medical Center, Harvard Medical School, Internal Medicine (2017)
M.D., Harvard Medical School, Medicine (2014)
B.S., Michigan Tech University, Biochemistry and Molecular Biology (2010)
Vitamin D Regulation of Gut Specific B Cells and Antibodies Targeting Gut Bacteria in Inflammatory Bowel Disease
Specific Aim 1: Characterize the effects of vitamin D treatment on expression of α4β7 on B cells in patients with inflammatory bowel disease (IBD). Specific Aim 2: Determine the effects of vitamin D treatment on fecal immunoglobulins, percentage of Ig-coated gut bacteria, gut microbiome composition (global and bound by immunoglobulins) in patients with IBD and the association of these parameters with change in α4β7+ B cells . Specific Aim 3: Compare BCR repertoire (BCR clonotypes, immunoglobulin heavy chain gene (IGHV), and isotype usage) between α4β7+ and α4β7- B cells in patients with IBD and identify α4β7+ BCR clonotypes associated with Ig-bound gut bacteria .
Graduate and Fellowship Programs
Gastroenterology & Hepatology (Fellowship Program)
Disease exacerbation is common in inflammatory bowel disease patients treated with immune checkpoint inhibitors for malignancy.
World journal of clinical cases
2022; 10 (6): 1787-1794
Colitis is a known potential toxicity of immune checkpoint inhibitors (ICIs). Studies evaluating the risk of disease exacerbation following ICI treatment in patients with pre-existing inflammatory bowel disease (IBD) are limited.To assess the clinical characteristics of IBD patients treated with ICIs and determine prevalence of subsequent IBD exacerbations.We conducted a retrospective cohort study of all patients in the Stanford Research Repository database with pre-existing IBD who were exposed to ICIs.The prevalence of IBD exacerbation following ICI was 36.8% amongst 19 patients meeting inclusion criteria. Patients with exacerbations had more gastrointestinal-related hospitalizations (4 of 7) than patients without exacerbations (0 of 12; P = 0.0090).The prevalence of IBD exacerbations following ICI was higher than reported rates of ICI-induced colitis and diarrhea in the general population and was associated with hospitalization.
View details for DOI 10.12998/wjcc.v10.i6.1787
View details for PubMedID 35317167
View details for PubMedCentralID PMC8891792
Selective tyrosine kinase 2 inhibitors in inflammatory bowel disease.
Trends in pharmacological sciences
Recent significant advances have been made in the treatment of chronic inflammatory diseases with initiation of the era of biologics. However, an unmet medical need still exists for novel targeted therapies. Compared with biologics, Janus kinase inhibitors (JAKis) are a new drug class of orally administered small molecules that have been shown to efficiently modulate complex cytokine-driven inflammation in preclinical models and human studies. Unfortunately, serious adverse effects have been reported with the first introduced pan-JAKi, tofacitinib. Here, we review tyrosine kinase 2 (TYK2) signaling in the pathophysiology of inflammatory bowel disease (IBD), examine mechanisms of action of selective TYK2 inhibitors (TYK2is), and discuss the potential for these inhibitors in efforts to balance benefits and harms.
View details for DOI 10.1016/j.tips.2022.02.008
View details for PubMedID 35277286
Antimicrobial peptides and the gut microbiome in inflammatory bowel disease.
World journal of gastroenterology
2021; 27 (43): 7402-7422
Antimicrobial peptides (AMP) are highly diverse and dynamic molecules that are expressed by specific intestinal epithelial cells, Paneth cells, as well as immune cells in the gastrointestinal (GI) tract. They play critical roles in maintaining tolerance to gut microbiota and protecting against enteric infections. Given that disruptions in tolerance to commensal microbiota and loss of barrier function play major roles in the pathogenesis of inflammatory bowel disease (IBD) and converge on the function of AMP, the significance of AMP as potential biomarkers and novel therapeutic targets in IBD have been increasingly recognized in recent years. In this frontier article, we discuss the function and mechanisms of AMP in the GI tract, examine the interaction of AMP with the gut microbiome, explore the role of AMP in the pathogenesis of IBD, and review translational applications of AMP in patients with IBD.
View details for DOI 10.3748/wjg.v27.i43.7402
View details for PubMedID 34887639
View details for PubMedCentralID PMC8613745
Anti-Integrins for the Treatment of Inflammatory Bowel Disease: Current Evidence and Perspectives.
Clinical and experimental gastroenterology
2021; 14: 333-342
Leukocyte trafficking to the gastrointestinal tract is recognized to play a role in the pathogenesis of inflammatory bowel disease (IBD). Integrins are expressed on immune cells and interact with cell adhesion molecules (CAM) to mediate leukocyte trafficking. Blockade of the gut-tropic integrin α4β7 and its subunits has been exploited as a therapeutic target in IBD. Natalizumab (anti-α4) is approved for moderate to severe Crohn's disease (CD), but its use is limited due to potential risk of progressive multifocal leukoencephalopathy. Vedolizumab (anti-α4β7) is approved for the treatment of ulcerative colitis (UC) and CD. It is the most widely used anti-integrin therapy in IBD and has been shown to be effective in both induction and maintenance therapy, with a favorable safety profile. Several models incorporating clinical, genetic, immune, gut microbial, and vitamin D markers to predict response to vedolizumab in IBD have been developed. Etrolizumab (anti-β7) blocks leukocyte trafficking via α4β7 and cell adhesion via αEβ7 integrins. Large phase 3 clinical trials evaluating efficacy of etrolizumab in the induction and maintenance of patients with IBD are underway. Other investigational anti-integrin therapies include abrilumab (anti-α4β7 IgG2), PN-943 (orally administered and gut-restricted α4β7 antagonist peptide), AJM300 (orally active small molecule inhibitor of α4), and ontamalimab (anti-MAdCAM-1 IgG).
View details for DOI 10.2147/CEG.S293272
View details for PubMedID 34466013
View details for PubMedCentralID PMC8402953
Dual targeting of lymphocyte homing and retention through α4β7 and αEβ7 inhibition in inflammatory bowel disease.
Cell reports. Medicine
2021; 2 (8): 100381
Anti-integrins are therapeutically effective for inflammatory bowel disease, yet the relative contribution of α4β7 and αEβ7 to gut lymphocyte trafficking is not fully elucidated. Here, we evaluate the effect of α4β7 and αEβ7 blockade using a combination of murine models of gut trafficking and longitudinal gene expression analysis in etrolizumab-treated patients with Crohn's disease (CD). Dual blockade of α4β7 and αEβ7 reduces CD8+ T cell accumulation in the gut to a greater extent than blockade of either integrin alone. Anti-αEβ7 reduces epithelial:T cell interactions and promotes egress of activated T cells from the mucosa into lymphatics. Inflammatory gene expression is greater in human intestinal αEβ7+ T cells. Etrolizumab-treated patients with CD display a treatment-specific reduction in inflammatory and cytotoxic intraepithelial lymphocytes (IEL) genes. Concurrent blockade of α4β7 and αEβ7 promotes reduction of cytotoxic IELs and inflammatory T cells in the gut mucosa through a stepwise inhibition of intestinal tissue entry and retention.
View details for DOI 10.1016/j.xcrm.2021.100381
View details for PubMedID 34467254
View details for PubMedCentralID PMC8385326
Artificial intelligence applications in inflammatory bowel disease: Emerging technologies and future directions.
World journal of gastroenterology
2021; 27 (17): 1920-1935
Inflammatory bowel disease (IBD) is a complex and multifaceted disorder of the gastrointestinal tract that is increasing in incidence worldwide and associated with significant morbidity. The rapid accumulation of large datasets from electronic health records, high-definition multi-omics (including genomics, proteomics, transcriptomics, and metagenomics), and imaging modalities (endoscopy and endomicroscopy) have provided powerful tools to unravel novel mechanistic insights and help address unmet clinical needs in IBD. Although the application of artificial intelligence (AI) methods has facilitated the analysis, integration, and interpretation of large datasets in IBD, significant heterogeneity in AI methods, datasets, and clinical outcomes and the need for unbiased prospective validations studies are current barriers to incorporation of AI into clinical practice. The purpose of this review is to summarize the most recent advances in the application of AI and machine learning technologies in the diagnosis and risk prediction, assessment of disease severity, and prediction of clinical outcomes in patients with IBD.
View details for DOI 10.3748/wjg.v27.i17.1920
View details for PubMedID 34007130
View details for PubMedCentralID PMC8108036
Gastrointestinal symptoms and healthcare utilization have increased among patients with functional gastrointestinal and motility disorders during the COVID-19 pandemic.
Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
The coronavirus disease 2019 (COVID-19) pandemic has led to unprecedented disruptions in healthcare. Functional gastrointestinal and motility disorders (FGIMD) are associated with significant healthcare utilization. The clinical implications of these healthcare disruptions due to the COVID-19 pandemic on clinical outcomes in patients with FGIMD are unclear.We performed a retrospective study of patients with three common FGIMD (irritable bowel syndrome [IBS], gastroparesis, functional dyspepsia [FD]) tested for SARS-CoV-2 to describe alterations in gastrointestinal symptoms, medication use, and healthcare utilization during and before the pandemic and factors associated with COVID-19.The prevalence of COVID-19 during the pandemic (03/2020-09/2020) was 3.20% (83/2592) among patients with FGIMD, 3.62% in IBS (57/1574), 3.07% in gastroparesis (23/749), and 2.44% in FD (29/1187) at our institution. Patients with FGIMD had increased abdominal pain, nausea/vomiting, diarrhea, constipation, and weight loss (p < 0.001) along with increased proton pump inhibitor, H2 blocker, and opioid use (p < 0.0001). Both inpatient hospitalizations and outpatient visits (p < 0.0001) and number of diagnostic tests including cross-sectional imaging (p = 0.002), and upper and lower endoscopies (p < 0.0001) were significantly higher during the pandemic as compared to 6 months prior. Diarrhea-predominant IBS was positively (OR 2.37, 95% CI 1.34-4.19, p = 0.003) associated with COVID-19, whereas functional dyspepsia was negatively (OR 0.46, 95% CI 0.27-0.79, p = 0.004) associated.Patients with common functional gastrointestinal and motility disorders have reported more gastrointestinal symptoms during the COVID-19 pandemic with concurrent increased medication use and healthcare utilization.
View details for DOI 10.1111/nmo.14243
View details for PubMedID 34378840
Immune checkpoint inhibitor-mediated colitis in gastrointestinal malignancies and inflammatory bowel disease.
World journal of gastrointestinal oncology
2021; 13 (8): 772-798
Immune checkpoint inhibitors (ICI) have markedly changed the landscape of cancer therapy. By re-invigorating the immune system against tumors, ICI provide novel therapeutic options for a broad variety of malignancies, including many gastrointestinal (GI) cancers. However, these therapies can also induce autoimmune-like side effects in healthy tissue across the body. One of the most common of these side effects is ICI-mediated colitis and diarrhea (IMC). Here, we review the incidence and risk of IMC in ICI therapy, with a focus on what is known regarding IMC in patients with GI malignancies. We also discuss data available on the use of ICI and risk of IMC in patients with pre-existing inflammatory bowel disease, as these patients may have increased risk of IMC due to their underlying intestinal pathology.
View details for DOI 10.4251/wjgo.v13.i8.772
View details for PubMedID 34457186
View details for PubMedCentralID PMC8371513
- Reply to Letter to the Editor: What is the incidence of COVID-19 in patients with IBD in western countries? Gastroenterology 2021
Vitamin D is Associated with α4β7+ Immunophenotypes and Predicts Vedolizumab Therapy Failure in Patients with Inflammatory Bowel Disease.
Journal of Crohn's & colitis
Vitamin D downregulates the in vitro expression of the gut-tropic integrin α4β7 on immune cells. The clinical relevance of this finding in patients with inflammatory bowel disease (IBD) is unclear. We tested the hypothesis that vitamin D is associated with α4β7 immunophenotypes and risk of vedolizumab (anti- α4β7) failure in IBD.We performed single-cell immunophenotyping of peripheral and intestinal immune cells using mass cytometry (CyTOF) in vedolizumab-naïve patients with IBD (N=48). We analyzed whole-genome mucosal gene expression (GSE73661) from GEMINI I and GEMINI long-term safety (LTS) to determine the association between vitamin D receptor (VDR) and integrin alpha-4 (ITGA4) and beta-7 (ITGB7) genes. We estimated the odds of vedolizumab failure with low pre-treatment vitamin D in a combined retrospective and prospective IBD cohort (N= 252) with logistic regression.Immunophenotyping revealed that higher 25(OH)D was associated with decreased α4β7+ peripheral blood mononuclear cells (R = -0.400, P < 0.01) and α4β7+ intestinal leukocytes (R = -0.538, P= 0.03). Serum 25(OH)D was inversely associated with α4β7+ peripheral B cells and natural killer (NK) cells and α4β7+ intestinal B cells, NK cells, monocytes, and macrophages. Mucosal expression of VDR was inversely associated with ITGA4 and ITGB7 expression. In multivariate analysis, 25(OH)D < 25 ng/mL was associated with increased vedolizumab primary non-response during induction (OR 26.10, 95% CI 14.30-48.90, P<0.001) and failure at 1-year follow-up (OR 6.10, 95% CI 3.06-12.17, P<0.001).Low serum 25(OH)D is associated with α4β7+ immunophenotypes and predicts future vedolizumab failure in patients with IBD.
View details for DOI 10.1093/ecco-jcc/jjab114
View details for PubMedID 34180967
Gastric Mucosal Immune Profiling and Dysregulation in Idiopathic Gastroparesis.
Clinical and translational gastroenterology
2021; 12 (5): e00349
It is unclear how immune perturbations may influence the pathogenesis of idiopathic gastroparesis, a prevalent functional disorder of the stomach which lacks animal models. Several studies have noted altered immune characteristics in the deep gastric muscle layer associated with gastroparesis, but data are lacking for the mucosal layer, which is endoscopically accessible. We hypothesized that immune dysregulation is present in the gastroduodenal mucosa in idiopathic gastroparesis and that specific immune profiles are associated with gastroparesis clinical parameters.In this cross-sectional prospective case-control study, routine endoscopic biopsies were used for comprehensive immune profiling by flow cytometry, multicytokine array, and gene expression in 3 segments of the stomach and the duodenal bulb. Associations of immune endpoints with clinical parameters of gastroparesis were also explored.The gastric mucosa displayed large regional variation of distinct immune profiles. Furthermore, several-fold increases in innate and adaptive immune cells were found in gastroparesis. Various immune cell types showed positive correlations with duration of disease, proton pump inhibitor dosing, and delayed gastric emptying.This initial observational study showed immune compartmentalization of the human stomach mucosa and significant immune dysregulation at the level of leukocyte infiltration in idiopathic gastroparesis patients that extends to the duodenum. Select immune cells, such as macrophages, may correlate with clinicopathological traits of gastroparesis. This work supports further mucosal studies to advance our understanding of gastroparesis pathophysiology.
View details for DOI 10.14309/ctg.0000000000000349
View details for PubMedID 33979305
- Are Proton Pump Inhibitors Contributing to SARS-COV-2 Infection? The American journal of gastroenterology 2020
Mucosal vitamin D signaling in inflammatory bowel disease.
Epidemiological studies have identified vitamin D (25(OH)D) deficiency to be highly prevalent among patients with inflammatory bowel disease (IBD), and low serum levels correlate with a higher disease activity and a more complicated disease course. The link to IBD pathogenesis has been subject of investigations, primarily due to the distinct immunological functions of vitamin D signaling, including anti-inflammatory and anti-fibrotic actions. Vitamin D is a pleiotropic hormone that executes its actions on cells through the vitamin D receptor (VDR). A leaky gut, i.e. an insufficient intestinal epithelial barrier, is thought to be central for the pathogenesis of IBD, and emerging data support the concept that vitamin D/VDR signaling in intestinal epithelial cells (IECs) has an important role in controlling barrier integrity. Here we review the latest evidence on how vitamin D promotes the interplay between IECs, the gut microbiome, and immune cells and thereby regulate the intestinal immune response. On the cellular level, vitamin D signaling regulates tight junctional complexes, apoptosis, and autophagy, leading to increased epithelial barrier integrity, and promotes expression of antimicrobial peptides as part of its immunomodulating functions. Further, intestinal VDR expression is inversely correlated with the severity of inflammation in patients with IBD, which might compromise the positive effects of vitamin D signaling in patients with flaring disease. Efforts to reveal the role of vitamin D in the pathophysiology of IBD will pave the road for the invention of more rational treatment strategies of this debilitating disease in the future.
View details for DOI 10.1016/j.autrev.2020.102672
View details for PubMedID 32942038
Biologics for Inflammatory Bowel Disease and their Safety in Pregnancy: A Systematic Review and Meta-analysis.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
Biologics are routinely used in pregnant women with inflammatory bowel disease (IBD) but large-scale data reporting adverse pregnancy outcomes among biologic users are lacking. We sought to estimate the prevalence of adverse pregnancy outcomes in women with IBD on biologic therapies.We searched major databases from inception to June 2020 for studies estimating the prevalence of adverse pregnancy outcomes in IBD when using biologics (anti-TNF, anti-integrins, and anti-cytokines). Prevalence and relative risk (RR) were pooled using a random effects model.Forty-eight studies were included in the meta-analysis comprising 6963 patients. Biologic therapy in IBD pregnancies was associated with a pooled prevalence of 8% (95% CI 6-10%, I2= 87.4%) for early pregnancy loss, 9% (95% CI 7-11%, I2=89.9%) preterm birth, 0% (95% CI 0-0%, I2=0%) still birth, 8% (95% CI 5-10%, I2=87.0%) low birth weight, and 1% (95% CI 1-2%, I2=78.3%) congenital malformations. These rates are comparable to those published in the general population. In subgroup analyses of a small number of studies, the prevalence of early pregnancy loss and preterm birth were higher in vedolizumab versus anti-TNF users. Meta-regression did not reveal an association of disease activity or concomitant thiopurine on adverse outcomes. Continued TNF inhibitor use during the third trimester was not associated with risk of preterm birth (RR 1.41, 95% CI 0.77-2.60, I2=0%), low birth weight (RR 1.32, 95% CI 0.80-2.18, I2=0%), or congenital malformations (RR 1.28, 95% 0.47-3.49, I2=0%).Adverse pregnancy outcomes among pregnant IBD women with biologic use are comparable with that of the general population. PROSPERO protocol #CRD42019135721.
View details for DOI 10.1016/j.cgh.2020.09.021
View details for PubMedID 32931960
Biologics During Pregnancy in Women With Inflammatory Bowel Disease and Risk of Infantile Infections: A Systematic Review and Meta-Analysis.
The American journal of gastroenterology
Biologics, such as tumor necrosis factor inhibitors, anti-integrins and anticytokines, are therapies for inflammatory bowel disease (IBD) that may increase the risk of infection. Most biologics undergo placental transfer during pregnancy and persist at detectable concentrations in exposed infants. Whether this is associated with an increased risk of infantile infections is controversial. We performed a systematic review and meta-analysis evaluating the risk of infantile infections after in utero exposure to biologics used to treat IBD.We searched PubMed, Embase, Scopus, Web of Science, and CENTRAL from inception to June 2020 to evaluate the association of biologic therapy during pregnancy in women with IBD and risk of infantile infections. Odds ratios of outcomes were pooled and analyzed using a random effects model.Nine studies met the inclusion criteria comprising 8,013 women with IBD (5,212 Crohn's disease, 2,801 ulcerative colitis) who gave birth to 8,490 infants. Biologic use during pregnancy was not associated with an increased risk of all infantile infections (odds ratio [OR] 0.91, 95% confidence interval [CI] 0.73-1.14, I = 30%). In a subgroup analysis for the type of infection, biologic use was associated with increased infantile upper respiratory infections (OR 1.57, 95% CI 1.02-2.40, I = 4%). Biologic use during pregnancy was not associated with infantile antibiotic use (OR 0.91, 95% CI 0.73-1.14, I = 30%) or infection-related hospitalizations (OR 1.33, 95% CI 0.95-1.86, I = 26%).Biologics use during pregnancy in women with IBD is not associated with the overall risk of infantile infections or serious infections requiring antibiotics or hospitalizations but is associated with an increased risk of upper respiratory infections.
View details for DOI 10.14309/ajg.0000000000000910
View details for PubMedID 33110017
- SARS-CoV-2 Testing, Prevalence, and Predictors of COVID-19 in Patients with Inflammatory Bowel Disease in Northern California. Gastroenterology 2020
Gastric Leiomyosarcoma Unmasked by Bleeding From a Percutaneous Endoscopic Gastrostomy Tube.
ACG case reports journal
2020; 7 (1): e00301
Gastrointestinal bleeding from percutaneous endoscopic gastrostomy tubes and malignancy are uncommon. Gastric leiomyosarcomas are rare and differentiated from other gastric tumors with histology and immunohistochemical staining. We present a case of upper gastrointestinal bleeding from a percutaneous endoscopic gastrostomy tube manifesting as a gastric leiomyosarcoma in a 50-year-old man with a medical history of Wilms tumor. We reviewed the epidemiology, diagnosis, and management of gastric leiomyosarcomas. We also explored the risk factors and potential mechanisms in the pathogenesis of gastric leiomyosarcoma in our patient.
View details for DOI 10.14309/crj.0000000000000301
View details for PubMedID 32309495
View details for PubMedCentralID PMC7145162
- Prevalence, risk factors and clinical outcomes of COVID-19 in patients with a history of pancreatitis in Northern California. Gut 2020
- Novel use of endoscopic morcellator to clear large obscuring clot in patient with upper-GI bleed. VideoGIE : an official video journal of the American Society for Gastrointestinal Endoscopy 2020; 5 (2): 58–60
Cathelicidin Mediates a Protective Role of Vitamin D in Ulcerative Colitis and Human Colonic Epithelial Cells.
Inflammatory bowel diseases
Vitamin D plays a protective role in ulcerative colitis (UC) patients through unclear mechanisms. Cathelicidin is an antimicrobial peptide induced by 1,25(OH)D2. Our goal was to evaluate the link between cathelicidin and vitamin D-associated clinical outcomes in UC patients, explore vitamin D induction of cathelicidin in human colon cells, and evaluate the effects of intrarectal human cathelicidin on a murine model of colitis.Serum and colonic cathelicidin levels were measured in UC patients and correlated with clinical and histologic outcomes. Human colon cells were treated with 1,25(OH)2D and production of cathelicidin and cytokines were quantified. Antimicrobial activity against Escherichia coli from cell culture supernatants was measured. Mice were treated with intrarectal cathelicidin, and its effects on DSS colitis and intestinal microbiota were evaluated.In UC patients, serum 25(OH)D positively correlated with serum and colonic cathelicidin. Higher serum cathelicidin is associated with decreased risk of histologic inflammation and clinical relapse but not independent of 25(OH)D or baseline inflammation. The 1,25(OH)2D treatment of colon cells induced cathelicidin and IL-10, repressed TNF-α, and suppressed Escherichia coli growth. This antimicrobial effect was attenuated with siRNA-cathelicidin transfection. Intrarectal cathelicidin reduced the severity of DSS colitis but did not mitigate the impact of colitis on microbial composition.Cathelicidin plays a protective role in 25(OH)D-associated UC histologic outcomes and murine colitis. Cathelicidin is induced by vitamin D in human colonic epithelial cells and promotes antimicrobial activity against E. coli. Our study provides insights into the vitamin D-cathelicidin pathway as a potential therapeutic target.
View details for DOI 10.1093/ibd/izz330
View details for PubMedID 31955203
Systematic review with meta-analysis: association of vitamin D status with clinical outcomes in adult patients with inflammatory bowel disease.
Alimentary pharmacology & therapeutics
Vitamin D deficiency is highly prevalent among patients with IBD, however, data on its association with clinical outcomes are conflicting.To perform a systematic review and meta-analysis to explore the association of low vitamin D status with clinical outcomes in patients with IBD.We searched PubMed, Embase, Scopus and Web of Science from inception to February 2018 for observational studies evaluating the association of low 25(OH)D status on IBD disease activity, mucosal inflammation, clinical relapse and quality of life. Odds ratios (ORs) were pooled and analysed using a random effects model.Twenty-seven studies were eligible for inclusion comprising 8316 IBD patients (3115 ulcerative colitis, 5201 Crohn's disease). Among IBD patients, low 25(OH)D status was associated with increased odds of disease activity (OR 1.53, 95% CI 1.32-1.77, I2 = 0%), mucosal inflammation (OR 1.25, 95% CI 1.06-1.47, I2 = 0%), low quality of life (QOL) scores (OR 1.30, 95% CI 1.06-1.60, I2 = 0%) and future clinical relapse (OR 1.23, 95% CI 1.03-1.47, I2 = 0%). In subgroup analysis, low vitamin D status was associated with Crohn's disease activity (OR 1.66, 95% CI 1.36-2.03, I2 = 0%), mucosal inflammation (OR 1.39, 95% CI 1.03-1.85, I2 = 0%), clinical relapse (OR 1.35, 95% CI 1.14-1.59, I2 = 0%), and low QOL scores (OR 1.25, 95% CI 1.04-1.50, I2 = 0%) and ulcerative colitis disease activity (OR 1.47, 95% CI 1.03-2.09, I2 = 0%) and clinical relapse (OR 1.20, 95% 1.01-1.43, I2 = 0%).Low 25(OH)D status is a biomarker for disease activity and predictor of poor clinical outcomes in IBD patients.
View details for DOI 10.1111/apt.15506
View details for PubMedID 31647134
Managing vitamin D deficiency in inflammatory bowel disease.
2019; 10 (4): 394–400
Management of inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is generally cumbersome for patients and is a massive health-economic burden. In recent years, the immunomodulating effects of vitamin D have gained a huge interest in its possible pathogenic influence on the pathophysiology of IBD. Vitamin D deficiency is frequent among patients with IBD. Several clinical studies have pointed to a critical role for vitamin D in ameliorating disease outcomes. Although causation versus correlation unfortunately remains an overwhelming issue in the illusive chicken versus egg debate regarding vitamin D and IBD, here we summarise the latest knowledge of the immunological effects of vitamin D in IBD and recommend from available evidence that physicians regularly monitor serum 25(OH)D levels in patients with IBD. Moreover, we propose an algorithm for optimising vitamin D status in patients with IBD in clinical practice. Awaiting well-powered controlled clinical trials, we consider vitamin D supplementation to be an affordable and widely accessible therapeutic strategy to ameliorate IBD clinical outcomes.
View details for DOI 10.1136/flgastro-2018-101055
View details for PubMedID 31656565
View details for PubMedCentralID PMC6788352
- Double Threat: Interplay of Celiac Disease with Inflammatory Bowel Disease. Digestive diseases and sciences 2019
Higher serum vitamin D levels are associated with protective serum cytokine profiles in patients with ulcerative colitis.
2018; 103: 38–45
Vitamin D has immune modulating effects on cytokines. Serum vitamin D levels are associated with the risk of relapse in patients with ulcerative colitis (UC), through unknown mechanisms. We tested the hypothesis that this beneficial role of vitamin D on UC is mediated through anti-inflammatory serum cytokine profiles.Serum samples from a prospective cohort of seventy UC patients in clinical remission were collected and baseline histological and endoscopic scores were recorded at enrollment. Clinical relapse events were recorded over the 12-month follow-up period. Serum vitamin D and cytokines levels (IL-6, IL-8, IL-17A, TNF-α, IFN-γ, IL-4, IL-10) were quantified using ELISA. Linear regression was used to determine correlation between vitamin D and cytokine profiles. Logistic regression models were used to determine the association between serum cytokine profiles and baseline histologic mucosal healing and clinical relapse.Higher serum vitamin D levels positively correlated with higher ratios of IL-4 + IL-10/IL-17A + TNF-α (r = 0.37, P < .01), and IL-4 + IL-10/IL-6 + TNF-α (r = 0.32, P < .01). In multivariate analysis, IL-4 + IL-10/IL-17A + TNF-α ratios at baseline were associated with the presence of histologic mucosal healing (O.R. 1.29, 95% CI 1.02-1.62, P = .03). A higher ratio of serum IL-4 + IL-10 to IL-6 + TNF-α was associated with a reduced risk of clinical relapse (O.R. 0.72, 95% CI 0.58-0.89, P = .003), and longer time to relapse (p = .03), over the 12-month follow-up period. This ratio during remission had an AUC of 0.7 in predicting later clinical relapse.Vitamin D is associated with anti-inflammatory serum cytokine profiles. Anti-inflammatory cytokine patterns may mediate the protective effects of higher serum vitamin D levels in patients with ulcerative colitis.
View details for DOI 10.1016/j.cyto.2017.12.023
View details for PubMedID 29324259
View details for PubMedCentralID PMC5808893
Vitamin D in inflammatory bowel disease: more than just a supplement.
Current opinion in gastroenterology
2018; 34 (4): 217–25
The aim of this review is to explore the protective role of vitamin D on the gastrointestinal tract, summarize the epidemiology of vitamin D deficiency in inflammatory bowel disease (IBD), and highlight recent studies examining the impact of low vitamin D and vitamin D supplementation on IBD clinical outcomes.Vitamin D protects the gut barrier by regulating tight junction proteins and inhibiting intestinal apoptosis. Vitamin D enhances innate immunity by inducing antimicrobial peptides and regulates adaptive immunity by promoting anti-inflammatory T cells and cytokines. Vitamin D may also alter the gut microbiota. The prevalence of vitamin D deficiency in IBD is 30-40%. Predictors of vitamin D deficiency in IBD include non-white ethnicity, IBD-related surgery, BMI more than 30, female sex, and pregnancy. Low vitamin D is associated with increased disease activity, inflammation, and clinical relapse. The effect of vitamin D supplementation on IBD clinical outcomes is inconclusive.Vitamin D plays a protective role on gut health. Vitamin D deficiency in IBD is prevalent and associated with poor outcomes. The benefits of vitamin D supplementation in IBD is unclear. Measuring novel vitamin D metabolites and vitamin D absorption in IBD patients may help guide future studies.
View details for DOI 10.1097/MOG.0000000000000449
View details for PubMedID 29762159
- Reply. Clinical gastroenterology and hepatology 2017
Low Serum Vitamin D During Remission Increases Risk of Clinical Relapse in Patients With Ulcerative Colitis.
Clinical gastroenterology and hepatology
2017; 15 (2): 240-246 e1
Vitamin D levels have been associated with disease activity in patients with ulcerative colitis (UC), but it is unclear whether they affect the risk of disease relapse. We sought to determine the association between baseline vitamin D levels during a period of clinical remission and risk of subsequent UC relapse.We performed a physician-blinded prospective study of 70 patients with UC in clinical remission followed up after a surveillance colonoscopy at a tertiary academic medical center. Serum samples were collected at the time of colonoscopy and baseline endoscopic and histologic activity were determined. Levels of 25-hydroxy-vitamin D were measured using an enzyme-linked immunosorbent assay. The primary outcome was rate of clinical relapse, determined over 12 months.The mean baseline vitamin D level was lower among patients with relapse (29.5 ng/mL) than without (50.3 ng/mL) (P = .001). Remission vitamin D level (≤35 ng/mL) was associated with a risk of clinical relapse (odds ratio, 1.25; 95% confidence interval [CI], 1.01-1.56; P = .044) over 12 months, independent of endoscopic or histologic grade at enrollment. A receiver operating characteristic curve of vitamin D levels for the outcome of relapse had an area under the curve of 0.72; and a serum level of 35 ng/mL or less had a sensitivity of 70% (95% CI, 46%-88%) and a specificity of 74% (95% CI 57%-83%) for predicting risk of clinical relapse.Serum levels of vitamin D of 35 ng/mL or less during periods of clinical remission increase the risk of UC relapse. Clinical trials to obtain vitamin D levels higher than this threshold should be considered.
View details for DOI 10.1016/j.cgh.2016.05.035
View details for PubMedID 27266980
View details for PubMedCentralID PMC5136522
Cannabis Abuse Is Increasing and Associated with Increased Emergency Department Utilization in Gastroenterology Patients
DIGESTIVE DISEASES AND SCIENCES
2016; 61 (7): 1844-1852
The role of cannabinoids in gastrointestinal diseases is controversial and of great interest, yet their use in patients has not been critically examined.To determine the prevalence and effects of cannabis abuse on healthcare utilization, as measured by emergency department (ED) visits, in a large, tertiary gastroenterology practice.All patients seen in the gastroenterology clinic at a tertiary care center during a 27-year period (1986-2013) were included in our study to determine the overall prevalence of cannabis abuse. We matched cannabis abusers 1:2 with non-abusing controls to determine the effect of cannabis on ED utilization, our primary outcome. We used multivariate linear regression to adjust for confounders and define the independent effect of cannabis abuse on ED utilization.Our prevalence study cohort included 190,303 GI clinic patients with an overall cannabis abuse prevalence of 0.80 % (1520 patients). From 1986 to 2012, the prevalence of cannabis abuse in this clinic increased by 0.73 % (0.03 %/year) (p < 0.0001). From the 1520 cannabis abusers identified, 467 patients were randomly selected as cases and were matched to 934 controls. From this retrospective cohort, the median ED visits/year for cannabis abusers was 1.88 versus 0.89 for non-abusers (p < 0.0001). After multivariate adjustment, cannabis abuse was associated with a 1.47-fold increase (95 % CI 1.23-1.76, p < 0.0001) in median ED visits/year.Reported cannabis abuse in GI clinic patients is less prevalent than in the adult US population, but is increasing. Cannabis abuse among gastroenterology patients is associated with increased ED visits.
View details for DOI 10.1007/s10620-016-4090-9
View details for Web of Science ID 000379013300013
View details for PubMedID 26935430
Hypercalcemia associated with isolated bone marrow sarcoidosis in a patient with underlying monoclonal gammopathy of undetermined significance: case report and review of literature.
2016; 4: 18-?
Bone marrow sarcoidosis is extremely rare. The association between sarcoidosis and lymphoproliferative disorders has been previously speculated, although the diagnosis of sarcoidosis often precedes any hematological derangements.Here, we report for the first time, a case of a 57-year-old Caucasian woman with a previous diagnosis of monoclonal gammopathy of undetermined significance (MGUS) developing hypercalcemia and renal failure with workup notable for isolated bone marrow sarcoidosis and not multiple myeloma as expected. The patient was successfully managed with prednisone taper therapy with resolution of her hypercalcemia and repeat bone marrow biopsies demonstrating resolving granulomas.Our case illustrates the diagnostic challenges associated with bone marrow sarcoidosis and suggest that chronic immune stimulation in the bone marrow in the setting of MGUS may be associated with the development of localized sarcoidosis. The long term consequences of steroid therapy targeting sarcoidosis in this patient with underlying MGUS remain unknown. Greater surveillance and closer followup is planned in light of the increased risk of malignant transformation of MGUS into multiple myeloma in the setting of bone marrow sarcoidosis.
View details for DOI 10.1186/s40364-016-0072-5
View details for PubMedID 27651903
View details for PubMedCentralID PMC5024499
Hemorrhage from Extra-Antral Gastric Antral Vascular Ectasia in a Patient with Duodenal Heterotopic Gastric Mucosa.
Case reports in gastrointestinal medicine
2016; 2016: 4325302-?
Gastric antral vascular ectasias (GAVE) have been increasingly recognized as an uncommon cause of chronic gastrointestinal bleeding and anemia, although their underlying pathogenesis is not completely well understood. Heterotopic gastric mucosa (HGM) has been reported to occur at various sites along the gastrointestinal tract and although relatively common, it is often asymptomatic. We report a case of a 60-year-old woman with a prior history of GAVE who developed melena and symptomatic anemia during her hospitalization following cardiac catheterization. Initial EGD demonstrated nonbleeding antral GAVE and a newly discovered duodenal mass. Duodenal mass biopsies were ultimately notable for HGM along with histologic features of extra-antral GAVE. The patient required blood transfusions and consequently had a small bowel endoscopy notable for fresh blood in the proximal small bowel. The patient underwent a small bowel push enteroscopy which demonstrated active bleeding of the duodenal mass and overlying oozing GAVE, which was cauterized with Argon-Plasma Coagulation with adequate hemostasis. We present for the first time a novel association between GAVE and HGM. Our case illustrates that extra-antral GAVE may occur with HGM in the duodenum. We explore potential mechanisms by which HGM may be involved in the pathogenesis of GAVE.
View details for PubMedID 27830096
View details for PubMedCentralID PMC5088272
Multistrain influenza protection induced by a nanoparticulate mucosal immunotherapeutic
2011; 4 (2): 197-207
All commercial influenza vaccines elicit antibody responses that protect against seasonal infection, but this approach is limited by the need for annual vaccine reformulation that precludes efficient responses against epidemic and pandemic disease. In this study we describe a novel vaccination approach in which a nanoparticulate, liposome-based agent containing short, highly conserved influenza-derived peptides is delivered to the respiratory tract to elicit potent innate and selective T cell-based adaptive immune responses. Prepared without virus-specific peptides, mucosal immunostimulatory therapeutic (MIT) provided robust, but short-lived, protection against multiple, highly lethal strains of influenza in mice of diverse genetic backgrounds. MIT prepared with three highly conserved epitopes that elicited virus-specific memory T-cell responses but not neutralizing antibodies, termed MITpep, provided equivalent, but more durable, protection relative to MIT. Alveolar macrophages were more important than dendritic cells in determining the protective efficacy of MIT, which induced both canonical and non-canonical antiviral immune pathways. Through activation of airway mucosal innate and highly specific T-cell responses, MIT and MITpep represent novel approaches to antiviral protection that offer the possibility of universal protection against epidemic and pandemic influenza.
View details for DOI 10.1038/mi.2010.50
View details for Web of Science ID 000287302700009
View details for PubMedID 20736998