Kyle Bittinger

Kyle Bittinger
University of Pennsylvania | UP · Department of Microbiology (Medicine)

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305
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Publications

Publications (305)
Article
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Complications of short bowel syndrome (SBS) include malabsorption and bacterial overgrowth, requiring prolonged dependence on parenteral nutrition (PN). We hypothesized that the intolerance of whole food in some SBS patients might be due to the effect of dietary fiber on the gut microbiome. Shotgun metagenomic sequencing and targeted metabolomics w...
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The baseline composition of T cells directly impacts later response to pathogens, but the complexity of precursor states remains poorly defined. Here, we examined the baseline state of SARS-CoV-2-specific T cells in unexposed individuals. SARS-CoV-2-specific CD4 ⁺ T cells were identified in pre-pandemic blood samples by class II peptide-MHC tetrame...
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Environmental pH is a critical parameter for maintenance of the gut microbiota. Here, the impact of pH on the gut microbiota luminal and mucosal community structure and short chain fatty acid (SCFA) production was evaluated in vitro, and data compiled to reveal a donor-independent response to an increase or decrease in environmental pH. The results...
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This proof-of-principle study analyzed fecal samples from 30 infants who participated in a randomized controlled trial on the effects of the macronutrient composition of infant formula on growth and energy balance. In that study, infants randomized to be fed cow milk formula (CMF) had faster weight-gain velocity during the first 4 months and higher...
Article
Background & Aims Perianal fistulizing disease can affect up to 25% of patients with Crohn’s disease (CD) and lead to significant morbidity. While the role of the gut microbiota in inflammatory bowel disease (IBD) has been increasingly recognized, its role in fistula development has scarcely been studied. Here, we aimed to define the microbial sign...
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Biofilm community development has been established as a sequential process starting from the attachment of single cells on a surface. However, microorganisms are often found as aggregates in the environment and in biological fluids. Here, we conduct a comprehensive analysis of the native structure and composition of aggregated microbial assemblages...
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The primary aim of this review was to systematically evaluate the literature regarding the effect of pre-, pro-, or synbiotic supplementation in infant formula on the gastrointestinal microbiota. The Cochrane methodology for systematic reviews of randomized controlled trials (RCTs) was employed. Five databases were searched and 32 RCTs (2010–2021)...
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Background: Pediatric immune thrombocytopenia purpura (ITP) is the most common cause of autoimmune cytopenias in children and results in autoimmune destruction of platelets, leading to significantly decreased circulating platelets, increased bleeding risk and fatigue. The underlying mechanism of action is thought to be auto-antibody driven, though...
Preprint
Recently, several molecular imaging strategies have developed to image bacterial infections in humans. Nuclear approaches, specifically positron emission tomography (PET), affords sensitive detection and the ability to non-invasively locate infections deep within the body. Two key radiotracer classes have arisen: metabolic approaches targeting bact...
Preprint
Mammals produce large quantities of mucosal and systemic antibodies that maintain the intestinal barrier, shape the intestinal microbiome and promote lifelong mutualism with commensal microbes. Here, we developed an integrated host-commensal approach combining microbial flow cytometry and 16s rRNA gene sequencing to define the core microbes that in...
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COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of the respiratory tract, results in highly variable outcomes ranging from minimal illness to death, but the reasons for this are not well understood. We investigated the respiratory tract bacterial microbiome and small commensal DNA viruses in hospitalized C...
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Gut dysbiosis is a common feature associated with the chronic inflammation of HIV infection. Toward understanding the interplay of chronic treated HIV infection, dysbiosis, and systemic inflammation, we investigated longitudinal fecal microbiome changes and plasma inflammatory markers in the nonhuman primate model. Following simian immunodeficiency...
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A cross sectional study of 41 children ages 4-17 years with alopecia areata (AA) and 41 of their siblings without AA was conducted. Fifty-one percent had severity of alopecia tool scores in the 0-25% range, 12% between 26-49%, 36% between 75-100%. The fecal microbiome was characterized using shotgun metagenomic sequencing. A comparison of alpha and...
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Introduction Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver disease that accompanies obesity and the metabolic syndrome. Excess fructose consumption can initiate or exacerbate NAFLD in part due to a consequence of impaired hepatic fructose metabolism. Preclinical data emphasized that fructose-induced altered gut m...
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Inhibitors of mPges-1 are in the early phase of clinical development. Deletion of mPges-1 in mice confers analgesia, restrains atherogenesis and fails to accelerate thrombogenesis, while suppressing PGE2, but increasing biosynthesis of PGI2. In Ldlr-/- mice, this last effect represents the dominant mechanism by which mPges-1 deletion restrains thro...
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Objectives To identify dietary patterns in 12-month-old African American infants and investigate their association with change in infant BMI z-score (BMIz) from 12 to 24 months. Methods The prospective longitudinal Infant Growth and Microbiome Study (IGram) enrolled African American women in their 3rd trimester of pregnancy who had a pre-pregnancy...
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Leg ulcers are estimated to occur in 1%–10% of North American patients with sickle cell disease (SCD). Their pathophysiology remains poorly defined, but as with other chronic wounds, it is hypothesised that the microbial milieu, or microbiome, contributes to their healing and clinical outcomes. This study utilises 16S ribosomal RNA (rRNA) gene sequ...
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The present experiments determined the effects of the narrow-spectrum antibiotic vancomycin on inflammatory pain-stimulated and pain-depressed behaviors in rats. Persistent inflammatory pain was modeled using dilute formalin (0.5%). Two weeks of oral vancomycin administered in drinking water attenuated Phase II formalin pain-stimulated behavior, an...
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Background & Aims This study compared the effectiveness of the Specific Carbohydrate Diet (SCD) to the Mediterranean Diet (MD) as treatment for Crohn’s disease (CD) with mild to moderate symptoms. Methods Adult patients with CD and with mild-moderate symptoms were randomly assigned 1:1 to consume the MD or SCD for 12 weeks. For the first 6-weeks,...
Preprint
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Rationale: Viral infection of the respiratory tract can be associated with propagating effects on the airway microbiome, and microbiome dysbiosis may influence viral disease. Objective: To define the respiratory tract microbiome in COVID-19 and relationship disease severity, systemic immunologic features, and outcomes. Methods and Measurements: We...
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The importance of the gut microbiota in human health and disease progression makes it a target for research in both the biomedical and nutritional fields. To date, a number of in vitro systems have been designed to recapitulate the gut microbiota of the colon ranging in complexity from the application of a single vessel to cultivate the community i...
Preprint
Allergic skin diseases are common, but basal roles for type 2 immunity in cutaneous homeostasis are incompletely understood. Here, we show that skin group 2 innate lymphoid cells (ILC2s) are the predominant resident cells that secretes IL-13, which attenuates epithelial cell proliferation during anagen throughout the hair follicle (HF), including i...
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Objectives:. The intestinal microbiome can modulate immune function through production of microbial-derived short-chain fatty acids. We explored whether intestinal dysbiosis in children with sepsis leads to changes in microbial-derived short-chain fatty acids in plasma and stool that are associated with immunometabolic dysfunction in peripheral blo...
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Objective Little is known about temporal changes in nasal bacteria in granulomatosis with polyangiitis (GPA). We examined longitudinal changes in the nasal microbiome in association with relapse in GPA patients. Methods Bacterial 16S gene sequencing was performed on nasal swabs of 19 patients with GPA followed longitudinally for a total of 78 visi...
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Fecal microbiota transplantation (FMT) is a successful therapeutic strategy for treating recurrent Clostridioides difficile infection. Despite remarkable efficacy, implementation of FMT therapy is limited and the mechanism of action remains poorly understood. Here, we demonstrate a critical role for the immune system in supporting FMT using a murin...
Article
Introduction The microbiome has been suggested to play an important role in the pathogenesis and progression of Crohn’s disease (CD) with the components of a Western diet, in turn, potentially altering the gut microbiome. We conducted an observational study comparing dietary influences on the gut microbiota in children with active or quiescent CD w...
Article
Gut microbiota metabolites may be important for host health, yet few studies investigate the correlation between human gut microbiome and production of fecal metabolites and their impact on the plasma metabolome. Since gut microbiota metabolites are influenced by diet, we performed a longitudinal analysis of the impact of three divergent diets, veg...
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Objectives: The objective of this study was to characterize gut microbiome profiles of infants with congenital hyperinsulinism (HI) who underwent near-total or partial pancreatectomy for hypoglycemia management, as compared with healthy controls. Methods: A prospective observational cohort study was performed. Subjects were infants (0-6 months)...
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Most studies examining correlations between the gut microbiota and disease states focus on fecal samples due to ease of collection, yet there are distinct differences when compared to samples collected from the colonic mucosa. Although fecal microbiota has been reported to be altered in cirrhosis, correlation with mucosal microbiota characterized v...
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Mycobacterium chelonae is a rapidly growing nontuberculous mycobacterium that is a common cause of nosocomial infections. Here we describe investigation of a possible nosocomial transmission of M . chelonae at the Hospital of the University of Pennsylvania (HUP). M . chelonae strains with similar high-level antibiotic resistance patterns were isola...
Article
Children with inflammatory bowel diseases (IBD) are particularly vulnerable to infection with Clostridioides difficile (CDI). IBD and IBD + CDI have overlapping symptoms but respond to distinctive treatments, highlighting the need for diagnostic biomarkers. Here, we studied pediatric patients with IBD and IBD + CDI, comparing longitudinal data on t...
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Background: No studies to date have comprehensively assessed the changes occurring in the subgingival microbiome of young periodontal patients treated by means of mechanical and antibiotic therapy. Thus, this study aimed to use Next-Generation Sequencing to evaluate the subgingival microbial composition of young patients with severe periodontitis...
Preprint
Full-text available
Mycobacterium chelonae is a rapidly growing nontuberculous mycobacterium that is a common cause of nosocomial infections. Here we describe investigation of a possible nosocomial transmission of M. chelonae at the Hospital of the University of Pennsylvania (HUP). M. chelonae strains with similar high-level antibiotic resistance patterns were isolate...
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The recent ban of the antimicrobial compound triclosan from use in consumer soaps followed research that showcased the risk it poses to the environment and to human health. Triclosan has been found in human plasma, urine and milk, demonstrating that it is present in human tissues. Previous work has also demonstrated that consumption of triclosan di...
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Initial microbial colonization and later succession in the gut of human infants are linked to health and disease later in life. The timing of the appearance of the first gut microbiome, and the consequences for the early life metabolome, are just starting to be defined. Here, we evaluated the gut microbiome, proteome and metabolome in 88 African-Am...
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OBJECTIVES/GOALS: The current proposal seeks to investigate the effect of early life antibiotic use in the development of functional gastrointestinal (GI) disorders. We propose that infants exposed to antibiotics will present with gut microbial dysbiosis, changes in fecal bile acid concentrations and develop more GI symptoms compared to unexposed c...
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The gut of healthy human neonates is usually devoid of viruses at birth, but quickly becomes colonized, which—in some cases—leads to gastrointestinal disorders1–4. Here we show that the assembly of the viral community in neonates takes place in distinct steps. Fluorescent staining of virus-like particles purified from infant meconium or early stool...
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Cavernous angiomas (CA) are common vascular anomalies causing brain hemorrhage. Based on mouse studies, roles of gram-negative bacteria and altered intestinal homeostasis have been implicated in CA pathogenesis, and pilot study had suggested potential microbiome differences between non-CA and CA individuals based on 16S rRNA gene sequencing. We her...
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Background: African populations provide a unique opportunity to interrogate host-microbe co-evolution and its impact on adaptive phenotypes due to their genomic, phenotypic, and cultural diversity. We integrate gut microbiome 16S rRNA amplicon and shotgun metagenomic sequence data with quantification of pathogen burden and measures of immune param...
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Background and Aims Dysbiosis of the gut microbiota is a well-known correlate of the pathogenesis of inflammatory bowel disease [IBD]. However, few studies have examined the microbiome in very early-onset [VEO] IBD, which is defined as onset of IBD before 6 years of age. Here we focus on the viral portion of the microbiome—the virome—to assess poss...
Article
Background: The relationship between the composition and function of gut microbial communities and early-onset calcium oxalate kidney stone disease is unknown. Methods: We conducted a case-control study of 88 individuals aged 4-18 years, which included 44 individuals with kidney stones containing ≥50% calcium oxalate and 44 controls matched for...
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Chronic exposure to stress is associated with increased incidence of depression, generalized anxiety, and PTSD. However, stress induces vulnerability to such disorders only in a sub-population of individuals, as others remain resilient. Inflammation has emerged as a putative mechanism for promoting stress vulnerability. Using a rodent model of soci...
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Segmented filamentous bacteria (SFB) are well appreciated for eliciting Th17 cell immune responses. Here, we report the genome sequence of a murine isolate of SFB, which confers strong protection against rotavirus infection independent of acquired immunity.
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An emerging paradigm suggests that gut glycosylation is a key force in maintaining the homeostatic relationship between the gut and its microbiota. Nevertheless, it is unclear how gut glycosylation contributes to the HIV-associated microbial translocation and inflammation that persist despite viral suppression and contribute to the development of s...
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Secondary bile acids (SBAs) are derived from primary bile acids (PBAs) in a process reliant on biosynthetic capabilities possessed by few microbes. To evaluate the role of BAs in intestinal inflammation, we performed metabolomic, microbiome, metagenomic, and transcriptomic profiling of stool from ileal pouches (surgically created resevoirs) in cole...
Article
Leaf extracts of Stevia rebaudiana , composed of more than ten steviol glycosides (SGs), are used as non-nutritive, table sugar (sucrose) alternatives due to their high level of sweetness and low caloric impact. They are often combined with the sugar alcohol erythritol to increase volume and reduce aftertaste. Little is known of the impact of sugar...
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Alterations in gut microbiota impact the pathophysiology of several diseases, including cancer. Radiotherapy (RT), an established curative and palliative cancer treatment, exerts potent immune modulatory effects, inducing tumor-associated antigen (TAA) cross-priming with antitumor CD8+ T cell elicitation and abscopal effects. We tested whether the...
Article
Cerebral cavernous malformation (CCM) is a genetic, cerebrovascular disease. Familial CCM is caused by genetic mutations in KRIT1 , CCM2 , or PDCD10 . Disease onset is earlier and more severe in individuals with PDCD10 mutations. Recent studies have shown that lesions arise from excess mitogen-activated protein kinase kinase kinase 3 (MEKK3) signal...
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The colon gut microbiota is responsible for complex chemical conversions of nutrients and subsequent release of metabolites that have diverse biological consequences. However, information on the metabolic dynamics that occur longitudinally through the colon is limited. Here, gas and liquid chromatography coupled with mass spectrometry were applied...
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Rotavirus (RV) encounters intestinal epithelial cells amidst diverse microbiota, opening possibilities of microbes influencing RV infection. Although RV clearance typically requires adaptive immunity, we unintentionally generated RV-resistant immunodeficient mice, which, we hypothesized, reflected select microbes protecting against RV. Accordingly,...
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An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Acute flaccid myelitis (AFM) is a polio-like disease that results in paralysis in previously healthy persons. Although the definitive cause of AFM remains unconfirmed, enterovirus D68 (EV-D68) is suspected based on 2014 data demonstrating an increase in AFM cases concomitant with an EV-D68 outbreak. We examined the prevalence in children and the mo...
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Rationale: The oropharyngeal microbiome is a primary source of lung microbiota, contributes to lower respiratory infection, and is also a driver of oral health.Objectives: We sought to understand oropharyngeal microbial communities in advanced lung disease, community dynamics after lung transplantation, and ecological features of dysbiosis.Methods:...
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Changes in the gut microbiota and the mitochondrial genome are both linked with the development of disease. To investigate why, we examined the gut microbiota of mice harboring various mutations in genes that alter mitochondrial function. These studies revealed that mitochondrial genetic variations altered the composition of the gut microbiota comm...