Purna C. Kashyap's research while affiliated with University of California, Davis and other places

Publications (184)

Article
Full-text available
Gastrointestinal (GI) motility requires coordination among several cell types in the intestinal epithelium and the neuromuscular apparatus. A disruption in GI motility was primarily attributed to disruption of this coordinated effort among different host cells, but recent studies have begun to uncover how the products of gut microbiota can alter GI...
Article
Introduction: Intragastric balloons (IGBs) are a safe and effective treatment for obesity. However, limited knowledge exists on the underlying biological changes with IGB placement. Methods: This single-institution study was part of an adjustable IGB randomized controlled trial. Subjects with obesity were randomized in a 2 is to 1 ratio to 32 we...
Article
Full-text available
While gut microbiome and host gene regulation independently contribute to gastrointestinal disorders, it is unclear how the two may interact to influence host pathophysiology. Here we developed a machine learning-based framework to jointly analyse paired host transcriptomic (n = 208) and gut microbiome (n = 208) profiles from colonic mucosal sample...
Article
Irritable bowel syndrome is a globally prevalent disorder categorized into constipation, diarrhea or mixed (IBS-C, IBD-D, IBS-M) based on the predominant stool form/frequency. While the gut microbiome is recognized as an important factor underlying the pathophysiology of IBS, the specific mechanisms remain an area of active investigation. In our re...
Article
Full-text available
Intestinal proteases mediate digestion and immune signalling, while increased gut proteolytic activity disrupts the intestinal barrier and generates visceral hypersensitivity, which is common in irritable bowel syndrome (IBS). However, the mechanisms controlling protease function are unclear. Here we show that members of the gut microbiota suppress...
Article
Full-text available
Background: Primary sclerosing cholangitis (PSC) is a major risk factor for cholangiocarcinoma (CCA). We investigated biliary and fecal microbiota to determine whether specific microbes in the bile or stool are associated with PSC or CCA. Methods: Bile was obtained from 32 patients with PSC, 23 with CCA with PSC, 26 with CCA without PSC, and 17...
Article
Full-text available
Microbial communities provide protection to their hosts by resisting pathogenic invasion. Microbial residents of a host often exclude subsequent colonizers, but this protection is not well understood. The Enterococcus faecalis plasmid pCF10, whose conjugative transfer functions are induced by a peptide pheromone, efficiently transfers in the intest...
Article
Full-text available
The enteric pathogen Clostridioides difficile ( Cd ) is responsible for a toxin-mediated infection that causes more than 200,000 recorded hospitalizations and 13,000 deaths in the United States every year ¹ . However, Cd can colonize the gut in the absence of disease symptoms. Prevalence of asymptomatic colonization by toxigenic Cd in healthy popul...
Article
Full-text available
Irritable bowel syndrome (IBS) results from disordered brain–gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 5...
Article
Full-text available
Recent studies of the human microbiome have offered new insights into how the microbiome can impact cancer development and treatment. Specifically, in pancreatic ductal adenocarcinoma (PDAC), the microbiota has been shown to modulate PDAC risk, contribute to tumorigenesis, impact the tumor microenvironment, and alter treatment response. These findi...
Article
Variability in disease presentation, progression and treatment response has been a central challenge in medicine. Although variability in host factors and genetics are important, it has become evident that the gut microbiome, with its vast genetic and metabolic diversity, must be considered in moving towards individualized treatment. In this Review...
Article
Background and aims The gut virome includes eukaryotic viruses and bacteriophages that can shape the gut bacterial community and elicit host responses. The virome may be implicated in diseases such as irritable bowel syndrome (IBS), where gut bacteria play an important role in pathogenesis. Herein we provide a comprehensive and longitudinal charact...
Conference Paper
p>The role of maternal microbiome transmitted at birth in cancer control is poorly understood. We have developed the first germfree B6 mouse model of breast cancer to investigate the role of the maternal microbiome in controlling oncogenic/metastatic frequencies of pro-oncogenic mammary cells. In this model, a DNA barcoded, primitive normal mouse m...
Preprint
Full-text available
While the gut microbiome and host gene regulation separately contribute to gastrointestinal disorders, it is unclear how the two may interact to influence host pathophysiology. Here, we developed a machine learning-based framework to jointly analyze host transcriptomic and microbiome profiles from 416 colonic mucosal samples of patients with colore...
Article
Full-text available
Parkinson’s disease (PD) is a common neurodegenerative disorder characterized primarily by motor and non-motor gastrointestinal (GI) deficits. GI symptoms’ including compromised intestinal barrier function often accompanies altered gut microbiota composition and motor deficits in PD. Therefore, in this study, we set to investigate the role of gut m...
Article
Full-text available
Recent studies emphasize the role of microbial metabolites in regulating gastrointestinal (GI) physiology through activation of host receptors, highlighting the potential for inter-kingdom signaling in treating GI disorders. In this study, we show that tryptamine, a tryptophan-derived bacterial metabolite, stimulates mucus release from goblet cells...
Article
The increasing incidence of primary and recurring Clostridioides difficile infections (CDI), which evade current treatment strategies, reflects the changing biology of C difficile. Here, we describe a putative plasmid-mediated mechanism potentially driving decreased sensitivity of C difficile to vancomycin treatment. We identified a broad host rang...
Article
There have been numerous human studies reporting associations between the intestinal microbiome and functional gastrointestinal disorders (FGIDs), and independently animal studies have explored microbiome-driven mechanisms underlying FGIDs. However, there is often a disconnect between human and animal studies, which hampers translation of microbiom...
Article
p>(Cell 182, 1460–1473.e1–e17; September 17, 2020) In preparing the final version of this article, we overlooked some errors and we apologize for these shortcomings. None of these errors involved our data analyses or affected the conclusions presented in the manuscript. These errors have now been corrected online. 1. In Figure 2B the y axis should...
Article
Full-text available
Microbiota-accessible carbohydrates (MACs) are powerful modulators of microbiota composition and function. These substrates are often derived from diet, such as complex polysaccharides from plants or human milk oligosaccharides (HMOs) during breastfeeding. Host-derived mucus glycans on gut-secreted mucin proteins serve as a continuous endogenous so...
Article
Full-text available
Stress is a known trigger for flares of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS); however, this process is not well understood. Here, we find that restraint stress in mice leads to signs of diarrhea, fecal dysbiosis, and a barrier defect via the opening of goblet-cell associated passages. Notably, stress increases host im...
Article
Full-text available
Overweight and obesity are global health problems that contribute to the rising prevalence of non-communicable diseases, such as type 2 diabetes, heart disease, and certain cancers. The World Health Organization recognizes obesity as a primarily diet-induced, preventable condition, yet losing weight or keeping weight loss permanent is a universal c...
Article
The microbiome plays a major role in human physiology by influencing obesity, inducing inflammation, and impacting cancer therapies. During the 60th Annual Meeting of the Society of the Alimentary Tract (SSAT) at the State-of-the-Art Conference, experts in the field discussed the influence of the microbiome. This paper is a summary of the influence...
Article
The gut microbiome has been implicated in multiple human chronic gastrointestinal (GI) disorders. Determining its mechanistic role in disease has been difficult due to apparent disconnects between animal and human studies and lack of an integrated multi-omics view of disease-specific physiological changes. We integrated longitudinal multi-omics dat...
Article
Parkinson's diseases (PD) is a common neurodegenerative disorder characterized by motor and gastrointestinal (GI) deficits. Despite its prevalence, the pathophysiology of PD is not well understood. Recent studies highlight the role of gut microbiota in neurological disorders. In this review, we summarize the potential role of gut microbiota in the...
Article
Full-text available
The early stages of the metagenomics era produced countless observational studies linking various human diseases to alterations in the gut microbiota. Only recently have we begun to decipher the causal roles that gut microbes play in many of these conditions. Despite an incomplete understanding of how gut microbes influence pathophysiology, clinica...
Preprint
Full-text available
Microbiota-accessible carbohydrates (MACs) are powerful modulators of microbiota composition and function. These substrates are often derived from diet, such as complex polysaccharides from plants or human milk oligosaccharides (HMOs) during breastfeeding. Host-derived mucus glycans on gut-secreted mucin proteins may serve as a continuous endogenou...
Article
Background and aims We aimed to compare the effectiveness of single- vs multiple-strain probiotics in a network meta-analysis of randomized trials. Methods We searched MEDLINE, EMBASE, Science Citation Index Expanded, CINAHL, Scopus, Cochrane CENTRAL, BIOSIS Previews, and Google Scholar through January 1, 2019 for studies of single-strain and mult...
Preprint
Here we report the first method for rapid on-site monitoring of germfree C57BL/6 mice colonized with feces from conventionally raised mice. The method, named levo in fimo test, readily distinguishes feces from germfree mice and conventionalized germfree mice based on its properties to float or sink in Trumps fixative solution. We validated the test...
Article
Full-text available
Background The gut microbiome harbors trillions of bacteria that play a major role in dietary nutrient extraction and host metabolism. Metabolic diseases such as obesity and diabetes are associated with shifts in microbiome composition and have been on the rise in Westernized or highly industrialized countries. At the same time, Westernized diets l...
Article
Background Poor air quality is increasingly associated with several gastrointestinal diseases suggesting a possible association between air quality and the human gut microbiome. However, details on this remain largely unexplored as current available research is scarce. The aim of this comprehensive rigorous review was to summarize the existing repo...
Article
Background: High-fat diet, microbial alterations and lipopolysaccharide (LPS) are thought to cause enteric diabetic neuropathy and intestinal dysmotility. However, the role of the gut microbiota, lipoteichoic acid (LTA) from Gram-positive bacteria and short-chain fatty acids (SCFAs) in the development of diabetic enteric neuropathy and intestinal...
Article
Background: Current approaches in tracking Clostridioides difficile infection (CDI) and individualizing patient management are incompletely defined. Methods: We recruited 468 subjects with C. difficile infection at Mayo Clinic Rochester between May and December 2016 and performed whole genome sequencing (WGS) on C. difficile isolates from 397. W...
Article
Full-text available
Introduction: Up to 15% of Campylobacter jejuni enteritis patients may develop post-infection irritable bowel syndrome (PI-IBS). The mechanisms for PI-IBS development remain unclear. A subset of PI-IBS patients (~40%) have elevated proteolytic activity (PA) in their stool correlating with looser and more frequent bowel movements1. Aims & Methods: O...
Article
Full-text available
Abstract Abnormalities in the gut microbiome are associated with suppressed Th2 response (Belizario et al., 2018 Mediators Inflamm. 2018:2037838) and predisposition to atopic disease such as asthma and eczema. We investigated if this applies to eosinophilic esophagitis (EoE). Stool bacterial DNA was extracted and followed by 16S rRNA amplification...
Article
Full-text available
Background: Controlled glycemic concentrations are associated with a lower risk of conditions such as cardiovascular disease and diabetes. Models commonly used to guide interventions to control the glycemic response to food have low efficacy, with recent clinical guidelines arguing for the use of personalized approaches. Objective: We tested the...
Article
Full-text available
Small intestinal bacterial overgrowth (SIBO) has been implicated in symptoms associated with functional gastrointestinal disorders (FGIDs), though mechanisms remain poorly defined and treatment involves non-specific antibiotics. Here we show that SIBO based on duodenal aspirate culture reflects an overgrowth of anaerobes, does not correspond with p...
Article
Objective: The intestinal lumen contains several proteases. Our aim was to determine the role of faecal proteases in mediating barrier dysfunction and symptoms in IBS. Design: 39 patients with IBS and 25 healthy volunteers completed questionnaires, assessments of in vivo permeability, ex vivo colonic barrier function in Ussing chambers, tight junc...
Article
Full-text available
Importance: Emerging evidence suggests that postprandial glycemic responses (PPGRs) to food may be influenced by and predicted according to characteristics unique to each individual, including anthropometric and microbiome variables. Interindividual diversity in PPGRs to food requires a personalized approach for the maintenance of healthy glycemic...
Article
Many US immigrant populations develop metabolic diseases post immigration, but the causes are not well understood. Although the microbiome plays a role in metabolic disease, there have been no studies measuring the effects of US immigration on the gut microbiome. We collected stool, dietary recalls, and anthropometrics from 514 Hmong and Karen indi...
Article
Background Inflammatory bowel diseases (IBDs) are a group of heterogeneous inflammatory conditions affecting the gastrointestinal tract. Although there is considerable evidence linking the gut microbiota to intestinal inflammation, there is limited knowledge on its potential role in the development of extraintestinal manifestations of IBD. Methods...
Article
The rising incidence of obesity requires the reevaluation of our current therapeutic strategies to optimize patient outcomes. The objective of this study was to determine whether compositional and functional characteristics of the gut microbiota in adults predict responses to a comprehensive lifestyle intervention program in overweight and obese ad...
Article
The importance of gut microbiota in gastrointestinal (GI) physiology was well described, but our ability to study gut microbial ecosystems in their entirety was limited by culture-based methods prior to the sequencing revolution. The advent of high-throughput sequencing opened new avenues, allowing us to study gut microbial communities as an aggreg...
Article
Full-text available
Intestinal barrier function and microbiota are integrally related and play critical roles in maintenance of host physiology. Sex is a key biologic variable for several disorders. Our aim was to determine sex-based differences in response to perturbation and subsequent recovery of intestinal barrier function and microbiota in healthy humans. Twenty-...
Article
Tryptamine, a tryptophan-derived monoamine similar to 5-hydroxytryptamine (5-HT), is produced by gut bacteria and is abundant in human and rodent feces. However, the physiologic effect of tryptamine in the gastrointestinal (GI) tract remains unknown. Here, we show that the biological effects of tryptamine are mediated through the 5-HT4 receptor (5-...
Article
Full-text available
We show that a citizen science, self-selected cohort shipping samples through the mail at room temperature recaptures many known microbiome results from clinically collected cohorts and reveals new ones. Of particular interest is integrating n = 1 study data with the population data, showing that the extent of microbiome change after events such as...