scholarly journals Giardiaalters commensal microbial diversity throughout the murine gut

2016 ◽  
Author(s):  
NR Barash ◽  
JG Maloney ◽  
SM Singer ◽  
SC Dawson
Keyword(s):  
Small Intestine ◽  
Diarrheal Disease ◽  
Commensal Microbiota ◽  
Microbial Dysbiosis ◽  
Proximal Small Intestine ◽  
Culture Independent ◽  
Duration Of Infection ◽  
The Impact ◽  
Aerobic And Anaerobic ◽  
Entire Gastrointestinal Tract

ABSTRACTGiardia lambliais the most frequently identified protozoan cause of intestinal infection. Over one billion people are estimated to have acute or chronic giardiasis, with infection rates approaching 90% in endemic areas. Despite its significance in global health, the mechanisms of pathogenesis associated with giardiasis remain unclear as the parasite neither produces a known toxin nor induces a robust inflammatory response.Giardiacolonization and proliferation in the small intestine of the host may, however, disrupt the ecological homeostasis of gastrointestinal commensal microbes and contribute to diarrheal disease associated with giardiasis. To evaluate the impact ofGiardiainfection on the host microbiota, we use culture-independent methods to quantify shifts in the diversity of commensal microbes throughout the entire gastrointestinal tract in mice infected withGiardia. We discovered thatGiardia’scolonization of the small intestine causes a systemic dysbiosis of aerobic and anaerobic bacterial taxa. Specifically, giardiasis is typified by both expansions in aerobicProteobacteriaand decreases in anaerobicFirmicutesandMelainabacteriain the murine foregut and hindgut. Based on these shifts, we created a quantitative index of murineGiardia-induced microbial dysbiosis. This index increased at all gut regions during the duration of infection, including both the proximal small intestine and the colon. Thus giardiasis could be an ecological disease, and the observed dysbiosis may be mediated directly via the parasite’s unique anaerobic fermentative metabolism or indirectly via parasite induction of gut inflammation. This systemic alteration of murine gut commensal diversity may be the cause or the consequence of inflammatory and metabolic changes throughout the gut. Shifts in the commensal microbiota may explain observed variation in giardiasis between hosts with respect to host pathology, degree of parasite colonization, infection initiation, and eventual clearance.

scholarly journals Giardia Alters Commensal Microbial Diversity throughout the Murine Gut

2017 ◽  
Vol 85 (6) ◽  
Author(s):  
N. R. Barash ◽  
J. G. Maloney ◽  
S. M. Singer ◽  
S. C. Dawson
Keyword(s):  
Small Intestine ◽  
Diarrheal Disease ◽  
Content Type ◽  
Commensal Microbiota ◽  
Microbial Dysbiosis ◽  
Proximal Small Intestine ◽  
Culture Independent ◽  
Duration Of Infection ◽  
The Impact ◽  
Aerobic And Anaerobic

ABSTRACT Giardia lamblia is the most frequently identified protozoan cause of intestinal infection. Over 200 million people are estimated to have acute or chronic giardiasis, with infection rates approaching 90% in areas where Giardia is endemic. Despite its significance in global health, the mechanisms of pathogenesis associated with giardiasis remain unclear, as the parasite neither produces a known toxin nor induces a robust inflammatory response. Giardia colonization and proliferation in the small intestine of the host may, however, disrupt the ecological homeostasis of gastrointestinal commensal microbes and contribute to diarrheal disease associated with giardiasis. To evaluate the impact of Giardia infection on the host microbiota, we used culture-independent methods to quantify shifts in the diversity of commensal microbes throughout the gastrointestinal tract in mice infected with Giardia. We discovered that Giardia's colonization of the small intestine causes a systemic dysbiosis of aerobic and anaerobic commensal bacteria. Specifically, Giardia colonization is typified by both expansions in aerobic Proteobacteria and decreases in anaerobic Firmicutes and Melainabacteria in the murine foregut and hindgut. Based on these shifts, we created a quantitative index of murine Giardia-induced microbial dysbiosis. This index increased at all gut regions during the duration of infection, including both the proximal small intestine and the colon. Giardiasis could be an ecological disease, and the observed dysbiosis may be mediated directly via the parasite's unique anaerobic fermentative metabolism or indirectly via parasite induction of gut inflammation. This systemic alteration of murine gut commensal diversity may be the cause or the consequence of inflammatory and metabolic changes throughout the gut. Shifts in the commensal microbiota may explain observed variations in giardiasis between hosts with respect to host pathology, degree of parasite colonization, infection initiation, and eventual clearance.

scholarly journals Giardia colonizes and encysts in high density foci in the murine small intestine

2016 ◽  
Author(s):  
NR Barash ◽  
C Nosala ◽  
JK Pham ◽  
SG Mclnally ◽  
S Gourguechon ◽  
...  
Keyword(s):  
Small Intestine ◽  
Gastrointestinal Tract ◽  
Diarrheal Disease ◽  
Laboratory Culture ◽  
High Density ◽  
Infection Dynamics ◽  
Proximal Small Intestine ◽  
Entire Duration ◽  
Duration Of Infection

AbstractGiardiais a highly prevalent, yet understudied protistan parasite causing diarrheal disease worldwide. Hosts ingestGiardiacysts from contaminated sources. In the gastrointestinal tract, cysts excyst to become motile trophozoites, colonizing and attaching to the gut epithelium. Trophozoites later differentiate into infectious cysts that are excreted and contaminate the environment. Due to the limited accessibility of the gut, the temporospatial dynamics of giardiasis in the host is largely inferred from laboratory culture and thus may not mirrorGiardiaphysiology in the host. Here we have developed bioluminescent imaging (BLI) to directly interrogate and quantify thein vivotemporospatial dynamics of giardiasis, thereby providing an improved murine model to evaluate anti-Giardiadrugs. Using BLI, we determined that parasites primarily colonize the proximal small intestine non-uniformly in high-density foci. By imaging encystation-specific bioreporters, we show that encystation initiates shortly after inoculation and continues throughout the entire duration of infection. Encystation also initiates in high-density foci in the proximal small intestine, and high-density laboratory cultures of parasites are also stimulated to encyst. This work overturns the assumption that parasites encyst later during infection as they are dislodged and travel through the colon. We suggest that these high-density regions of parasite colonization likely result in localized pathology to the epithelium, and encystation occurs when trophozoites reach a threshold density due to local nutrient depletion. This more accurate visualization of giardiasis redefines the dynamics ofin vivo Giardialife cycle, paving the way for future mechanistic studies of density-dependent parasitic processes in the host.SignificanceGiardiais a single-celled parasite causing both acute and chronic diarrheal disease in over one billion people worldwide. Due to limited access to the site of infection in the gastrointestinal tract, our understanding of the dynamics ofGiardiainfections in the host has remained limited, and largely inferred from laboratory culture. To better understand giardiasis in the host, we developed imaging methods to quantifyGiardiaexpressing bioluminescent physiological reporters in live mice. We discovered that parasites primarily colonize and encyst in the proximal small intestine in discrete, high-density foci. Furthermore, this work provides evidence of a parasite density-based threshold for the differentiation ofGiardiainto cysts in the host. These findings overturn existing paradigms of giardiasis infection dynamics in the host.

scholarly journals Bile Acids and Bicarbonate Inversely Regulate Intracellular Cyclic di-GMP in Vibrio cholerae

2014 ◽  
Vol 82 (7) ◽  
pp. 3002-3014 ◽  
Author(s):  
Benjamin J. Koestler ◽  
Christopher M. Waters
Keyword(s):  
Small Intestine ◽  
Bile Acids ◽  
Vibrio Cholerae ◽  
Diarrheal Disease ◽  
Intracellular Concentration ◽  
Intestinal Epithelial ◽  
Content Type ◽  
Proximal Small Intestine ◽  
Ph Buffer ◽  
Messenger Molecule

ABSTRACTVibrio choleraeis a Gram-negative bacterium that persists in aquatic reservoirs and causes the diarrheal disease cholera upon entry into a human host.V. choleraeemploys the second messenger molecule 3′,5′-cyclic diguanylic acid (c-di-GMP) to transition between these two distinct lifestyles. c-di-GMP is synthesized by diguanylate cyclase (DGC) enzymes and hydrolyzed by phosphodiesterase (PDE) enzymes. Bacteria typically encode many different DGCs and PDEs within their genomes. Presumably, each enzyme senses and responds to cognate environmental cues by alteration of enzymatic activity. c-di-GMP represses the expression of virulence factors inV. cholerae, and it is predicted that the intracellular concentration of c-di-GMP is low during infection. Contrary to this model, we found that bile acids, a prevalent constituent of the human proximal small intestine, increase intracellular c-di-GMP inV. cholerae. We identified four c-di-GMP turnover enzymes that contribute to increased intracellular c-di-GMP in the presence of bile acids, and deletion of these enzymes eliminates the bile induction of c-di-GMP and biofilm formation. Furthermore, this bile-mediated increase in c-di-GMP is quenched by bicarbonate, the intestinal pH buffer secreted by intestinal epithelial cells. Our results lead us to propose thatV. choleraesenses distinct microenvironments within the small intestine using bile and bicarbonate as chemical cues and responds by modulating the intracellular concentration of c-di-GMP.

scholarly journals Growth faltering regardless of chronic diarrhea is associated with mucosal immune dysfunction and microbial dysbiosis in the gut lumen

2021 ◽  
Author(s):  
Nicholas S. Rhoades ◽  
Sara M. Hendrickson ◽  
Kamm Prongay ◽  
Andrew Haertel ◽  
Leanne Gill ◽  
...  
Keyword(s):  
Lamina Propria ◽  
Diarrheal Disease ◽  
Intestinal Inflammation ◽  
Rhesus Macaques ◽  
Valuable Insight ◽  
Microbial Dysbiosis ◽  
Growth Faltering ◽  
Healthy Infants ◽  
Inflammatory State ◽  
The Impact

AbstractDespite the impact of childhood diarrhea on morbidity and mortality, our understanding of its sequelae has been significantly hampered by the lack of studies that examine samples across the entire intestinal tract. Infant rhesus macaques are naturally susceptible to human enteric pathogens and recapitulate the hallmarks of diarrheal disease such as intestinal inflammation and growth faltering. Here, we examined intestinal biopsies, lamina propria leukocytes, luminal contents, and fecal samples from healthy infants and those experiencing growth faltering with distant acute or chronic active diarrhea. We show that growth faltering in the presence or absence of active diarrhea is associated with a heightened systemic and mucosal pro-inflammatory state centered in the colon. Moreover, polyclonal stimulation of colonic lamina propria leukocytes resulted in a dampened cytokine response, indicative of immune exhaustion. We also detected a functional and taxonomic shift in the luminal microbiome across multiple gut sites including the migration of Streptococcus and Prevotella species between the small and large intestine, suggesting a decompartmentalization of gut microbial communities. Our studies provide valuable insight into the outcomes of diarrheal diseases and growth faltering not attainable in humans and lays the groundwork to test interventions in a controlled and reproducible setting.

scholarly journals The effect of the stress hormone cortisol on the metatranscriptome of the oral microbiome

2018 ◽  
Author(s):  
Ana E. Duran-Pinedo ◽  
Jose Solbiati ◽  
Jorge Frias-Lopez
Keyword(s):  
Expression Profiles ◽  
Biological Effects ◽  
Human Microbiome ◽  
Gene Expression Profiles ◽  
Oral Microbiome ◽  
Stress Hormone ◽  
Commensal Microbiota ◽  
Microbial Dysbiosis ◽  
Psychological Stressors ◽  
The Impact

ABSTRACTImbalances of the microbiome also referred to as microbial dysbiosis, could lead to a series of different diseases. One factor that has been shown to lead to dysbiosis of the microbiome is exposure to psychological stressors. Throughout evolution microorganisms of the human microbiome have developed systems for sensing host-associated signals such as hormones associated with those stressors, enabling them to recognize essential changes in its environment thus changing its expression gene profile to fit the needs of the new environment. The most widely accepted theory explaining the ability of hormones to affect the outcome of an infection involves the suppression of the immune system. Commensal microbiota is involved in stressor-induced immunomodulation, but other biological effects are not yet known. Here we present the impact that cortisol had on the community-wide transcriptome of the oral community. We used a metatranscriptomic approach to obtain first insights into the metabolic changes induced by this stress hormone as well as which members of the oral microbiome respond to the presence of cortisol in the environment. Our findings show that the stress hormone cortisol directly induces shifts in the gene expression profiles of the oral microbiome that reproduce results found in the profiles of expression of periodontal disease and its progression.

scholarly journals Giardia Colonizes and Encysts in High-Density Foci in the Murine Small Intestine

mSphere ◽  
2017 ◽  
Vol 2 (3) ◽  
Author(s):  
N. R. Barash ◽  
C. Nosala ◽  
J. K. Pham ◽  
S. G. McInally ◽  
S. Gourguechon ◽  
...  
Keyword(s):  
Small Intestine ◽  
Gastrointestinal Tract ◽  
Animal Models ◽  
Diarrheal Disease ◽  
Laboratory Culture ◽  
High Density ◽  
Proximal Small Intestine ◽  
High Parasite Density ◽  
High Parasite

ABSTRACT Giardia is a single-celled parasite causing significant diarrheal disease in several hundred million people worldwide. Due to limited access to the site of infection in the gastrointestinal tract, our understanding of the dynamics of Giardia infections in the host has remained limited and largely inferred from laboratory culture. To better understand Giardia physiology and colonization in the host, we developed imaging methods to quantify Giardia expressing bioluminescent physiological reporters in two relevant animal models. We discovered that parasites primarily colonize and encyst in the proximal small intestine in discrete, high-density foci. We also show that high parasite density contributes to encystation initiation. Giardia lamblia is a highly prevalent yet understudied protistan parasite causing significant diarrheal disease worldwide. Hosts ingest Giardia cysts from contaminated sources. In the gastrointestinal tract, cysts excyst to become motile trophozoites, colonizing and attaching to the gut epithelium. Trophozoites later differentiate into infectious cysts that are excreted and contaminate the environment. Due to the limited accessibility of the gut, the temporospatial dynamics of giardiasis in the host are largely inferred from laboratory culture and thus may not mirror Giardia physiology in the host. Here, we have developed bioluminescent imaging (BLI) to directly interrogate and quantify the in vivo temporospatial dynamics of Giardia infection, thereby providing an improved murine model to evaluate anti-Giardia drugs. Using BLI, we determined that parasites primarily colonize the proximal small intestine nonuniformly in high-density foci. By imaging encystation-specific bioreporters, we show that encystation initiates shortly after inoculation and continues throughout the duration of infection. Encystation also initiates in high-density foci in the proximal small intestine, and high density contributes to the initiation of encystation in laboratory culture. We suggest that these high-density in vivo foci of colonizing and encysting Giardia likely result in localized disruption to the epithelium. This more accurate visualization of giardiasis redefines the dynamics of the in vivo Giardia life cycle, paving the way for future mechanistic studies of density-dependent parasitic processes in the host. IMPORTANCE Giardia is a single-celled parasite causing significant diarrheal disease in several hundred million people worldwide. Due to limited access to the site of infection in the gastrointestinal tract, our understanding of the dynamics of Giardia infections in the host has remained limited and largely inferred from laboratory culture. To better understand Giardia physiology and colonization in the host, we developed imaging methods to quantify Giardia expressing bioluminescent physiological reporters in two relevant animal models. We discovered that parasites primarily colonize and encyst in the proximal small intestine in discrete, high-density foci. We also show that high parasite density contributes to encystation initiation.

The Patterns of Simultaneous Intraluminal Pressure Changes in the Human Proximal Small Intestine

1964 ◽  
Vol 47 (3) ◽  
pp. 258-268 ◽  
Author(s):  
Gerald Friedman ◽  
Jerome D. Waye ◽  
Leonard A. Weingarten ◽  
Henry D. Janowitz
Keyword(s):  
Small Intestine ◽  
Intraluminal Pressure ◽  
Proximal Small Intestine ◽  
Pressure Changes

scholarly journals Impact of Community-Led Total Sanitation and Hygiene on Prevalence of Diarrheal Disease and Associated Factors among Under-Five Children: A Comparative Cross-Sectional Study in Selected Woredas of Gamo Gofa Zone, Southern Ethiopia

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Agune Ashole Alto ◽  
Wanzahun Godana ◽  
Genet Gedamu
Keyword(s):  
Drinking Water ◽  
Diarrheal Disease ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional ◽  
Under Five ◽  
Under Five Children ◽  
Sanitation And Hygiene ◽  
The Impact ◽  
Gamo Gofa

Background. Diarrheal diseases are still one of the major causes of morbidity in under-five children in sub-Saharan Africa. In Ethiopia, diarrhea is responsible for 9% of all deaths and is the major cause of under-five mortality. Objective. To assess the impact of community-led total sanitation and hygiene on the prevalence of diarrheal disease and factors associated among under-five children in Gamo Gofa Zone. Methods. Community-based comparative cross-sectional study design was used to compare the impact of community-led total sanitation and hygiene intervention on under-five diarrheal disease. Multistage sampling method was employed. The data were collected by using pretested structured questionnaires. Data quality was ensured by daily supervision completeness and consistency. The data were coded, entered, and cleaned by using Epi Info version 7 and were analyzed by using SPSS version 20. Bivariate and multivariable analyses were carried out by using binary logistic regression. Significance was declared by using p value of <0.05 and AOR with 95% confidence intervals. Results. The response rate of this study was 93.3%. The overall diarrhea prevalence was 27.5% (CI = (24.06, 30.97)) which was 18.9% (CI = (14.94, 23.2)) in implemented and 36.2%. (CI = (30.41, 41.59)) in nonimplemented woredas. Children whose age was between 12 and 23 months (AOR = 1.6) and greater than 24 months (AOR = 5), availability of handwashing facilities (AOR = 4), disposal of waste in open field (AOR = 9.7), unimproved source of drinking water (AOR = 6.5), using only water for handwashing (AOR = 6), children who started complementary feeding less than 6 months (AOR = 5.6) and greater than 6 months (AOR = 5.2), and utensils used to feed children such as bottle (AOR = 3.9) were the factors positively associated with diarrhea. Conclusion. The overall prevalence of under-five diarrhea was 27.5%. The prevalence was low in CLTSH woredas as compared with non-CLTSH woredas. The study showed that handwashing facility, using only water for handwashing, open refuse disposal, and unimproved source of drinking water among under-five had a statistically significant association with diarrhea occurrence in CLTSH nonimplemented areas. Integrated efforts are needed from the Ministry of Health together with the WASH Project in improving drinking water, handwashing facilities, and solid waste disposal practices.

scholarly journals Dopamine Transporter Genetic Reduction Induces Morpho-Functional Changes in the Enteric Nervous System

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 465
Author(s):  
Silvia Cerantola ◽  
Valentina Caputi ◽  
Gabriella Contarini ◽  
Maddalena Mereu ◽  
Antonella Bertazzo ◽  
...  
Keyword(s):  
Nervous System ◽  
Small Intestine ◽  
Enteric Nervous System ◽  
Dopamine Transporter ◽  
Myenteric Plexus ◽  
Receptor Activation ◽  
D1 Receptor ◽  
Functional Changes ◽  
Neurochemical Coding ◽  
The Impact

Antidopaminergic gastrointestinal prokinetics are indeed commonly used to treat gastrointestinal motility disorders, although the precise role of dopaminergic transmission in the gut is still unclear. Since dopamine transporter (DAT) is involved in several brain disorders by modulating extracellular dopamine in the central nervous system, this study evaluated the impact of DAT genetic reduction on the morpho-functional integrity of mouse small intestine enteric nervous system (ENS). In DAT heterozygous (DAT+/−) and wild-type (DAT+/+) mice (14 ± 2 weeks) alterations in small intestinal contractility were evaluated by isometrical assessment of neuromuscular responses to receptor and non-receptor-mediated stimuli. Changes in ENS integrity were studied by real-time PCR and confocal immunofluorescence microscopy in longitudinal muscle-myenteric plexus whole-mount preparations (). DAT genetic reduction resulted in a significant increase in dopamine-mediated effects, primarily via D1 receptor activation, as well as in reduced cholinergic response, sustained by tachykininergic and glutamatergic neurotransmission via NMDA receptors. These functional anomalies were associated to architectural changes in the neurochemical coding and S100β immunoreactivity in small intestine myenteric plexus. Our study provides evidence that genetic-driven DAT defective activity determines anomalies in ENS architecture and neurochemical coding together with ileal dysmotility, highlighting the involvement of dopaminergic system in gut disorders, often associated to neurological conditions.

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