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Nature Immunology Sep 2023Omnivorous animals, including mice and humans, tend to prefer energy-dense nutrients rich in fat over plant-based diets, especially for short periods of time, but the...
Omnivorous animals, including mice and humans, tend to prefer energy-dense nutrients rich in fat over plant-based diets, especially for short periods of time, but the health consequences of this short-term consumption of energy-dense nutrients are unclear. Here, we show that short-term reiterative switching to 'feast diets', mimicking our social eating behavior, breaches the potential buffering effect of the intestinal microbiota and reorganizes the immunological architecture of mucosa-associated lymphoid tissues. The first dietary switch was sufficient to induce transient mucosal immune depression and suppress systemic immunity, leading to higher susceptibility to Salmonella enterica serovar Typhimurium and Listeria monocytogenes infections. The ability to respond to antigenic challenges with a model antigen was also impaired. These observations could be explained by a reduction of CD4 T cell metabolic fitness and cytokine production due to impaired mTOR activity in response to reduced microbial provision of fiber metabolites. Reintroducing dietary fiber rewired T cell metabolism and restored mucosal and systemic CD4 T cell functions and immunity. Finally, dietary intervention with human volunteers confirmed the effect of short-term dietary switches on human CD4 T cell functionality. Therefore, short-term nutritional changes cause a transient depression of mucosal and systemic immunity, creating a window of opportunity for pathogenic infection.
Topics: Humans; Mice; Animals; Mucous Membrane; Salmonella typhimurium; T-Lymphocytes; Immunity, Mucosal
PubMed: 37580603
DOI: 10.1038/s41590-023-01587-x -
Nature Communications Oct 2023Invasive non-typhoidal Salmonella (iNTS) disease manifesting as bloodstream infection with high mortality is responsible for a huge public health burden in sub-Saharan... (Review)
Review
Invasive non-typhoidal Salmonella (iNTS) disease manifesting as bloodstream infection with high mortality is responsible for a huge public health burden in sub-Saharan Africa. Salmonella enterica serovar Typhimurium (S. Typhimurium) is the main cause of iNTS disease in Africa. By analysing whole genome sequence data from 1303 S. Typhimurium isolates originating from 19 African countries and isolated between 1979 and 2017, here we show a thorough scaled appraisal of the population structure of iNTS disease caused by S. Typhimurium across many of Africa's most impacted countries. At least six invasive S. Typhimurium clades have already emerged, with ST313 lineage 2 or ST313-L2 driving the current pandemic. ST313-L2 likely emerged in the Democratic Republic of Congo around 1980 and further spread in the mid 1990s. We observed plasmid-borne as well as chromosomally encoded fluoroquinolone resistance underlying emergences of extensive-drug and pan-drug resistance. Our work provides an overview of the evolution of invasive S. Typhimurium disease, and can be exploited to target control measures.
Topics: Humans; Africa South of the Sahara; Drug Resistance, Microbial; Genomics; Salmonella Infections; Salmonella typhimurium
PubMed: 37872141
DOI: 10.1038/s41467-023-41152-6 -
Journal of Advanced Research Oct 2023The gut microbiome is vital for providing resistance against colonized pathogenicbacteria. Recently, specific commensal species have become recognized as important...
INTRODUCTION
The gut microbiome is vital for providing resistance against colonized pathogenicbacteria. Recently, specific commensal species have become recognized as important mediators of host defense against microbial infection by a variety of mechanisms.
OBJECTIVES
To examine the contribution of live and pasteurized A. muciniphila to defend against the intestinal pathogen Salmonella Typhimurium in a streptomycin-treated mouse model of infection.
METHODS
C57B6J mice were pretreated with phosphate-buffered saline (PBS), live Akkermansia muciniphila (AKK), and pasteurized A. muciniphila (pAKK) for two weeks, then mice were infected by S. Typhimurium SL 1344. 16S rRNA-based gut microbiota analysis was performed before and after infection. Bacterial counts in feces and tissues, histopathological analysis, gut barrier-related gene expression, and antimicrobial peptides were examined. Co-housing was performed to examine the role of microbiota in the change of susceptibility of mice to infection.
RESULTS
AKK and pAKK markedly decreased Salmonella fecal and systemic burdens and reduced inflammation during infection. Notably, further characterization of AKK and pAKK protective mechanisms revealed different candidate protective pathways. AKK promoted gutbarrier gene expression and the secretion of antimicrobial peptides, and co-housing studies suggested that AKK-associated microbial community played a role in attenuating infection. Moreover, pAKK had a positive effect on NLRP3 in infected mice. We verified that pretreatment of pAKK could promote the expression of NLRP3, and enhance the antimicrobial activity of macrophage, likely through increasing the production of reactive oxygen (ROS), nitric oxide (NO), and inflammatory cytokines.
CONCLUSION
Our study demonstrates that live or pasteurized A. muciniphila can be effective preventive measures for alleviating S. Typhimurium-induced disease, highlighting the potential of developing Akkermansia-based probiotics or postbiotics for the prevention of Salmonellosis.
Topics: Mice; Animals; Salmonella typhimurium; RNA, Ribosomal, 16S; NLR Family, Pyrin Domain-Containing 3 Protein; Verrucomicrobia; Salmonella Infections; Antimicrobial Peptides
PubMed: 36996967
DOI: 10.1016/j.jare.2023.03.008 -
Veterinary Research Jul 2023Chicken infection with Salmonella Typhimurium is an important source of foodborne human diseases. Salmonella colonizes the avian intestinal tract and more particularly...
Chicken infection with Salmonella Typhimurium is an important source of foodborne human diseases. Salmonella colonizes the avian intestinal tract and more particularly the caecum, without causing symptoms. This thus poses a challenge for the prevention of foodborne transmission. Until now, studies on the interaction of Salmonella with the avian gut intestine have been limited by the absence of in vitro intestinal culture models. Here, we established intestinal crypt-derived chicken organoids to better decipher the impact of Salmonella intracellular replication on avian intestinal epithelium. Using a 3D organoid model, we observed a significantly higher replication rate of the intracellular bacteria in caecal organoids than in ileal organoids. Our model thus recreates intracellular environment, allowing Salmonella replication of avian epithelium according to the intestinal segment. Moreover, an inhibition of the cellular proliferation was observed in infected ileal and caecal organoids compared to uninfected organoids. This appears with a higher effect in ileal organoids, as well as a higher cytokine and signaling molecule response in infected ileal organoids at 3 h post-infection (hpi) than in caecal organoids that could explain the lower replication rate of Salmonella observed later at 24 hpi. To conclude, this study demonstrates that the 3D organoid is a model allowing to decipher the intracellular impact of Salmonella on the intestinal epithelium cell response and illustrates the importance of the gut segment used to purify stem cells and derive organoids to specifically study epithelial cell -Salmonella interaction.
Topics: Humans; Animals; Salmonella typhimurium; Chickens; Intestines; Intestinal Mucosa; Cecum; Organoids
PubMed: 37525204
DOI: 10.1186/s13567-023-01189-3 -
Regulatory Toxicology and Pharmacology... Aug 2023Consumer use of cannabidiol (CBD) for personal wellness purposes has garnered much public interest. However, safety-related data on CBD in the public domain are limited,...
Consumer use of cannabidiol (CBD) for personal wellness purposes has garnered much public interest. However, safety-related data on CBD in the public domain are limited, including a lack of quality studies evaluating its genotoxic potential. The quality of available studies is limited due to the test material used (e.g., low CBD purity) and/or study design, leading some global regulatory agencies to highlight genotoxicity as an important data gap for CBD. To address this gap, the genotoxic potential of a pure CBD isolate was investigated in a battery of three genotoxicity assays conducted according to OECD testing guidelines. In an in vitro microbial reverse mutation assay, CBD up to 5000 μg/plate was negative in Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537, and Escherichia coli strain WP2 uvrA, with and without metabolic activation. Testing in an in vitro micronucleus assay was negative in human TK6 cells up to 10-11 μg/mL, with and without metabolic activation. Finally, an in vivo micronucleus assay conducted in male and female rats was negative for genotoxicity up to 1000 mg/kg-bw/d. Bioanalysis of CBD and its primary metabolite, 7-carboxy CBD, confirmed a dose-related increase in plasma exposure. Together, these assays indicate that CBD is unlikely to pose a genotoxic hazard.
Topics: Rats; Male; Humans; Female; Animals; Mutagenicity Tests; Cannabidiol; Micronucleus Tests; Salmonella typhimurium; DNA Damage; Escherichia coli
PubMed: 37271419
DOI: 10.1016/j.yrtph.2023.105425 -
Microbial Biotechnology Jun 2024Some bacteria, such as Escherichia coli (E. coli) and Salmonella typhimurium (S. typhimurium), have an inherent ability to locate solid tumours, making them a versatile... (Review)
Review
Some bacteria, such as Escherichia coli (E. coli) and Salmonella typhimurium (S. typhimurium), have an inherent ability to locate solid tumours, making them a versatile platform that can be combined with other tools to improve the tumour diagnosis and treatment. In anti-cancer therapy, bacteria function by carrying drugs directly or expressing exogenous therapeutic genes. The application of bacterial imaging in tumour diagnosis, a novel and promising research area, can indeed provide dynamic and real-time monitoring in both pre-treatment assessment and post-treatment detection. Different imaging techniques, including optical technology, acoustic imaging, magnetic resonance imaging (MRI) and nuclear medicine imaging, allow us to observe and track tumour-associated bacteria. Optical imaging, including bioluminescence and fluorescence, provides high-sensitivity and high-resolution imaging. Acoustic imaging is a real-time and non-invasive imaging technique with good penetration depth and spatial resolution. MRI provides high spatial resolution and radiation-free imaging. Nuclear medicine imaging, including positron emission tomography (PET) and single photon emission computed tomography (SPECT) can provide information on the distribution and dynamics of bacterial population. Moreover, strategies of synthetic biology modification and nanomaterial engineering modification can improve the viability and localization ability of bacteria while maintaining their autonomy and vitality, thus aiding the visualization of gut bacteria. However, there are some challenges, such as the relatively low bacterial abundance and heterogeneously distribution within the tumour, the high dimensionality of spatial datasets and the limitations of imaging labeling tools. In summary, with the continuous development of imaging technology and nanotechnology, it is expected to further make in-depth study on tumour-associated bacteria and develop new bacterial imaging methods for tumour diagnosis.
Topics: Neoplasms; Humans; Escherichia coli; Bacteria; Salmonella typhimurium; Diagnostic Imaging; Animals; Optical Imaging
PubMed: 38808743
DOI: 10.1111/1751-7915.14474 -
Microbiological Research Oct 2023Inflammasome activation is a critical defense mechanism against bacterial infection. Previous studies suggest that inflammasome activation protects against Salmonella...
Inflammasome activation is a critical defense mechanism against bacterial infection. Previous studies suggest that inflammasome activation protects against Salmonella oral infection. Here we find inflammasome activation plays a critical role in the pathogenesis of Salmonella systemic infection. We show that in a systemic infection model by i.p. injection of Salmonella, deficiency of caspase-1 or gasdermin-D prolonged survival time, reduced plasma concentrations of the proinflammatory cytokines IL-1β, IL-6 and TNFα. These deficiencies also protected against coagulopathy during Salmonella infection as evidenced by diminished prolongation of prothrombin time and increase in plasma thrombin-antithrombin complex concentrations in the caspase-1 or gasdermin-D deficient mice. Activation of the NAIP/NLRC4 inflammasome by flagellin and/or the components of the SPI1 type 3 secretion system played a critical role in Salmonella-induced coagulopathy. In the absence of flagellin and SPI1, the Salmonella mutant strain still triggered coagulopathy through the caspase-11/NLRP3 pathway. Our results reveal a previously undisclosed role of the inflammasomes and pyroptosis in the pathogenesis of Salmonella systemic infection.
Topics: Mice; Animals; Inflammasomes; Pyroptosis; Flagellin; Calcium-Binding Proteins; Apoptosis Regulatory Proteins; Gasdermins; Caspases; Salmonella typhimurium; Caspase 1; Salmonella Infections; Inflammation
PubMed: 37467711
DOI: 10.1016/j.micres.2023.127460 -
Pathogens (Basel, Switzerland) Oct 2023is one of the most spread foodborne pathogens worldwide, and infections in humans still represent a global health burden. The main source of infections in humans is... (Review)
Review
is one of the most spread foodborne pathogens worldwide, and infections in humans still represent a global health burden. The main source of infections in humans is represented by contaminated animal-derived foodstuffs, with pork products being one of the most important players. infection in swine is critical not only because it is one of the main causes of economic losses in the pork industry, but also because pigs can be infected by several serovars, potentially contaminating the pig meat production chain and thus posing a significant threat to public health globally. As of now, in Europe and in the United States, swine-related serovars, e.g., Typhimurium and its monophasic variant subsp. 1,4,[5],12:i:-, are also frequently associated with human salmonellosis cases. Moreover, multiple outbreaks have been reported in the last few decades which were triggered by the consumption of -contaminated pig meat. Throughout the years, changes and evolution across the pork industry may have acted as triggers for new issues and obstacles hindering control along the food chain. Gathered evidence reinforces the importance of coordinating control measures and harmonizing monitoring programs for the efficient control of in swine. This is necessary in order to manage outbreaks of clinical disease in pigs and also to protect pork consumers by controlling subclinical carriage and shedding. This review provides an update on infection in pigs, with insights on ecology, focusing mainly on Choleraesuis, . Typhimurium, and . 1,4,[5],12:i:-, and their correlation to human salmonellosis cases. An update on surveillance methods for epidemiological purposes of infection in pigs and humans, in a "One Health" approach, will also be reported.
PubMed: 37887782
DOI: 10.3390/pathogens12101267 -
International Journal of Food Science 2023is a foodborne zoonotic pathogen causing diarrhoeal disease to humans after consuming contaminated water, animal, and plant products. The bacterium is the third leading... (Review)
Review
is a foodborne zoonotic pathogen causing diarrhoeal disease to humans after consuming contaminated water, animal, and plant products. The bacterium is the third leading cause of human death among diarrhoeal diseases worldwide. Therefore, human salmonellosis is of public health concern demanding integrated interventions against the causative agent, The prevention of salmonellosis in humans is intricate due to several factors, including an immune-stable individual infected with continuing to shed live bacteria without showing any clinical signs. Similarly, the asymptomatic animals are the source of salmonellosis in humans after consuming contaminated food products. Furthermore, the contaminated products of plant and animal origin are a menace in food industries due to biofilms, which enhance colonization, persistence, and survival of bacteria on equipment. The contaminated food products resulting from bacteria on equipment offset the economic competition of food industries and partner institutions in international business. The most worldwide prevalent broad-range serovars affecting humans are S Typhimurium and Enteritidis, and poultry products, among others, are the primary source of infection. The broader range of serovars creates concern over multiple strategies for preventing and controlling contamination in foods to enhance food safety for humans. Among the strategies for preventing and controlling spread in animal and plant products include biosecurity measures, isolation and quarantine, epidemiological surveillance, farming systems, herbs and spices, and vaccination. Other measures are the application of phages, probiotics, prebiotics, and nanoparticles reduced and capped with antimicrobial agents. Therefore, -free products, such as beef, pork, poultry meat, eggs, milk, and plant foods, such as vegetables and fruits, will prevent humans from infection. This review explains infection in humans caused by consuming contaminated foods and the interventions against contamination in foods to enhance food safety and quality for humans.
PubMed: 37727836
DOI: 10.1155/2023/8899596 -
Seminars in Immunology Nov 2023Besides its crucial function in nutrient absorbance and as barrier against the microbiota, the gut epithelium is essential for sensing pathogenic insults and mounting of... (Review)
Review
Besides its crucial function in nutrient absorbance and as barrier against the microbiota, the gut epithelium is essential for sensing pathogenic insults and mounting of an appropriate early immune response. In mice, the activation of the canonical NAIP/NLRC4 inflammasome is critical for the defense against enterobacterial infections. Activation of the NAIP/NLRC4 inflammasome triggers the extrusion of infected intestinal epithelial cells (IEC) into the gut lumen, concomitant with inflammasome-mediated lytic cell death. The membrane permeabilization, a hallmark of pyroptosis, is caused by the pore-forming proteins called gasdermins (GSDMs). Recent work has revealed that NAIP/NLRC4-dependent extrusion of infected IECs can, however, also be executed in the absence of GSDMD. In fact, several reports highlighted that various cell death pathways (e.g., pyroptosis or apoptosis) and unique mechanisms specific to particular infection models and stages of gut infection are in action during epithelial inflammasome defense against intestinal pathogens. Here, we summarize the current knowledge regarding the underlying mechanisms and speculate on the putative functions of the epithelial inflammasome activation and cell death, with a particular emphasis on mouse infection models for two prominent enterobacterial pathogens, Salmonella Typhimurium and Shigella flexneri.
Topics: Mice; Animals; Humans; Inflammasomes; Gasdermins; Salmonella typhimurium; Shigella; Inflammation
PubMed: 37562110
DOI: 10.1016/j.smim.2023.101812