Intestinal Bacterial Infections Research Articles

Oxidative stress in gut TH17 cells makes mice susceptible to bacterial infection.

A recent paper published in Cell Metabolism in August 2024 by Dirk Brenner's laboratory highlights the importance of effectively managing reactive oxygen species (ROS) in gut TH17 T cells for minimizing the damage caused by intestinal bacterial infection. This commentary will discuss the control of cellular ROS by glutathione and the emerging understanding that neutralizing ROS in immune cells is essential for the individualized functions of different immune subsets. In the case of this study, managing ROS within TH17 cells in the gut was shown to be essential to sustain the production of IL22 cytokine to maintain gut homeostasis in response to bacterial infection.

Lipopolysaccharide accelerates peristalsis by stimulating glucagon-like peptide-1 release from L cells in the rat proximal colon.

Upon epithelial barrier dysfunction, lipopolysaccharide (LPS) stimulates glucagon-like peptide-1 (GLP-1) secretion from enteroendocrine L cells by activating Toll-like receptor 4 (TLR4). Because GLP-1 accelerates peristalsis in the proximal colon, the present study aimed to explore whether LPS facilitates colonic peristalsis by stimulating L cell-derived GLP-1 release. In isolated segments of rat proximal colon that were serosally perfused with physiological salt solution and luminally perfused with 0.9% saline, peristaltic wall motion was video recorded and converted into spatio-temporal maps. Fluorescence immunohistochemistry was also carried out. Intraluminal administration of LPS (100 or 1µgmL-1 but not 100ngmL-1) increased the frequency of oro-aboral propagating peristaltic contractions. The LPS-induced acceleration of colonic peristalsis was blocked by TAK-242 (the TLR4 antagonist), exendin-3 (the GLP-1 receptor antagonist) or BIBN4096 (the calcitonin gene-related peptide receptor antagonist). GLP-1-positive epithelial cells co-expressed TLR4 immunoreactivity. In aspirin-pretreated preparations where epithelial barrier function had been impaired, a lower dose of LPS (100ngmL-1) became capable of accelerating peristalsis. By contrast, luminally applied dimethyl sulphoxide, a reactive oxygen species scavenger that protects epithelial integrity, attenuated the prokinetic effects of a higher dose of LPS (100µgmL-1). In colonic segments of a stress rat model leading to a leaky gut, LPS induced more pronounced prokinetic effects. Colonic L cells may well sense luminal LPS via TLR4 triggering the release of GLP-1 that stimulates calcitonin gene-related peptide-containing neurons. The resultant acceleration of peristalsis would facilitate excretion of Gram-negative bacteria from the intestine, and thus L cells may have a protective role against intestinal bacterial infections. KEY POINTS: Colonic epithelial cells form a barrier against bacterial invasion but also may contribute more actively to the exclusion of luminal pathogen by stimulating colonic motility. Luminal lipopolysaccharide (LPS) accelerated colonic peristalsis by stimulating calcitonin gene-related peptide-containing neurons. The prokinetic effect of LPS was mediated by the secretion of glucagon-like peptide-1 from enteroendocrine L cells in which Toll-like receptor 4 was expressed. The LPS-mediated acceleration of peristalsis depended on epithelial barrier integrity. L cells have a defensive role against Gram-negative bacterial infections by facilitating faecal excretion, and could be a potential therapeutic target for gastrointestinal infections.

Gut-Brain Nexus: Mapping Multi-Modal Links to Neurodegeneration at Biobank Scale.

Alzheimer's disease (AD) and Parkinson's disease (PD) are influenced by genetic and environmental factors. Using data from UK Biobank, SAIL Biobank, and FinnGen, we conducted an unbiased, population-scale study to: 1) Investigate how 155 endocrine, nutritional, metabolic, and digestive system disorders are associated with AD and PD risk prior to their diagnosis, considering known genetic influences; 2) Assess plasma biomarkers' specificity for AD or PD in individuals with these conditions; 3) Develop a multi-modal classification model integrating genetics, proteomics, and clinical data relevant to conditions affecting the gut-brain axis. Our findings show that certain disorders elevate AD and PD risk before AD and PD diagnosis including: insulin and non-insulin dependent diabetes mellitus, noninfective gastro-enteritis and colitis, functional intestinal disorders, and bacterial intestinal infections, among others. Polygenic risk scores revealed lower genetic predisposition to AD and PD in individuals with co-occurring disorders in the study categories, underscoring the importance of regulating the gut-brain axis to potentially prevent or delay the onset of neurodegenerative diseases. The proteomic profile of AD/PD cases was influenced by comorbid endocrine, nutritional, metabolic, and digestive systems conditions. Importantly, we developed multi-modal prediction models integrating clinical, genetic, proteomic and demographic data, the combination of which performs better than any single paradigm approach in disease classification. This work aims to illuminate the intricate interplay between various physiological factors involved in the gut-brain axis and the development of AD and PD, providing a multifactorial systemic understanding that goes beyond traditional approaches.

Dietary supplementation with a novel acidifier sodium diformate improves growth performance by increasing growth-related hormones levels and prevents Salmonella enterica serovar Pullorum infection in chickens.

Since the use of antibiotics as growth promoters in animal feed has been restricted or banned in several countries, finding suitable alternatives is crucial for maintaining animal health. In this study, a novel formate acidifier named sodium diformate (NaDF) was synthesized, and the effects on growth performance and the prevention effects against Salmonella enterica serovar Pullorum infections in chickens were assessed. In broilers, NaDF supplementation improved growth performance, as evidenced by increased body weights and reduced feed conversion ratios. At 38 days of age, NaDF supplementation increased the levels of growth-hormone and ghrelin in the serum, lowered pH values in the gut, improved duodenal morphology, as shown by increased villus length/crypt depth ratios. NaDF also modulated the abundance of beneficial and harmful bacteria without changing the general microbiota diversity and short-chain fatty acids levels, which would be beneficial for maintaining gut homeostasis during its use. NaDF exhibited a broad spectrum of antibacterial activity in vitro. Supplementation with NaDF effectively decreased S. Pullorum colonization in the cecum, liver and spleen in chickens, and mitigated pathological changes in the tissues. Therefore, as a novel acidifier, NaDF can improve chicken growth performance by increasing growth-related hormones levels while maintaining the diversity of gut microbiota, and also resist intestinal bacterial infection. These results provided evidences for the application of NaDF as an effective and safe animal feed in poultry farming.

Choice of treatment tactics in patients with acute bacterial intestinal infections who have a high risk of developing irritable bowel syndrome

Choice of treatment tactics in patients with acute bacterial intestinal infections who have a high risk of developing irritable bowel syndrome

GSDMD protects intestinal epithelial cells against bacterial infections through its N-terminal activity impacting intestinal immune homeostasis.

The intestinal mucosal barrier serves as a vital guardian for gut health, maintaining a delicate equilibrium between gut microbiota and host immune homeostasis. Recent studies have found the intricate roles of Gasdermin D (GSDMD), a key executioner of pyroptosis downstream of the inflammasome, within the intestine, including controlling colitis in intestinal macrophage and the regulatory function in goblet cell mucus secretion. Thus, the exact role and nature of GSDMD's regulatory function in maintaining intestinal immune homeostasis and defending against pathogens remain elucidation. Here, we uncover that GSDMD plays a key role in defending against intestinal Citrobacter rodentium infection, with high expression in intestinal epithelial and lamina propria myeloid cells. Our results show that GSDMD specifically acts in intestinal epithelial cells to fight the infection, independently of its effects on antimicrobial peptides or mucin secretion. Instead, the resistance is mediated through GSDMD's N-terminal fragments, highlighting its importance in intestinal immunity. However, the specific underlying mechanism of GSDMD N-terminal activity in protection against intestinal bacterial infections still needs further study to clarify in the future.

PREVENTION OF INTESTINAL INFECTIONS OF BACTERIAL ETIOLOGY IN PIGS

Intestinal infections of bacterial etiology are among the most common diseases in pigs of different age groups. Healthy gastrointestinal tract is the basis for successful pig farming. Therefore, the prevention and control of major gastrointestinal infections is a key to farm profitability. Intestinal infections are caused by both pathogenic and opportunistic pathogenic bacteria. The most common diseases caused by pathogenic microorganisms include dysentery, ileitis and salmonellosis. Their causative agents are the bacteria Brachyspira spp., Lawsonia spp. and Salmonella spp. respectively. The most common opportunistic pathogenic bacteria are: Escherichia coli, Clostridium spp. and Proteus spp. Bacterial intestinal infections are diverse and widespread, and therefore cause significant economic losses for livestock farms. They suffer significant losses due to animal mortality, reduced productivity and, as a result, increased treatment costs. Therefore, the efforts of scientists should be aimed at creating innovative approaches and effective therapeutic agents that would not only treat but also prevent bacterial intestinal infections. The article presents data on traditional and innovative approaches to the prevention of bacterial intestinal infections in pigs. The advantages of using feed additives for the prevention and treatment of bacterial intestinal infections in pigs are described.

Metagenomic investigation of intestinal bacterial and parasitic infections in urban canines in Seoul, Korea

Metagenomic investigation of intestinal bacterial and parasitic infections in urban canines in Seoul, Korea

Systemic Effects of a Phage Cocktail on Healthy Weaned Piglets.

Numerous studies have demonstrated that bacteriophages (phages) can effectively treat intestinal bacterial infections. However, research on the impact of phages on overall body health once they enter the intestine is limited. This study utilized weaned piglets as subjects to evaluate the systemic effects of an orally administered phage cocktail on their health. Twelve 21-day-old weaned piglets were divided into control (CON) and phage gavage (Phages) groups. The phage cocktail consisted of five lytic phages, targeting Salmonella enterica serovar Choleraesuis (S. choleraesuis), Enteropathogenic Escherichia coli (EPEC), and Shiga tox-in-producing Escherichia coli (STEC). The phages group received 10 mL of phage cocktail orally for 20 consecutive days. The results show that the phage gavage did not affect the piglets' growth performance, serum biochemical indices, or most organ indices, except for the pancreas. However, the impact on the intestine was complex. Firstly, although the pancreatic index decreased, it did not affect the secretion of digestive enzymes in the intestine. Secondly, phages increased the pH of jejunum chyme and relative weight of the ileum, and enhanced intestinal barrier function without affecting the morphology of the intestine. Thirdly, phages did not proliferate in the intestine, but altered the intestinal microbiota structure and increased concentrations of microbial metabolites isobutyric acid and isovaleric acid in the colonic chyme. In addition, phages impacted the immune status, significantly increasing serum IgA, IgG, and IgM, as well as serum and intestinal mucosal IFN-γ, IL-1β, IL-17, and TGF-β, and decreasing IL-4 and IL-10. They also activated toll-like receptors TLR-4 and TLR-9. Apart from an increase in basophil numbers, the counts of other immune cells in the blood did not change. This study indicates that the impact of phages on body health is complex, especially regarding immune status, warranting further attention. Short-term phage gavage did not have significant negative effects on health but could enhance intestinal barrier function.

Infection and antibiotic-associated changes in the fecal microbiota of C. rodentium ϕstx2dact-infected C57BL/6 mice.

Enterohemorrhagic Escherichia coli causes watery to bloody diarrhea, which may progress to hemorrhagic colitis and hemolytic-uremic syndrome. While early studies suggested that antibiotic treatment may worsen the pathology of an enterohemorrhagic Escherichia coli (EHEC) infection, recent work has shown that certain non-Shiga toxin-inducing antibiotics avert disease progression. Unfortunately, both intestinal bacterial infections and antibiotic treatment are associated with dysbiosis. This can alleviate colonization resistance, facilitate secondary infections, and potentially lead to more severe illness. To address the consequences in the context of an EHEC infection, we used the established mouse infection model organism Citrobacter rodentium ϕstx2dact and monitored changes in fecal microbiota composition during infection and antibiotic treatment. C. rodentium ϕstx2dact infection resulted in minor changes compared to antibiotic treatment. The infection caused clear alterations in the microbial community, leading mainly to a reduction of Muribaculaceae and a transient increase in Enterobacteriaceae distinct from Citrobacter. Antibiotic treatments of the infection resulted in marked and distinct variations in microbiota composition, diversity, and dispersion. Enrofloxacin and trimethoprim/sulfamethoxazole, which did not prevent Shiga toxin-mediated organ damage, had the least disruptive effects on the intestinal microbiota, while kanamycin and tetracycline, which rapidly cleared the infection without causing organ damage, caused a severe reduction in diversity. Kanamycin treatment resulted in the depletion of all but Bacteroidetes genera, whereas tetracycline effects on Clostridia were less severe. Together, these data highlight the need to address the impact of individual antibiotics in the clinical care of life-threatening infections and consider microbiota-regenerating therapies.IMPORTANCEUnderstanding the impact of antibiotic treatment on EHEC infections is crucial for appropriate clinical care. While discouraged by early studies, recent findings suggest certain antibiotics can impede disease progression. Here, we investigated the impact of individual antibiotics on the fecal microbiota in the context of an established EHEC mouse model using C. rodentium ϕstx2dact. The infection caused significant variations in the microbiota, leading to a transient increase in Enterobacteriaceae distinct from Citrobacter. However, these effects were minor compared to those observed for antibiotic treatments. Indeed, antibiotics that most efficiently cleared the infection also had the most detrimental effect on the fecal microbiota, causing a substantial reduction in microbial diversity. Conversely, antibiotics showing adverse effects or incomplete bacterial clearance had a reduced impact on microbiota composition and diversity. Taken together, our findings emphasize the delicate balance required to weigh the harmful effects of infection and antibiosis in treatment.

Main Manifestations of the Epidemic Process of Acute Intestinal Infections in the Far Eastern Federal District in 2022

Background: Diarrheal diseases consistently occupy one of the leading positions in the structure of infections, especially in children under the age of 5 years. A decrease in the incidence of bacterial intestinal infections and an increase in viral ones have been observed recently with an uneven territorial distribution of registered cases. Objective: To characterize the main manifestations of the epidemic process of acute intestinal infections in the Far Eastern Federal District of the Russian Federation in 2022. Materials and methods: Based on official statistics, we analyzed the incidence of acute intestinal infections by age groups, types, and administrative territories of the federal district; we also examined the outbreaks of these infections registered in 2022. Results: We established that the incidence rates of almost all leading acute intestinal infections (except for shigellosis) in the Far Eastern Federal District were higher than the Russian averages. Viral infections prevailed in the diarrhea cases with identified pathogens. Children under 6 years of age were found to be the most affected population while the highest incidence was observed in the age group of 1–2 years. We noted differences between the areas of the District and established higher disease rates in 4 of its 11 regions. Oral and direct contact routes of transmission generally prevailed, especially in collectives, leading to outbreaks. Conclusion: In general, the manifestations of the epidemic process of acute intestinal infections noted in 2022 indicate the persistence of potential epidemiologic risks of both sporadic cases and outbreaks on the territories of the Far East.

A33 EOSINOPHILS PROMOTE SALMONELLA TYPHIMURIUM COLONIZATION IN THE MURINE SMALL INTESTINE

Abstract Background During inflammatory bowel disease (IBD) both the number of intestinal eosinophils and susceptibility to enteric bacterial infections can drastically increase. It is unknown, however, whether eosinophils recruited to the tissues lining the gastrointestinal (GI) tract during severe disease help to control pathogenic bacterial colonization or whether their presence promotes bacterial infection. No studies to date have examined the role of eosinophils during an acute bacterial infection in the small intestine. Aims Our research aims to uncover the role of eosinophils during an enteric Salmonella infection in mice and we hypothesize that eosinophils undergo phenotypic changes in the presence of Salmonella and aid in the clearance of this enteric bacterial pathogen. Methods To assess how the presence of Salmonella impacts the frequency and phenotype of eosinophils we performed flow cytometry on eosinophils isolated from mice 3-days post-oral infection with Salmonella enterica serovar Typhimurium and compared these findings to naïve BALB/c controls. To determine if eosinophils are essential for controlling Salmonella infection we quantified levels of Salmonella colonization along the GI tract, liver and spleen of wild-type and eosinophil-deficient (ΔdblGATA) littermate mice by plating homogenized tissues on LB agar. Results Following an oral Salmonella infection we found higher frequencies of eosinophils in the gut-draining mesenteric lymph nodes compared to uninfected mice. Intestinal lamina propria-resident eosinophils in the small intestine and colon displayed altered phenotypes following infection in an intestinal-region specific manner: during infection, in the small intestine eosinophils increased their expression of MHCII, and in the colon eosinophils displayed elevated granularity. When wild-type and ΔdblGATA mice were pre-treated with the antibiotic streptomycin 1-day prior to infection to confer robust Salmonella burdens in the small intestine we found a significant reduction in Salmonella colonization in the ileum of the small intestine in ΔdblGATA mice compared to their wild-type littermates. These data suggest eosinophils have a role in promoting colonization by this enteric bacterial pathogen. Conclusions Our data contribute to the growing evidence that microbes can influence the phenotype of intestinal eosinophils and demonstrate that the influence of and requirements for eosinophils during bacterial infection is highly context-dependent. We found that eosinophils are not essential for controlling an acute enteric Salmonella infection and instead they promote Salmonella colonization in the small intestine. Funding Agencies CIHRTRIANGLE

Epidemiological characteristics of mortality from infectious intestinal diseases (diarrhea) Paraguay (2015-2019)

Introduction: Infectious intestinal diseases (diarrhea) are a major cause of morbidity and mortality worldwide. In 2015, it constituted the ninth leading cause of death for all ages. Objective: To describe the epidemiological characteristics of mortality due to infectious intestinal diseases (diarrhea) in Paraguay from 2015 to 2019. Methods: Descriptive, ecological, cross-sectional, retrospective, and non-probabilistic sampling of consecutive cases was performed. ICD-10 deaths included cholera (A01), typhoid and paratyphoid fever (A01), shigellosis (A03), other bacterial intestinal infections (A04), other bacterial food poisoning (A05), amebiasis (A06), other intestinal diseases due to protozoa (A07), intestinal infections due to viruses (A08), and diarrhea and gastroenteritis of presumed infectious origin (A09). Open access data were obtained from the WEB page of the General Directorate of Strategic Information in Health of the MSP and BS of all the Departments of the country. Crude and adjusted rates (per 100,000 inhabitants) were calculated. Excel and EPI INFO 7.0 were used. Results: 495 deaths were registered; the highest prevalence was in 2019 (adjusted rate of 1.83) and the lowest in 2017 (1.36). The months with the highest mortality rates were January and July (9.9%). 51.72% were women (256), 30.91% were over 80 years old and 28.28% (140) were under 5 years old, average age 50.8, single 56.77% (281) and without any type of education 41.82% (207). A total of 80.61% (399) of the respondents resided in urban areas. The highest rates were registered in Boquerón (33.3) and Amambay (15.2). Diarrhea and gastroenteritis of infectious origin accounted for 95.56% of the cases (473). Discussion: There was a high percentage of mortality from infectious diarrhea. Extremes of life were the most vulnerable populations.

Evaluation of Natural Antimicrobial Substances Blend as a Replacement for Antibiotic Growth Promoters in Broiler Chickens: Enhancing Growth and Managing Intestinal Bacterial Diseases.

In recent years, commercial use of antibiotic growth promoter (AGP) has restrictions due to drug resistance against intestinal pathogenic bacteria: Escherichia coli, Salmonella, and Clostridium perfringens. Currently there is no single non-antibiotic treatment approach that is effective against intestinal illnesses in broiler chicken. Hence, present study aimed to analyze efficacy of blend of natural antimicrobial substances (probiotics, prebiotics, organic acids, and essential oils blend named as AGPR) as replacers of AGPs (BMD and CTC) for promoting growth and controlling bacterial diseases in aforementioned three microbes challenged broiler chickens. Effects of treatments (5) and microbes (3) on growth and health performances in experimental birds were analyzed using two factorial ANOVA. Health performance like pathogen loads, morbidity and mortality was considerably reduced by AGPR. Similarly small intestine villi morphometry, nutrition utilization, serum immune response, and carcass yield, was improved significantly by AGPR equivalent to AGPs. Further, growth performance like body weight gain, feed efficiency was also improved by AGPR compared to control but, non-significantly. Among three microbes, E. coli infections had higher morbidity and mortality rates. It was concluded that AGPR blend could be used to improve growth and control the intestinal bacterial infections in broiler chickens as an alternative for AGPs.

The impact of management on the fecal microbiome of endangered greater sage-grouse (Centrocercus urophasianus) in a zoo-based conservation program.

Greater sage-grouse (Centrocercus urophasianus) are a critically endangered species in Canada with fewer than 140 individuals remaining on native habitats in southern Alberta and Saskatchewan. In 2014, the Wilder Institute/Calgary Zoo initiated North America's only zoo-based conservation breeding program for this species to bolster declining wild populations through conservation reintroductions. Within the managed population of sage-grouse, morbidity and mortality have primarily been associated with intestinal bacterial infections. As a preliminary study to assess the gastrointestinal health of this species in managed care, the fecal bacterial microbiome of adult and juvenile captive sage-grouse was characterized with 16S rRNA sequencing. The composition of the microbiome at the phylum level in greater sage-grouse is consistent with previous studies of the avian microbiome, with Bacillota as the most abundant phyla, and Actinomycetota, Bacteroidota and Pseudomonadota also being highly abundant. Antibiotic use and sex did not have a significant impact on the diversity or composition of the microbiome, but the management of juvenile sage-grouse did influence the development of the microbiome. Juveniles that were raised outdoors under maternal care developed a microbiome much more similar to adults when compared to chicks that were incubated and hand-raised. The local environment and parental care appear to be important factors influencing the diversity and composition of the gastrointestinal microbiome in this species.

Review on probiotics and prebiotics' in healthcare poultry's prevention of intestinal bacterial infection

Review on probiotics and prebiotics' in healthcare poultry's prevention of intestinal bacterial infection

Results of the archaeoparasitological analysis of soil samples from the necropolis of the 2nd c. AD settlement of Pantikapaion

In the paper, the results of an archaeoparasitological analysis of a population group from the ancient Greek city of Panti-kapaion, located in the historical centre of the modern city of Kerch (Republic of Crimea), are presented. The aim of the study is to obtain information about the parasitic diseases, state of health, nutrition, and hygiene in a part of the population of the city. The materials for the study were soil samples obtained during the treatment of the human sacra from 31 burials of the necropo-lis, dated to the 2nd century AD. In the result of the conducted investigation, the parasitic spectrum of the studied population group was determined. Eggs of three species of helminths were found. The discovery of eggs of broad tapeworm (Dibothrio-cephalus latum) in the soil samples indicates the presence in the diet of the studied population group freshwater fish that were not sufficiently thermally treated. The archaeoparasitological data from archaeological sites of a chronologically close period in the territory of the Northern Black Sea region suggests that diphyllobothriasis was a decease far from being rare in this area. The presence of eggs of human roundworm (Ascaris lumbricoides) and whipworm (Trichuris trichiura) in the samples likely indicates the challenging sanitary-hygienic environment in the city and insufficient hygienic skills in the studied group. The analysis of the archaeoparasitological data within the historical context and utilisation of the archaeopathological material from the archaeological sites in the Northern Black Sea region permitted to identify the factors that had an influence on the wide spread of geohelminths. The humid and warm climate facilitated maturation of geohelminth eggs in the soil, while the human activities concerned with the irrigation of the territory, building public water collection points, and waste buildup in the streets, in combination with the high population density, were causing the rise of the infectious hazard. The relatively high incidence rates of Trichuris trichiura and Ascaris lumbricoides may indicate a high prevalence of certain bacterial intestinal infections transmitted by the identical route. The occurrence of geohelminths, alongside the archaeological data, can indicate a low social status of the studied population group.

Evaluation of the dietary L-valine on fish growth and intestinal health after infection with Aeromonas veronii

Endoplasmic reticulum stress and subsequent apoptosis play a pivotal role in bacterial infection in intestine. The objective of this study was to assess the influence of dietary L-valine (Val) on growth, antioxidant capacity, and endoplasmic reticulum stress-mediated apoptosis in the intestine of juvenile largemouth bass Micropterus punctulatus following an Aeromonas veronii infection. A total of 720 fish were randomly assigned to six groups and provided with varying levels of Val for 77 days. Subsequently, they were challenged with A. veronii. Our results revealed that dietary Val: (1) increased percent weight gain (PWG), specific growth rate (SGR), feed intake (FI), feed efficiency (FE), protein efficiency ratio (PER), protein production value (PPV), lipid production value (LPV), ash production value (APV) and survival rate (SR). Additionally, it alleviated A. veronii-induced intestinal injury; (2) improved intestinal antioxidant capacity by enhancing the mRNA levels of superoxide dismutase 1 (SOD1), catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), and glutamate-cysteine ligase catalytic subunit (GCLC) via the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway; (3) reduced intestinal DNA fragments and down-regulated glucose-regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), inositol-requiring enzyme 1 (IRE1), protein kinase-like ER kinase (PERK), eukaryotic Initiation Factor 2 (eIF2α), activating transcription factor 4 (ATF4), C/EBP homologous protein (CHOP), caspase 9, and caspase 3 mRNA levels through modulating the PERK/eIF2α signaling pathway. These findings suggest that optimal dietary Val enhances the growth performance, antioxidant capacity, and mitigates A. veronii-induced intestinal injury. Finally, the mitigates optimal Val requirement of largemouth bass (37.99–162.92 g) is 21.50 g/kg diet, corresponding to 46.64 g/kg protein.

The epidemiological characteristics and infection risk factors for extrapulmonary tuberculosis in patients hospitalized with pulmonary tuberculosis infection in China from 2017 to 2021

BackgroundPulmonary tuberculosis (PTB) complicated with extrapulmonary tuberculosis (EPTB) infection can aggravate the disease, but there have been few reports.MethodsRetrospective analysis was used to collect the clinical data of PTB patients with pathogen positive in a teaching hospital from 2017 to 2021. We describe the incidence, the invasive site of EPTB patients, and analyze the infection risk factors for PTB with EPTB by univariate and multivariate logistic regression models. We also compared the complications, disease burden with chi-square test and rank-sum test.ResultsA total of 1806 PTB were included, of which 263 (14.6%) were complicated with EPTB. The common invasive sites for EPTB were neck lymph nodes (16.49%), intestines (16.13%), and meninges (10.75%). Age ≤ 40 (OR = 1.735; 95%CI [1.267–2.376]; P = 0.001), malnutrition (OR = 2.029; 95%CI [1.097–3.753]; P = 0.022), anemia (OR = 1.739; 95%CI[1.127–2.683]; P = 0.012), and osteoporosis (OR = 4.147; 95%CI [1.577–10.905]; P = 0.004) were all independent risk factors for PTB infection with EPTB. The incidence of extrathoracic hydrothorax, intestinal bacterial infection, urinary tract bacterial infection, and abdominal bacterial infection were higher in patients with PTB with EPTB. PTB with EPTB patients also had longer median hospitalization durations (19 vs. 14 days), during which time they incurred higher total costs, laboratory test costs, imaging examination costs, and drug use costs.ConclusionThis study found important risk factors for PTB complicated with EPTB, such as age ≤ 40, malnutrition, anemia, and osteoporosis. PTB with EPTB patients have more extrapulmonary complications and higher hospitalization disease burden.

Liposomes Co-Delivering Curcumin and Colistin to Overcome Colistin Resistance in Bacterial Infections.

Antibiotic colistin is the last line of defense against multidrug-resistant (MDR) Gram-negative bacterial infections. Emergence of colistin resistance in microbes is a critical challenge. Herein, curcumin is discovered, for the first time, to reverse the resistance phenotype of colistin-resistant bacteria via a checkerboard assay. For the co-delivery of curcumin and colistin, negatively charged poly(ethylene glycol)-functionalized liposomes encapsulating both drugs (Lipo-cc) are prepared. Killing kinetics and live/dead assays confirm the antibacterial activity of Lipo-cc against colistin-resistant bacteria, which is more potent than that of the free curcumin and colistin combination. Mechanistical studies reveal that Lipo-cc restores the affinity of colistin for the bacterial membrane and improves the uptake of curcumin, which leads to reduced efflux pump activity, achieving a synergistic effect of colistin and curcumin. At the effective antibacterial dose, Lipo-cc does not exhibit any toxicity. The therapeutic efficacy of Lipo-cc is further demonstrated in an intestinal bacterial infection model induced with colistin-resistant Escherichia coli. Lipo-cc reduces the bacterial burden with over 6-log reduction and alleviated inflammation caused by infection. Importantly, unlike colistin, Lipo-cc does not affect the homeostasis of the intestinal flora. Taken together, Lipo-cc successfully overcame colistin resistance, indicating its potential for the treatment of colistin-resistant bacterial infections.