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American Journal of Veterinary Research Jul 2024Assess markers for pancreatic function and gastrointestinal malabsorption in African painted dogs (Lycaon pictus), including canine trypsin-like immunoreactivity (cTLI),...
Evaluation of trypsin-like immunoreactivity, pancreatic lipase immunoreactivity, cobalamin, and folate in zoo-housed African painted dogs (Lycaon pictus) at a North American zoological facility.
OBJECTIVE
Assess markers for pancreatic function and gastrointestinal malabsorption in African painted dogs (Lycaon pictus), including canine trypsin-like immunoreactivity (cTLI), canine pancreatic lipase immunoreactivity (cPLI), cobalamin, and folate at one North American facility.
ANIMALS
15 healthy African painted dogs held at one institution were sampled during routine health examinations.
METHODS
Blood was collected at routine health examinations, and serum was separated and stored until testing. Serum was analyzed for cTLI, cPLI, cobalamin, and folate. The results were evaluated for correlation to sex, age, and storage time of samples.
RESULTS
All individuals had cTLI and folate levels below normal reference ranges for domestic dogs (< 5.0 µg/L and < 7.7 µg/L, respectively). Cobalamin values were within or above reported domestic dog ranges, and cPLI values were within range as well. No analytes were significantly influenced by sex or time in storage, while cTLI was positively correlated with age.
CLINICAL RELEVANCE
cTLI and folate did not fall within normal domestic canid reference ranges in this population of healthy African painted dogs. Clinical interpretation of these values based on domestic canid recommendations would indicate clinical disease, which was not apparent in this population. Analytes for pancreatic function and malabsorption or gastrointestinal indicators, including cTLI, cPLI, and folate, in African painted dogs should be interpreted with caution when using domestic dog references ranges.
Topics: Animals; Male; Lipase; Female; Vitamin B 12; Animals, Zoo; Folic Acid; Canidae; Reference Values; Trypsin; Pancreas
PubMed: 38729202
DOI: 10.2460/ajvr.24.02.0043 -
MBio Jun 2024Bile acids play a critical role in the emulsification of dietary lipids, a critical step in the primary function of the small intestine, which is the digestion and...
UNLABELLED
Bile acids play a critical role in the emulsification of dietary lipids, a critical step in the primary function of the small intestine, which is the digestion and absorption of food. Primary bile acids delivered into the small intestine are conjugated to enhance functionality, in part, by increasing aqueous solubility and preventing passive diffusion of bile acids out of the gut lumen. Bile acid function can be disrupted by the gut microbiota via the deconjugation of primary bile acids by bile salt hydrolases (BSHs), leading to their conversion into secondary bile acids through the expression of bacterial bile acid-inducible genes, a process often observed in malabsorption due to small intestinal bacterial overgrowth. By modeling the small intestinal microbiota using human small intestinal ileostomy effluent as the inocula, we show here that the infusion of physiologically relevant levels of oxygen, normally found in the proximal small intestine, reduced deconjugation of primary bile acids, in part, through the expansion of bacterial taxa known to have a low abundance of BSHs. Further recapitulating the small intestinal bile acid composition of the small intestine, limited conversion of primary into secondary bile acids was observed. Remarkably, these effects were preserved among four separate communities, each inoculated with a different small intestinal microbiota, despite a high degree of taxonomic variability under both anoxic and aerobic conditions. In total, these results provide evidence for a previously unrecognized role that the oxygenated environment of the small intestine plays in the maintenance of normal digestive physiology.
IMPORTANCE
Conjugated primary bile acids are produced by the liver and exist at high concentrations in the proximal small intestine, where they are critical for proper digestion. Deconjugation of these bile acids with subsequent transformation via dehydroxylation into secondary bile acids is regulated by the colonic gut microbiota and reduces their digestive function. Using an platform modeling the small intestinal microbiota, we analyzed the ability of this community to transform primary bile acids and studied the effect of physiological levels of oxygen normally found in the proximal small intestine (5%) on this metabolic process. We found that oxygenation of the small intestinal microbiota inhibited the deconjugation of primary bile acids . These findings suggest that luminal oxygen levels normally found in the small intestine may maintain the optimal role of bile acids in the digestive process by regulating bile acid conversion by the gut microbiota.
Topics: Bile Acids and Salts; Humans; Intestine, Small; Gastrointestinal Microbiome; Oxygen; Bacteria; Amidohydrolases
PubMed: 38727244
DOI: 10.1128/mbio.00943-24 -
Life Science Alliance Jul 2024Celiac disease (CD) is an autoimmune enteropathy resulting from an interaction between diet, genome, and immunity. Although many patients respond to a gluten-free diet,...
Celiac disease (CD) is an autoimmune enteropathy resulting from an interaction between diet, genome, and immunity. Although many patients respond to a gluten-free diet, in a substantive number of individuals, the intestinal injury persists. Thus, other factors might amplify the ongoing inflammation. is a commensal fungus that is well adapted to the intestinal life. However, specific conditions increase pathogenicity. The hypothesis that may be a trigger in CD has been proposed after the observation of similarity between a fungal wall component and two CD-related gliadin T-cell epitopes. However, despite being implicated in intestinal disorders, may also protect against immune pathologies highlighting a more intriguing role in the gut. Herein, we postulated that a state of chronic inflammation associated with microbial dysbiosis and leaky gut are favorable conditions that promote pathogenicity eventually contributing to CD pathology via a mast cells (MC)-IL-9 axis. However, the restoration of immune and microbial homeostasis promotes a beneficial -MC cross-talk favoring the attenuation of CD pathology to alleviate CD pathology and symptoms.
Topics: Celiac Disease; Humans; Homeostasis; Candida albicans; Mast Cells; Gastrointestinal Microbiome; Dysbiosis; Candidiasis; Animals; Candida; Intestinal Mucosa
PubMed: 38719750
DOI: 10.26508/lsa.202302441 -
Revista Da Associacao Medica Brasileira... 2024Various studies have reported that certain long non-coding RNA levels are unusually low in the intestines of celiac disease patients, suggesting that this may be...
OBJECTIVE
Various studies have reported that certain long non-coding RNA levels are unusually low in the intestines of celiac disease patients, suggesting that this may be associated with the inflammation observed in celiac disease. Despite these studies, the research aimed at uncovering the potential role of long non-coding RNAs in the pathogenesis of autoimmune diseases like celiac disease remains insufficient. Therefore, in this study, we plan to assess long non-coding RNA polymorphisms associated with autoimmunity in children diagnosed with celiac disease according to the European Society for Paediatric Gastroenterology Hepatology and Nutrition criteria.
METHODS
DNA was isolated from paraffin tissue samples of 88 pediatric celiac disease patients and 74 healthy pediatric individuals. Single-nucleotide polymorphism genotyping of five long non-coding RNA polymorphisms associated with autoimmunity (LINC01934-rs1018326, IL18RAP-rs917997, AP002954.4-rs10892258, UQCRC2P1-rs6441961, and HCG14 rs3135316) was conducted using the TaqMan single-nucleotide polymorphism genotyping assays with the LightCycler 480.
RESULTS
In our study, the genotypic and allelic frequency distribution of LINC01934-rs1018326 and AP002954.4-rs10892258 polymorphisms was found to be statistically significant in the comparison between the two groups (p<0.05). According to the multiple genetic model analyses, the LINC01934-rs1018326 polymorphism was observed to confer a 1.14-fold risk in the recessive model and a 1.2-fold risk in the additive model for pediatric celiac disease. Similarly, the AP002954.4-rs10892258 polymorphism was found to pose a 1.40-fold risk in the dominant model and a 1.7-fold risk in the additive model.
CONCLUSION
Our study results draw attention to the LINC01934-rs1018326 and AP002954.4-rs10892258 polymorphisms in celiac disease and suggest that these polymorphisms may be associated with inflammation in autoimmune diseases like celiac disease.
Topics: Humans; Celiac Disease; RNA, Long Noncoding; Case-Control Studies; Child; Polymorphism, Single Nucleotide; Female; Male; Genetic Predisposition to Disease; Autoimmunity; Child, Preschool; Genotype; Gene Frequency; Adolescent
PubMed: 38716950
DOI: 10.1590/1806-9282.20231490 -
Revista Da Associacao Medica Brasileira... 2024We aimed to examine the effect of remission status on thiol-disulfide homeostasis in celiac patients and thus to indirectly determine the effect of oxidative stress and... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
We aimed to examine the effect of remission status on thiol-disulfide homeostasis in celiac patients and thus to indirectly determine the effect of oxidative stress and inflammation caused by non-compliance with the diet.
METHODS
Between February 2019 and December 2021, 117 patients diagnosed with celiac disease were included in this prospective randomized and controlled study. In addition to routine tests of celiac patients, thiol and disulfide measurements were made from the blood both at the beginning of the study and at the end of the first year.
RESULTS
While 52 of the patients (44.4%) were in remission, 65 patients (55.6%) were not. There was an evident increase in native thiol levels of the patients who were initially not in remission but went into at the end of the first year (347.4±46.7 μmol/L vs. 365.3±44.0 μmol/L; p=0.001). Mean plasma disulfide levels of patients with celiac going into remission became reduced in the first year from the level of 14.5±5.1 μmol/L down to 8.9±4.2 μmol/L (p<0.001). In celiac patients who entered remission, disulfide and anti-tissue transglutaminase immunoglobulin A levels decreased in a correlation (r=0.526; p<0.001).
CONCLUSION
Not being in remission in celiac disease leads to increased oxidative stress, and thiol-disulfide homeostasis is an indirect indicator of this. Additionally, providing remission in celiac patients reduces oxidative stress.
Topics: Humans; Celiac Disease; Oxidative Stress; Female; Male; Disulfides; Prospective Studies; Sulfhydryl Compounds; Adult; Diet, Gluten-Free; Patient Compliance; Remission Induction; Young Adult; Adolescent; Middle Aged; Immunoglobulin A; Transglutaminases
PubMed: 38716937
DOI: 10.1590/1806-9282.20231120 -
Frontiers in Immunology 2024Being defined as an autoimmune, chronic pathology, frequently encountered in any age group, but especially in pediatrics, celiac disease (also called gluten... (Review)
Review
Being defined as an autoimmune, chronic pathology, frequently encountered in any age group, but especially in pediatrics, celiac disease (also called gluten enteropathy), is gaining more and more ground in terms of diagnosis, but also interest in research. The data from the literature of the last decades attest the chameleonic way of its presentation, there may be both classic onset symptoms and atypical symptoms. Given the impact played by celiac disease, especially in the optimal growth and development of children, the current narrative review aims to highlight the atypical presentation methods, intended to guide the clinician towards the inclusion of the pathology in the differential diagnosis scheme. To these we add the summary presentation of the general data and therapeutic lines regarding the underlying condition and the existing comorbidities. In order to place the related information up to date, we performed a literature review of the recent articles published in international databases. We bring forward the current theories and approaches regarding both classic celiac disease and its atypical manifestations. Among these we note mainly constitutional, skin or mucous, bone, neuro-psychic, renal, reproductive injuries, but also disorders of biological constants and association with multiple autoimmunities. Knowing and correlating them with celiac disease is the key to optimal management of patients, thus reducing the subsequent burden of the disease.
Topics: Celiac Disease; Humans; Child; Diagnosis, Differential
PubMed: 38715620
DOI: 10.3389/fimmu.2024.1390755 -
Journal of Atherosclerosis and... Jul 2024Familial hypobetalipoproteinemia (FHBL) 1 is a rare genetic disorder with an autosomal codominant mode of inheritance and is caused by defects in the apolipoprotein... (Review)
Review
Familial hypobetalipoproteinemia (FHBL) 1 is a rare genetic disorder with an autosomal codominant mode of inheritance and is caused by defects in the apolipoprotein (apo) B (APOB) gene that disable lipoprotein formation. ApoB proteins are required for the formation of very low-density lipoproteins (VLDLs), chylomicrons, and their metabolites. VLDLs transport cholesterol and triglycerides from the liver to the peripheral tissues, whereas chylomicrons transport absorbed lipids and fat-soluble vitamins from the intestine. Homozygous or compound heterozygotes of FHBL1 (HoFHBL1) are extremely rare, and defects in APOB impair VLDL and chylomicron secretion, which result in marked hypolipidemia with malabsorption of fat and fat-soluble vitamins, leading to various complications such as growth disorders, acanthocytosis, retinitis pigmentosa, and neuropathy. Heterozygotes of FHBL1 are relatively common and are generally asymptomatic, except for moderate hypolipidemia and possible hepatic steatosis. If left untreated, HoFHBL1 can cause severe complications and disabilities that are pathologically and phenotypically similar to abetalipoproteinemia (ABL) (an autosomal recessive disorder) caused by mutations in the microsomal triglyceride transfer protein (MTTP) gene. Although HoFHBL1 and ABL cannot be distinguished from the clinical manifestations and laboratory findings of the proband, moderate hypolipidemia in first-degree relatives may help diagnose HoFHBL1. There is currently no specific treatment for HoFHBL1. Palliative therapy including high-dose fat-soluble vitamin supplementation may prevent or delay complications. Registry research on HoFHBL1 is currently ongoing to better understand the disease burden and unmet needs of this life-threatening disease with few therapeutic options.
Topics: Humans; Hypobetalipoproteinemias; Disease Management; Hypobetalipoproteinemia, Familial, Apolipoprotein B
PubMed: 38710625
DOI: 10.5551/jat.RV22018 -
PloS One 2024Celiac disease exhibits a higher prevalence among patients with coronavirus disease 2019. However, the potential influence of COVID-19 on celiac disease remains...
Celiac disease exhibits a higher prevalence among patients with coronavirus disease 2019. However, the potential influence of COVID-19 on celiac disease remains uncertain. Considering the significant association between gut microbiota alterations, COVID-19 and celiac disease, the two-step Mendelian randomization method was employed to investigate the genetic causality between COVID-19 and celiac disease, with gut microbiota as the potential mediators. We employed the genome-wide association study to select genetic instrumental variables associated with the exposure. Subsequently, these variables were utilized to evaluate the impact of COVID-19 on the risk of celiac disease and its potential influence on gut microbiota. Employing a two-step Mendelian randomization approach enabled the examination of potential causal relationships, encompassing: 1) the effects of COVID-19 infection, hospitalized COVID-19 and critical COVID-19 on the risk of celiac disease; 2) the influence of gut microbiota on celiac disease; and 3) the mediating impact of the gut microbiota between COVID-19 and the risk of celiac disease. Our findings revealed a significant association between critical COVID-19 and an elevated risk of celiac disease (inverse variance weighted [IVW]: P = 0.035). Furthermore, we observed an inverse correlation between critical COVID-19 and the abundance of Victivallaceae (IVW: P = 0.045). Notably, an increased Victivallaceae abundance exhibits a protective effect against the risk of celiac disease (IVW: P = 0.016). In conclusion, our analysis provides genetic evidence supporting the causal connection between critical COVID-19 and lower Victivallaceae abundance, thereby increasing the risk of celiac disease.
Topics: Celiac Disease; COVID-19; Humans; Mendelian Randomization Analysis; Gastrointestinal Microbiome; Genome-Wide Association Study; SARS-CoV-2
PubMed: 38701071
DOI: 10.1371/journal.pone.0301998 -
Redox Biology Jul 2024In this study, we observed worsening metabolic crosstalk in mouse models with concomitant metabolic disorders such as hyperhomocysteinemia (HHcy), hyperlipidemia, and...
In this study, we observed worsening metabolic crosstalk in mouse models with concomitant metabolic disorders such as hyperhomocysteinemia (HHcy), hyperlipidemia, and hyperglycemia and in human coronary artery disease by analyzing metabolic profiles. We found that HHcy worsening is most sensitive to other metabolic disorders. To identify metabolic genes and metabolites responsible for the worsening metabolic crosstalk, we examined mRNA levels of 324 metabolic genes in Hcy, glucose-related and lipid metabolic systems. We examined Hcy-metabolites (Hcy, SAH and SAM) by LS-ESI-MS/MS in 6 organs (heart, liver, brain, lung, spleen, and kidney) from C57BL/6J mice. Through linear regression analysis of Hcy-metabolites and metabolic gene mRNA levels, we discovered that SAH-responsive genes were responsible for most metabolic changes and all metabolic crosstalk mediated by Serine, Taurine, and G3P. SAH-responsive genes worsen glucose metabolism and cause upper glycolysis activation and lower glycolysis suppression, indicative of the accumulation of glucose/glycogen and G3P, Serine synthesis inhibition, and ATP depletion. Insufficient Serine due to negative correlation of PHGDH with SAH concentration may inhibit the folate cycle and transsulfurarion pathway and consequential reduced antioxidant power, including glutathione, taurine, NADPH, and NAD. Additionally, we identified SAH-activated pathological TG loop as the consequence of increased fatty acid (FA) uptake, FA β-oxidation and Ac-CoA production along with lysosomal damage. We concluded that HHcy is most responsive to other metabolic changes in concomitant metabolic disorders and mediates worsening metabolic crosstalk mainly via SAH-responsive genes, that organ-specific Hcy metabolism determines organ-specific worsening metabolic reprogramming, and that SAH, acetyl-CoA, Serine and Taurine are critical metabolites mediating worsening metabolic crosstalk, redox disturbance, hypomethylation and hyperacetylation linking worsening metabolic reprogramming in metabolic syndrome.
Topics: Animals; Mice; Humans; Metabolic Syndrome; Male; Disease Models, Animal; Hyperhomocysteinemia; Mice, Inbred C57BL; Glucose; Metabolome; Metabolomics; Metabolic Networks and Pathways
PubMed: 38696898
DOI: 10.1016/j.redox.2024.103139 -
The Malaysian Journal of Pathology Apr 2024Persistently elevated thyroid stimulating hormone (TSH) despite levothyroxine (LT4) treatment that exceeds the standard weight-adjusted dose is a common clinical...
INTRODUCTION
Persistently elevated thyroid stimulating hormone (TSH) despite levothyroxine (LT4) treatment that exceeds the standard weight-adjusted dose is a common clinical presentation. This may lead to additional testing for LT4 malabsorption or poor LT4 adherence, the latter of which is challenging to confirm because it is predicated on accurate patient accountability.
CASE REPORT
A 35-year-old lady, post-radioactive iodine therapy for Graves' disease remained euthyroid for a year on oral LT4. Two years later, she was clinically and biochemically hypothyroid despite claiming LT4 compliance. As all laboratory investigations were within the reference range, pseudomalabsorption was suspected and a LT4 absorption test was done. During the test, her free thyroxine increased significantly at 4 hours, reaching a peak of more than 50% from baseline while TSH decreased appropriately from 0 minute to 360 minutes. This was followed by normalisation of TSH with LT4 treatment under direct observation.
DISCUSSION
The LT4 absorption test is a prompt and economical means to rule out true malabsorption, decrease unwarranted subspecialty referrals and validate the weight-adjusted LT4 dose reduction.
Topics: Humans; Adult; Hypothyroidism; Female; Thyroxine; Graves Disease; Thyrotropin
PubMed: 38682851
DOI: No ID Found