Effects of bariatric surgery on hepatic and intestinal lipoprotein particle metabolism in obese, nondiabetic humans.

OBJECTIVE: The dyslipidemia of obesity and other insulin-resistant states is characterized by the elevation of plasma triglyceride-rich lipoproteins (TRL) of both hepatic (apoB-100-containing very low-density lipoprotein) and intestinal (apoB-48-containing chylomicrons) origin. Bariatric surgery is a well-established and effective modality for the treatment of obesity and is associated with improvements in several metabolic abnormalities associated with obesity, including a reduction in plasma triglycerides. Here, we have investigated the effect of bariatric surgery on TRL metabolism. APPROACH AND RESULTS: Twenty-two nondiabetic, obese subjects undergoing bariatric surgery: sleeve gastrectomy (n=12) or gastric bypass (n=10) were studied. Each subject underwent 1 lipoprotein turnover study 1 month before surgery followed by a second study, 6 months after surgery, using established stable isotope enrichment methodology, in constant fed state. TRL-apoB-100 concentration was significantly reduced after sleeve gastrectomy, explained by a decrease (P<0.05) in TRL-apoB-100 production rate and an increase (P<0.05) in TRL-apoB-100 fractional catabolic rate. TRL-apoB-48 concentration was also significantly reduced after sleeve gastrectomy, explained by reduction in TRL-apoB-48 production rate (P<0.05). For gastric bypass, although TRL-apoB-100 concentration declined after surgery (P<0.01), without a significant decline in TRL-apoB-48, there was no significant change in either TRL-apoB-100 or TRL-apoB-48 production rate or fractional catabolic rate. The reduction in TRL-apoB-100 concentration was significantly associated with a reduction in plasma apoC-III in the pooled group of patients undergoing bariatric surgery. CONCLUSIONS: This is the first human lipoprotein kinetic study to explore the mechanism of improvement of TRL metabolism after bariatric surgery. These effects may contribute to the decrease of cardiovascular mortality after surgery. CLINICAL TRIAL REGISTRATION URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01277068.

[Pertinence of Off-label Prescriptions of Innovating and Expensive Drugs in a University Hospital]. / Pertinence des prescriptions « hors AMM/RTU ¼ des molécules onéreuses dans un hôpital universitaire.

OBJECTIVES: Pertinence of off-label prescriptions of innovative and expensive drugs needs a strict scientific appraisal to prevent adverse reaction risks and financial drift. METHODS: Pertinence of such prescriptions has been analyzed in a University Hospital by bibliometric methods. Scientific publications issued from this clinical activity have been also evaluated. RESULTS: Oncology differed from other clinical specialties by a better pertinence in justifying off-label prescriptions (good evidence level in 46% vs. 21%, scientific publications issued from A/B ranked journals: 51% versus 41%). Quality of scientific production from oncologists was also better (publication impact factor [IF] mean: 4.571 versus 2.245). CONCLUSIONS: The better pertinence of off-label prescriptions by oncologists in comparison to others clinicians' ones was mainly due to a shorter field of indications but also to a more efficient organisation such as systematic prescription by seniors, dedicated computerized provider order entry, multidisciplinary team meetings and collaborative culture.

Molecular studies neglect apparently gram-negative populations in the human gut microbiota.

Studying the relationships between gut microbiota, human health, and diseases is a major challenge that generates contradictory results. Most studies draw conclusions about the gut repertoire using a single biased metagenomics approach. We analyzed 16 different stool samples collected from healthy subjects who were from different areas, had metabolic disorders, were immunocompromised, or were treated with antibiotics at the time of the stool collection. The analyses performed included Gram staining, flow cytometry, transmission electron microscopy (TEM), quantitative real-time PCR (qPCR) of the Bacteroidetes and Firmicutes phyla, and pyrosequencing of the 16S rRNA gene amplicons targeting the V6 region. We quantified 10(10) prokaryotes per gram of feces, which is less than was previously described. The Mann-Whitney test revealed that Gram-negative proportions of the prokaryotes obtained by Gram staining, TEM, and pyrosequencing differed according to the analysis used, with Gram-negative prokaryotes yielding median percentages of 70.6%, 31.0%, and 16.4%, respectively. A comparison of TEM and pyrosequencing analyses highlighted a difference of 14.6% in the identification of Gram-negative prokaryotes, and a Spearman test showed a tendency toward correlation, albeit not significant, in the Gram-negative/Gram-positive prokaryote ratio (ρ = 0.3282, P = 0.2146). In contrast, when comparing the qPCR and pyrosequencing results, a significant correlation was found for the Bacteroidetes/Firmicutes ratio (ρ = 0.6057, P = 0.0130). Our study showed that the entire diversity of the human gut microbiota remains unknown because different techniques generate extremely different results. We found that to assess the overall composition of bacterial communities, multiple techniques must be combined. The biases that exist for each technique may be useful in exploring the major discrepancies in molecular studies.

Absence of acute inhibitory effect of insulin on chylomicron production in type 2 diabetes.

OBJECTIVE: Overproduction of intestinally derived apoB-48-containing triglyceride-rich lipoproteins (TRLs) (chylomicrons) has recently been described in type 2 diabetes, as is known for hepatic TRL-apoB-100 (very-low-density lipoprotein) production. Furthermore, insulin acutely inhibits both intestinal and hepatic TRL production, whereas this acute inhibitory effect on very-low-density lipoprotein production is blunted in type 2 diabetes. It is not currently known whether this acute effect on chylomicron production is similarly blunted in humans with type 2 diabetes. METHODS AND RESULTS: We investigated the effect of acute hyperinsulinemia on TRL metabolism in 18 type 2 diabetic men using stable isotope methodology. Each subject underwent 1 control (saline infusion [SAL]) lipoprotein turnover study followed by a second study, under 1 of the 3 following clamp conditions: (1) hyperinsulinemic-euglycemic, (2) hyperinsulinemic-hyperglycemic, or (3) hyperinsulinemic-euglycemic plus intralipid and heparin. TRL-apoB-48 and TRL-apoB-100 production and clearance rates were not different between SAL and clamp and between the different clamp conditions, except for significantly lower TRL-apoB-100 clearance and production rates in hyperinsulinemic-euglycemic plus intralipid and heparin clamp compared with SAL. CONCLUSIONS: This is the first demonstration in individuals with type 2 diabetes that chylomicron production is resistant to the normal acute suppressive effect of insulin. This phenomenon may contribute to the highly prevalent dyslipidemia of type 2 diabetes and potentially to atherosclerosis. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00950209.

Growth hormone level at admission and its evolution during refeeding are predictive of short-term outcome in restrictive anorexia nervosa.

The growth hormone (GH)­insulin-like growth factor-1 (IGF-1) axis is dramatically altered in patients with anorexia nervosa (AN). The aim of the present study was to investigate whether GH and IGF-1 could be predictors of outcome in patients with a restrictive form of AN. Blood levels of GH, IGF-1, adipocytokines, ghrelin, insulin, glucose, and sex and thyroid hormones were measured in eleven women inpatients with AN and in ten healthy women controls. Three stages were compared during refeeding: admission (T0), when BMI reached 16 kg/m2 (T1) and at discharge when BMI reached 17.5 kg/m2 (T2). Clinical status was assessed 6 months after discharge from hospital (T3), and remission was defined by the maintenance of a BMI > or = 17.5 kg/m2. AN patients in remission (AN-R; n 6) had significantly higher GH levels at admission than those who relapsed (AN-NR; n 5) (P < 0.05). During refeeding (delta = T2 - T0), the AN-R group differed from the AN-NR group only by both GH level decrease (P < 0.05) and BMI increase (P < 0.05). In multiple regression analysis, delta GH was associated negatively and significantly and delta leptin and delta body fat mass levels were associated positively and significantly with BMI at T3 and explained 88% of its variability (r2 0.88, P < 0.05). The present study suggests that a low GH level at admission and the absence of its decrease after weight recovery could predict short-term relapse in women suffering from a restrictive form of AN.

[Type 2 autoimmune polyendocrine syndromes (APS-2)]. / Les syndromes polyendocriniens autoimmuns de type 2 (APS-2).

Type 2 autoimmune polyendocrine syndromes (APS-2) are the most frequent disorders associating several organ-specific autoimmune diseases. Their high prevalence is due to the fact that the main manifestations of APS-2, such as thyroidal autoimmunity, type 1 diabetes, autoimmune gastric atrophy and vitiligo, are common diseases. APS-2 represents a clinical model that can serve to help unravel the mechanisms underlying autoimmunity. Diagnosis of APS-2 is a challenge for the clinician, especially in poorly symptomatic forms, and may require systematic screening based on measurement of autoantibodies and functional markers.

Neurologic features and genotype-phenotype correlation in Wolfram syndrome.

OBJECTIVE: Wolfram syndrome (WS) is a rare neurodegenerative disorder characterized by juvenile-onset diabetes mellitus and optic atrophy. Our aim was to describe the nature and the frequency of the neurologic manifestations, which had been poorly studied until now. METHODS: We performed a detailed clinical study with genotype-phenotype correlation in a series of 59 patients with WS. RESULTS: The onset of neurologic symptoms, with a median age of 15 years, was much earlier than previously reported. Cognitive impairment, which was not frequent in previous reports, was observed in 32% of patients with neurologic signs. Like epilepsy, it was mainly found in patients who developed neurologic signs before 15 years of age. In contrast to previous series, we also found malformations of cortical development on magnetic resonance imaging in epileptic children and white matter involvement, including diffuse leukoencephalopathy, in adult patients. We identified 109 mutated alleles corresponding to 56 different mutations of the WFS1 gene, among which 10 were novel. Homozygosity or compound heterozygosity for missense mutation does not seem to influence the age of onset and the occurrence of neurologic complications. However, an interesting point concerns a possible correlation between the location of the mutations and the development of the neurologic manifestations. INTERPRETATION: This series concerns the largest cohort of WS patients reported to date. It illustrates the wide variety of neurologic signs in this syndrome and the necessity of rapid therapeutic coverage to improve the prognosis.

Pulmonary autoimmunity as a feature of autoimmune polyendocrine syndrome type 1 and identification of KCNRG as a bronchial autoantigen.

Patients with autoimmune polyendocrine syndrome type 1 (APS-1) suffer from multiple organ-specific autoimmunity with autoantibodies against target tissue-specific autoantigens. Endocrine and nonendocrine organs such as skin, hair follicles, and liver are targeted by the immune system. Despite sporadic observations of pulmonary symptoms among APS-1 patients, an autoimmune mechanism for pulmonary involvement has not been elucidated. We report here on a subset of APS-1 patients with respiratory symptoms. Eight patients with pulmonary involvement were identified. Severe airway obstruction was found in 4 patients, leading to death in 2. Immunoscreening of a cDNA library using serum samples from a patient with APS-1 and obstructive respiratory symptoms identified a putative potassium channel regulator (KCNRG) as a pulmonary autoantigen. Reactivity to recombinant KCNRG was assessed in 110 APS-1 patients by using immunoprecipitation. Autoantibodies to KCNRG were present in 7 of the 8 patients with respiratory symptoms, but in only 1 of 102 APS-1 patients without respiratory symptoms. Expression of KCNRG messenger RNA and protein was found to be predominantly restricted to the epithelial cells of terminal bronchioles. Autoantibodies to KCNRG, a protein mainly expressed in bronchial epithelium, are strongly associated with pulmonary involvement in APS-1. These findings may facilitate the recognition, diagnosis, characterization, and understanding of the pulmonary manifestations of APS-1.

Clinical phenotype of mitochondrial diabetes due to rare mitochondrial DNA mutations.

OBJECTIVE: While the most frequent mutation responsible for mitochondrial diabetes is the point mutation m.3243 A>G of mitochondrial DNA (mtDNA), few data are available about the role of rare mtDNA mutations in the pathophysiology of diabetes. The main objective of our study was to describe the phenotypic characteristics of patients suffering from diabetes linked to rare mtDNA mutations. RESEARCH DESIGN AND METHODS: We performed a post-hoc analysis of a prospective multicenter cohort of 743 patients with mitochondrial disorder (previously published by the French Network of Mitochondrial Diseases), associated to a literature review of the PubMed database from 1992 to May 2016. We extracted all reported patients with diabetes and identified rare mtDNA mutations and described their clinical and metabolic phenotypes. RESULTS: The 50 identified patients (10 from the princeps study; 40 from the review of the literature) showed a heterogeneous metabolic phenotype in terms of age, symptoms prior to diagnosis, treatments, and associated clinical and biological signs. However, neurological symptoms were more frequent in case of rare mtDNA mutations compared to the classical m.3243 A>G mutation (P=0.024). In contrast, deafness (65% vs. 95%, P=3.7E-5), macular pattern dystrophy (20% vs. 86%, P=1.6E-10) and nephropathy (8% vs. 28%, P=0.018) were significantly less frequent than in case of the classical m.3243 A>G mutation. CONCLUSION: Although no specific metabolic phenotype could be identified suggesting or eliminating implication of rare mtDNA mutations in diabetes, clinical phenotypes featured more frequent neurological signs.

The impact of weight normalization on quality of recovery in anorexia nervosa.

BACKGROUND: There is little agreement on what constitutes remission in anorexia nervosa. OBJECTIVE: This study compared the medical, psychological, and social status of 2 female populations previously treated for anorexia nervosa and differing in their achievement of normal weight. DESIGN: One hundred forty-one patients responded to a questionnaire documenting morphometric parameters, subjective perception of outcome, concerns about body shape and diet, and quality of familial, emotional, and professional life. Two groups were defined according to body mass index (BMI): normal (n = 69) with BMI > or = 18.5 kg/m(2), and subnormal (n = 72) with BMI < 18.5 kg/m(2). In addition, subgroups (21 in each category) were interviewed. An age-matched control population composed of 156 women, either students or Health Services employees, responded to a similar questionnaire. RESULTS: Only a minority of patients assessed themselves as recovered, and there was no statistically significant difference in perception of recovery between normal BMI and subnormal BMI groups (27.5% and 15.3%, respectively). As expected, underweight patients reported significantly more frequent purging behaviors, amenorrhea, recent hospitalization, and prolonged student status. In contrast, there were no significant differences in terms of pregnancy rate, psychiatric comorbidities, social integration, sexual activity, and self-assessment of professional and familial life. In comparison to control subjects, former anorexia patients with normalized BMI more frequently reported vomiting, fear of high-calorie foods, and treatment for depression. CONCLUSIONS: These few long-term advantages observed after BMI normalization suggest that normalization of nutritional status remains an important target in anorexia nervosa. However, the persistence of psychological distress after nutritional recovery confirms that more effective treatments are needed that target long-term psychological recovery.

Hearing impairment in genotyped Wolfram syndrome patients.

OBJECTIVES: Wolfram syndrome is a progressive neurodegenerative syndrome characterized by the features "DIDMOAD" (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). We sought to study the audiometric data of genotyped Wolfram syndrome patients with sensorineural hearing impairment. METHODS: Pure tone threshold data of 23 Wolfram syndrome patients were used for cross-sectional analysis in subgroups (age less than 16 years or between 19 and 25 years, gender, and origin). RESULTS: All subgroups, with 1 exception, showed a fairly similar type of hearing impairment with, on average, thresholds of about 25 dB (range, 0 to 65 dB) at 0.25 to 1 kHz, gently sloping downward to about 60 dB (range, 25 to 95 dB) at 8 kHz. The subgroup of Dutch women, which was excluded from the calculations of the average hearing thresholds, showed a higher degree of hearing impairment. Only the latter subgroup showed progression; however, contrary to the previous longitudinal analysis, progression was not significant in the present cross-sectional analysis, presumably because of the high degree of cross-subject variability. CONCLUSIONS: This unique collection of audiometric data from genotyped Wolfram syndrome patients shows no substantial progression in sensorineural hearing impairment with advancing age, no relation to the types of WFS1 mutations identified, and, with exclusion of the subgroup of Dutch female patients, no significant sex-related differences.

[L-thyroxine pseudomalabsorption: a factitious disease]. / Pseudomalabsorption de L-thyroxine: une forme de pathomimie.

INTRODUCTION: Thyroxine supplementation of patients with hypothyroidism is usually simple. A few patients, however, continue to present elevated TSH levels despite large doses of L-thyroxine. CASE: We report the case of a 71-year-old women who had had a thyroidectomy 10 years earlier and had since been hospitalized repeatedly for profound hypothyroidism. Despite her consistent claims of good adherence to her treatment regimen, we considered the diagnosis of L-thyroxine pseudomalabsorption and confirmed it by thyroid hormone absorption tests. DISCUSSION: L-thyroxine pseudomalabsorption due to concealed poor treatment adherence should be considered after ruling out drug or dietary interference and true organic malabsorption. Diagnosis of this factitious disease can be confirmed by L-thyroxine absorption tests.

Wolfram syndrome in French population: characterization of novel mutations and polymorphisms in the WFS1 gene.

Wolfram syndrome (WS), a rare autosomal recessive neurodegenerative disorder, results in most cases from mutations in the WFS1 gene. In this study, a total of 19 patients with Wolfram syndrome and 36 relatives from 17 families were screened for mutations in the WFS1 gene. WFS1 mutations were identified on both alleles in 16 of 19 patients and on 1 allele of 3 patients, showing that WFS1 is the major gene involved in WS in the french population. We identified 25 different mutations, twelve of which were novel. We found 6 frameshift mutations, 6 nonsense mutations, 6 missense mutations, 6 in-frame deletions, and one new homozygous mutation in the splice donor site of exon 7 (c.861+1G>A) resulting in a frameshift. Most patients were compound heterozygotes. No common founder mutation or mutational hot spot were found in the WFS1 gene. Although most mutations occurred in exon 8, in some cases molecular screening requires analysis of all exons, including the non-coding exon 1. We also identified 3 new polymorphisms. Furthermore, genotype-phenotype correlation suggests that the presence of inactivating mutations on both alleles may be associated with an early onset of diabetes mellitus.

No association between lck gene polymorphisms and protein level in type 1 diabetes.

We previously described a reduced expression of the protein tyrosine kinase Lck in T-cells from type 1 diabetic patients, the origin of which is still unknown. The human lck gene, located on chromosome 1p35-34.3, was evaluated as a candidate susceptibility gene for type 1 diabetes. A molecular scan of the sequence variations in the coding, the relevant promoter, and most of the intronic sequences of the lck gene (representing a total of 10.5 kb fragment) was performed in 187 Caucasian subjects including 91 type 1 diabetic patients and 96 normoglycemic control subjects. We identified 35 sequence variations, including one deletion and 34 single nucleotide polymorphisms (SNPs), 33 of them being new. Four variants were frequent but not significantly associated with diabetes or Lck protein level. Of the SNP variants, 11 were only found within the diabetic population and some were associated with low Lck protein levels. The low frequency of these polymorphisms did not permit any statistically significant correlations with the disease status, suggesting that the lck gene probably does not contribute to genetic susceptibility to type 1 diabetes.

A rare mRNA variant of the human lymphocyte-specific protein tyrosine kinase LCK gene with intron B retention and exon 7 skipping encodes a putative protein with altered SH3-dependent molecular interactions.

A rare mRNA variant of the human lymphocyte-specific protein tyrosine kinase LCK gene that retains intron B and excludes exon 7 (B+7-) due to alternative splicing of the canonical LCK transcripts was identified and characterized. LCK B+7- mRNA is detected in all tested peripheral blood T lymphocytes total RNA samples but is apparently sequestered in the nucleus. The presence of intron B sequence does not disrupt the reading frame and results in the insertion of 58 aminoacids, containing a proline-rich region just upstream of p56lck SH3 domain. This putative isoform encodes an unstable 516 aminoacids protein (LckB+7-) which can be expressed in transfected COS-7 cells. Furthermore in Jurkat T cell extracts, a recombinant intron B plus SH3 p56lck domain fails to interact with some TCR-induced tyrosine phosphorylated polypeptides and known p56lck partners such as Sam68 and c-Cbl. The biological function of this rare messenger remains to be elucidated.

Fasting apoprotein B-48 level and coronary artery disease in a population without frank fasting hypertriglyceridemia.

The aim of this study was to test the hypothesis that fasting apoprotein B-48 level might be a surrogate marker of postprandial lipemia in evaluating the risk of coronary artery disease (CAD) in a population without frank abnormality in fasting lipid profile. One hundred twenty-three patients tested by coronary angiography were selected on the criteria of absence of treatment with hypolipidemic drugs, obvious hypertriglyceridemia (>2.85 mmol/L), or other conditions that may interfere with lipoprotein metabolism except diabetes. CAD was defined by more than 50% narrowing of vessel lumen, and its severity is determined by the number of arteries involved. Fasting apoprotein B-48 was measured by a competitive enzyme-linked immunosorbent assay method. There was no difference in fasting apoprotein B-48 levels between the groups with and without CAD (0.123+/-0.096 vs 0.136+/-0.125 microg/mL, respectively), whatever the sex or whether with or without diabetes. The apoprotein B-48 level was not related to the presence or the severity of CAD. There was also no correlation between fasting apoprotein B-48 levels and age, sex, body mass index, and usual fasting lipid parameters in both patients with and without angiographically proven CAD. Finally, among the features of metabolic syndrome, apoprotein B-48 was correlated with fasting triglyceride levels (r=0.357, P<.01) only. In conclusion, the present study shows that in the absence of any major fasting abnormality in plasma lipid parameters, fasting apoprotein B-48 level, which has been associated with postprandial hyperlipidemia, does not predict the risk of CAD.

A randomized trial of low-protein diet in type 1 and in type 2 diabetes mellitus patients with incipient and overt nephropathy.

OBJECTIVE: The efficacy of a low-protein diet in the secondary prevention of diabetic nephropathy is not established in patients with type 1 or type 2 diabetes mellitus. To determine whether a low-protein diet slows the decrease in glomerular filtration rate (GFR) and decreases the albumin excretion rate (AER) in diabetic patients with incipient and overt nephropathy, we performed a 2-year prospective, randomized controlled trial comparing the effects of a low-protein diet (0.8 g/kg/day) with a usual-protein diet. SETTING AND PATIENTS: The study was conducted in a University hospital and included 63 type 1 and type 2 diabetic patients with either incipient or overt nephropathy and mild renal failure (prestudy GFR, 80 +/- 20 mL/min). The primary outcome measures were decreased in GFR and 24-hour AER. RESULTS: In the low-protein-diet group, patients were younger (52 +/- 12 versus 63 +/- 9 years old) and more often were type 2 diabetic. During the follow-up period, according to dietary records the low-protein-diet group consumed 16% +/- 3% of total caloric intakes as compared with 19% +/- 4% in the usual-protein-diet group (P < .02), but 24-hour urinary urea excretions did not differ between the two groups. The 2-year GFR decrease was 7 +/- 11 mL/min in the low-protein-diet group and 5 +/- 15 mL/min in the usual-protein-diet group (P = not significant). AER did not increase significantly in the two diet groups during the follow-up period. Blood pressure and glycemic control were similar in the two groups all along the study. The decrease in GFR and AER were also similar in 6 compliant patients according to dietary records and to 24-hour urinary urea excretions from the low-protein-diet group and in 12 patients from the usual-protein-diet group. CONCLUSIONS: A 2-year low-protein diet did not alter the course of GFR or of AER in diabetic patients with incipient or overt nephropathy receiving renin-angiotensin blockers with strict blood pressure control.

Disruption of services in an internal medicine unit due to a nosocomial influenza outbreak.

OBJECTIVE: To describe a nosocomial influenza A outbreak, how it was managed, what impact it had on subsequent delivery of health care, and the additional charges attributable to it DESIGN: Prospective cohort study and microbiological investigation. SETTING: One internal medicine unit in an acute care, university-affiliated hospital. PARTICIPANTS: Twenty-three patients and 22 staff members from February 28 to March 6, 1999. RESULTS: Attack rates were 41% (9 of 22) among patients and 23% (5 of 22) among staff members, with 3 of 14 cases being classified as "certain." The influenza virus isolates were typed as A/SYDNEY/5/97 (H3N2). The index case was a patient who shared a room with the first nosocomial case. Vaccination rates for influenza virus were 43% (10 of 23) among patients and 36% (8 of 22) among staff members. The outbreak resulted in staff members' taking 14 person-days of sick leave. Furthermore, 8 scheduled admissions were postponed and all emergency admissions were suspended for 11 days. Hospital charges attributable to the influenza outbreak totaled $34,179 and the average extra charge per infected patient was $3,798. CONCLUSIONS: Nosocomial influenza outbreaks increase charges and alter the quality of care delivered in acute care settings. Strategies for their prevention need to be evaluated in acute care settings.

Culturomics and pyrosequencing evidence of the reduction in gut microbiota diversity in patients with broad-spectrum antibiotics.

The human gut flora is currently widely characterised using molecular techniques. Microbial culturomics (large-scale culture conditions with identification of colonies using MALDI-TOF or 16S rRNA) is part of the rebirth of bacterial culture that was initiated by environmental microbiologists for the design of axenic culture for intracellular bacteria in clinical microbiology. Culturomics was performed on four stool samples from patients treated with large-scale antibiotics to assess the diversity of their gut flora in comparison with other culture-dependent studies. Pyrosequencing of the V6 region was also performed and was compared with a control group. Gut richness was also estimated by bacterial counting after microscopic observation. In total, 77 culture conditions were tested and 32,000 different colonies were generated; 190 bacterial species were identified, with 9 species that had not been isolated from the human gut before this study, 7 newly described in humans and 8 completely new species. A dramatic reduction in diversity was observed for two of the four stool samples for which antibiotic treatment was prolonged and uninterrupted. The total number of bacteria was generally preserved, suggesting that the original population was replaced but was sustained in size. Discordances between culture and pyrosequencing biodiversity biomarkers highlight the depth of bias of molecular studies. Stool samples studied showed a dramatic reduction in bacterial diversity. Considering the variable antibiotic concentration in the gut, this reduction in the number of species is possibly linked to the production of bacteriocin in the upper digestive tract by specific bacteria, such as Lactobacillus spp.

Can stress induce dysimmune dysthyroidism?

Hyperthyroidism due to Graves' disease is autoimmune in origin. The initiation of dysimmunity responsible for the disease is still poorly understood. Numerous population studies show that genetic factors have a major role, but the environment and any kind of stress also contribute to the onset of the disease. There remains the recurring question for medical experts of the accountability of stress in the onset of Graves' disease. To date, it is impossible to establish a direct link between this disease and a specific stress. The relationship can only be hypothetical, indirect and partial.