Direct oral and fiber-derived butyrate supplementation as an anti-obesity treatment via different targets.

BACKGROUND & AIMS: Butyric (one of the short-chain fatty acids), a major byproduct of the fermentation of non-digestible carbohydrates (e.g. fiber), is supposed to have anti-obesity and anti-inflammatory properties. However, butyrate's potential and mechanism in preventing obesity and the efficient form of administration remain to be clarified. METHODS: Hence, we studied the effect of oral supplementation with 5% (w/w) sodium butyrate and 4% (w/w) ß-glucan (fiber) on young male mice (C57BL/6J) with high-fat diet-induced obesity (HFD: 60 kcal% of fat + 1% of cholesterol). Six weeks old mice were fed diets based on HFD or control (AIN-93G) diet with/without supplements for 4 weeks. The unique, interdisciplinary approach combining several Raman-based techniques (including Raman microscopy and fiber optic Raman spectroscopy) and next-generation sequencing was used to ex vivo analyze various depots of the adipose tissue (white, brown, perivascular) and gut microbiome, respectively. RESULTS: The findings demonstrate that sodium butyrate more effectively prevent the pathological increase in body weight caused by elevated saturated fatty acids influx linked to a HFD in comparison to ß-glucan, thereby entirely inhibiting diet-induced obesity. Moreover, butyrate significantly affects the white adipose tissue (WAT) reducing the epididymal WAT mass in comparison to HFD without supplements, and decreasing lipid saturation in the epididymal WAT and perivascular adipose tissue of the thoracic aorta. Contrarily, ß-glucan significantly changes the composition and diversity of the gut microbiome, reversing the HFD effect, but shows no effect on the epididymal WAT mass and therefore the weight gain inhibition is not as effective as with sodium butyrate. CONCLUSIONS: Here, oral supplementation with sodium butyrate and ß-glucan (fiber) has been proven to have an anti-obesity effect through two different targets. Administration-dependent effects that butyrate imposes on the adipose tissue (oral administration) and microbiome (fiber-derived) make it a promising candidate for the personalized treatment of obesity.

Reduction in the Free Androgen Index in Overweight Women After Sixty Days of a Low Glycemic Diet.

BACKGROUND: Hyperandrogenism is among the most common endocrine disorders in women. Clinically, it manifests as hirsutism, acne, and alopecia. A healthy lifestyle, including nutritious dietary patterns and physical activity, may influence the clinical manifestation of the disease. This study determined the effect of a low-glycemic index anti-inflammatory diet on testosterone levels and sex hormone-binding globulin (SHBG) and clinical symptoms in hyperandrogenic women at their reproductive age. METHODS: The study included 44 overweight and obese women diagnosed with hyperandrogenism. The anthropometrics (weight, height, body mass index, waist circumference, hip circumference), physical activity, and dietary habits were assessed using valid questionnaires, scales, stadiometer, and tape meter. The significant p-value was <0.001. Serum testosterone and SHBG levels were measured using automated immunoassay instruments. RESULTS: The intervention based on a low-glycemic index diet with anti-inflammatory elements and slight energy deficit decreased total testosterone levels (p<0.003), increased SHBG levels (p<0.001), and decreased the free androgen index (FAI; p<0.001). Post-intervention, overall well-being was much higher than in the pre-intervention period (p<0.001), and stress was diminished (p<0.001). Western nutritional patterns positively correlate with clinical hyperandrogenism progression, whereas several factors of the low-glycemic index diet with anti-inflammatory elements and slight energy deficit positively associate with reduced clinical hyperandrogenism symptoms. CONCLUSIONS: In overweight and obese women, proper selection of diet, introduction of moderate physical activity, and reduction in weight, stress factors, and alcohol consumption translate into several positive effects, including reduced FAI and symptoms such as acne, hirsutism, menstrual disorders, and infertility.

Duodenal microbiota and weight-loss following sleeve gastrectomy and Roux-en-Y gastric bypass - a pilot study.

BACKGROUND: Bariatric surgery is the most effective method of morbid obesity treatment. Microbiota has many functions in human body and many of them remain to be unknown. The aim of this study was to establish if the composition of duodenal microbiota influences success rate of bariatric surgery. METHODS: It was a prospective cohort study. The data concerning demographics and comorbidities was collected perioperatively. The duodenal biopsies were collected prior to surgery with the gastroscope. Then DNA analysis was conducted. The data connected to the operation outcomes was gathered after 6 and 12 months after surgery. RESULTS: Overall, 32 patients were included and divided into two groups (successful - group 1 and unsuccessful - group 0) based on percentage excess weight loss after 6 months were created. The Total Actual Abundance was higher in group 0. In group 0 there was a significantly higher amount of Roseburia and Arthrobacter (p = 0.024, p = 0.027, respectively). Genus LDA effect size analysis showed Prevotella, Megasphaera and Pseudorhodobacter in group 1 to be significant. Whereas abundance of Roseburia and Arthrobacter were significant in group 0. CONCLUSIONS: Duodenal microbiota composition may be a prognostic factor for the success of the bariatric surgery but further research on the larger group is needed.

Changes in the gut mycobiome in pediatric patients in relation to the clinical activity of Crohn's disease.

BACKGROUND: Numerous studies have shown that in Crohn's disease (CD), the gut microbiota is of great importance in the induction and maintenance of inflammation in the gastrointestinal tract. Until recently, studies have focused almost exclusively on bacteria in the gut. Lately, more attention has been paid to the role of intestinal fungi. AIM: To study the gut mycobiome analysis of pediatric patients with CD (in different stages of disease activity) compared to healthy children. METHODS: Fecal samples were collected from patients: With active, newly diagnosed CD (n = 50); active but previously diagnosed and treated CD (n = 16); non-active CD and who were in clinical remission (n = 39) and from healthy volunteers (n = 40). Fungal DNA was isolated from the samples. Next, next generation sequencing (MiSeq, Illumina) was performed. The composition of mycobiota was correlated with clinical and blood parameters. RESULTS: Candida spp. were overrepresented in CD patients, while in the control group, the most abundant genus was Saccharomyces. In CD patients, the percentage of Malassezia was almost twice that of the control (P < 0.05). In active CD patients, we documented a higher abundance of Debaryomyces hansenii (D. hansenii) compared to the non-active CD and control (P < 0.05) groups. Moreover, statistically significant changes in the abundance of Mycosphaerella, Rhodotorula, and Microidium were observed. The analyses at the species level and linear discriminant analysis showed that in each group it was possible to distinguish a specific species characteristic of a given patient population. Moreover, we have documented statistically significant correlations between: D. hansenii and patient age (negative); C. zeylanoides and patient age (positive); C. dubliniensis and calprotectin (positive); C. sake and calprotectin (positive); and C. tropicalis and pediatric CD activity index (PCDAI) (positive). CONCLUSION: Mycobiome changes in CD patients, and the positive correlation of some species with calprotectin or PCDAI, give strong evidence that fungi may be of key importance in the development of CD.

miRNA Signature of Urine Extracellular Vesicles Shows the Involvement of Inflammatory and Apoptotic Processes in Diabetic Chronic Kidney Disease.

BACKGROUND: The aim of this study was to investigate the role of urine-derived extracellular vesicles (uEVs) in diabetic kidney disease (DKD) in patients diagnosed with type 2 diabetes mellitus (T2DM). METHODS: UEVs were characterized by size distribution and microRNA content by next-generation small RNA sequencing and quantitative reverse transcription PCR. RESULTS: A subset of sixteen miRNAs enriched in T2DM patients with DKD, including hsa-miR-514a-5p, hsa-miR­451a, hsa-miR-126-3p, hsa-miR-214, or hsa-miR­503 was identified. Eight miRNAs as hsa-miR-21-3p, hsa-miR-4792, hsa-miR­375, hsa-miR-1268a, hsa-miR-501-5p, or hsa-miR-582 were downregulated. Prediction of potential target genes and pathway enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) confirmed possible functions related to cellular processes such as apoptosis, inflammation, and tissue remodeling, that promote diabetic complications, such as DKD. Among them, hsa-miR-375, hsa-miR-503, and hsa-miR-451a make important contribution. Additionally, downregulated hsa-miR-582-5p has not been reported so far in any diabetes-related pathways. CONCLUSIONS: This study revealed the most significant miRNAs in uEVs of patients with T2DM. However, as this is a bioinformatic prediction that we performed based on the putative targets of the identified miRNAs. Thus, further in vitro functional studies are needed to confirm our findings. Knowing the fact that EVs are crucial in transferring miRNAs, there is a great need toto discover their involvement in the pathomechanism of T2DM-related kidney disease.

New insights into diversity of the upper respiratory tract microbiota and its relationship with SARS-CoV-2 viral load in the nasopharyngeal epithelial cells in patients with COVID-19.

INTRODUCTION: The effects of SARS­CoV­2 infection on the composition of the upper respiratory tract (URT) microbiota are yet to be established, and more attention to this topic is needed. OBJECTIVES: The study aimed to assess the bacterial profile and the possible association between the URT microbiota composition and the SARS­CoV­2 viral load. PATIENTS AND METHODS: Nasopharyngeal swabs were taken from 60 adult patients with SARS­CoV­2 infection who were divided into 3 groups based on the quantification cycle (Cq) value in the quantitative polymerase chain reaction test: group I (n = 20), Cq lower than or equal to 31 (high replication rate); group II (n = 20), Cq greater than 31 and lower than 38 (low replication rate), and group III (n = 20), Cq higher than or equal to 38 (virus eliminated from the nasopharyngeal epithelial cells). The obtained genetic libraries of 16S rRNA were sequenced and taxonomic diversity profiling was performed to determine the α- and ß­biodiversity in each group. RESULTS: A significantly lower abundance of Prevotella species was noted in group I, as compared with groups II and III. Akkermansia muciniphila, Faecalibacterium prausnitzii, Fusicatenibacterium saccharivorans, and Bacteroides dorei abundance was characteristic of and significantly greater in group I than in groups II and III. Overall, the microbiota composition was the most diverse in group I, whereas groups II and III were more homogenous in terms of taxonomic diversity. CONCLUSIONS: The arbitrary division of patients according to the SARS­CoV­2 viral load was reflected in diverse composition of their bacterial microbiota, which implies an association between these 2 factors. The patients with a low viral replication rate and those who eliminated the virus from the epithelial cells belonged to a group with a less diverse microbiota community than the patients with a high viral replication rate.

"Impact of preoperative gastrointestinal microbiota on weight-loss after Roux-en-Y gastric bypass: a pilot study ".

BACKGROUND INFORMATION: In recent years the composition of gut microbiome has been linked to development of several diseases. The goal of the following study was to establish whether it is connected to the outcome of bariatric surgery. The objective was to analyze the oral and gut microbiota of patients suffering from morbid obesity who underwent laparoscopic Roux-en-Y gastric bypass (LRYGB). METHODS: The following is a prospective cohort study that was conducted between November 2018 and June 2019. Participants underwent LRYGB surgery. Patients then were assigned to group 1- success (surgical participants who achieved a percentage of excess weight loss [%EWL] >50%), group 2 (surgical participants who achieved a %EWL <50%). The follow up to establish the %EWL was conducted 6 months after the surgery. Before surgery, oral swabs were obtained, and stool samples were provided. The endpoint was the composition of the gut microbiota. RESULTS: Group 1 consisted of 4 participants; group 2 consisted of 2 participants. No participants were lost to follow-up during the study. Participants in group 1 had an oral microbiota that was enriched in the family Tissirelia of the phylum firmicutes. Gut microbiome of patients in group 1 was enriched with with Tanerella of the Bacteroidetes phylum. Group 2 did not present enriched microbiota by any of the analyzed organisms. Gut microbiota was enriched by deltaprotebacteria class (phylum Proteobacteria), bernesiellaceae of the phylum Bacteroidetes.

Comparison of iSeq and MiSeq as the two platforms for 16S rRNA sequencing in the study of the gut of rat microbiome.

Amplicon-based next-generation sequencing (NGS) of the 16S ribosomal RNA (16S) regions is a culture-free method used to identify and analyze Procaryota occurring within a given sample. The prokaryotic 16S rRNA gene contains conserved regions and nine variable regions (V1-V9) frequently used for phylogenetic classification of genus or species in diverse microbial populations. This work compares the accuracy and efficacy of two platforms, iSeq and MiSeq from Illumina, used in sequencing 16S rRNA. The most important similarities and differences of 16S microbiome sequencing in 20 fecal rat samples were described. Genetic libraries were prepared according to 16S Metagenomic Sequencing Library Preparation (Illumina) for the V3 and V4 regions of the 16S. The species richness obtained using iSeq technology was lower compared to MiSeq. At the second taxonomy level (L2), the abundance of taxa was comparable for both platforms. At the L7, the taxa abundance was significantly different, and the number of taxa was higher for the MiSeq. The alpha diversity was lower for iSeq than for MiSeq, starting from the order to the species level. The beta diversity estimation revealed statistically significant differences in microbiota diversity starting from the class level to the species level in samples sequenced on two investigated platforms. This work disclosed that the iSeq platform could be used to evaluate the bacterial profile of the samples to characterize the overall profile. The MiSeq System seems to be better for a detailed analysis of the differences in the microbiota composition. KEY POINTS: • iSeq platform allows to shorten the sequencing time three times compared to the MiSeq. • iSeq can only be used for an initial and quick microbiome assessment. • MiSeq is better for a detailed analysis of the differences in the microbiota composition.

Changes in the Composition of Oral and Intestinal Microbiota After Sleeve Gastrectomy and Roux-En-Y Gastric Bypass and Their Impact on Outcomes of Bariatric Surgery.

BACKGROUND: We aimed to assess the changes in composition of bacterial microbiota at two levels of the digestive tract: oral cavity and large intestine in patients 6 months after bariatric surgery. METHODS: This was a prospective cohort study including patients undergoing bariatric surgery. Before surgery and 6 months after the procedure, oral swabs were obtained and stool samples were provided. Our endpoint was the analysis of the differences in compositions of oral and fecal microbiota prior and after the surgical treatment of obesity. RESULTS: Bacteria from phylum Bacteroidetes seemed to increase in abundance in both the oral cavity and the large intestine 6 months after surgery among patients undergoing bariatric surgery. The subgroup analysis we conducted based on the volume of weight-loss revealed that patients achieving at least 50% of excess weight loss present similar results to the entire study group. Patients with less favorable outcomes presented an increase in the population of bacteria from phylum Fusobacteria and a decrease of phylum Firmicutes in oral cavity. CONCLUSION: Intestinal microbiota among these patients underwent similar changes in composition to the rest of the study group. Bariatric surgery introduces a significant change in composition of oral and intestinal microbiota.

The Role of the Western Diet and Oral Microbiota in Parkinson's Disease.

The type of diet not only affects the composition of the oral microflora but is also one of the more critical factors associated with an increased risk of Parkinson's disease, PD. This study compared diet preferences and oral microbiota profiles in patients with PD vs. healthy controls. This study compared the oral microbiota composition of 59 patients with PD and 108 healthy controls (without neurodegeneration) using 16S rRNA gene amplicon sequencing. According to results, oral microbiota in patients with PD is different compared from healthy controls. In particular, decreased abundance of Proteobacteria, Pastescibacteria, and Tenercutes was observed. The oral cavity of patients with PD was characterized by the high relative abundance of bacteria from the genera Prevotella, Streptococcus, and Lactobaccillus. There were also differences in food preferences between patients with PD and healthy controls, which revealed significantly higher intake of margarine, fish, red meat, cereals products, avocado, and olives in the patients with PD relative to healthy controls. Strong positive and negative correlations between specific food products and microbial taxa were identified.

The Role of Single Nucleotide Polymorphisms of Monoamine Oxidase B, Dopamine D2 Receptor, and DOPA Decarboxylase Receptors Among Patients Treated for Parkinson's Disease.

This study aimed to investigate the association between selected variants of genes related to dopamine metabolism pathways and the risk of and progression of Parkinson's disease (PD). This prospective cohort study was conducted in one academic teaching hospital. The study was conducted on 126 patients diagnosed with idiopathic Parkinson's disease. Blood samples were collected to conduct a genotyping of MAOB, DRD1, DRD2, and DDC genes. Genotype and allele frequencies of MAOB (rs1799836) variants were not associated with the course of PD. Genotype and allele frequencies of DRD2 (rs2283265) variants were associated with risk of dementia (p = 0.001) and resulted in parts II and III of the UPDRS scale (p = 0.001). Genotype and allele frequencies of DRD2 (rs1076560) variants were associated with risk of dementia (p = 0.001) and resulted in parts II and III of the UPDRS scale (p = 0.001). Genotype and allele frequencies of DDC (rs921451) variants were not associated with the course of PD.

Mutation search within monogenic diabetes genes in Polish patients with long-term type 1 diabetes and preserved kidney function.

INTRODUCTION: Some patients with type 1 diabetes (T1DM) are free from advanced complications despite long­standing disease. These patients may be carriers of gene mutations responsible for maturity­onset diabetes of the young and may have been misdiagnosed with T1DM. OBJECTIVES: We aimed to determine the clinical characteristics of patients with long­term T1DM, without advanced microvascular complications, and with well­preserved kidney function. A search for mutations in monogenic diabetes genes was performed. PATIENTS AND METHODS: Patients were recruited at 2 Polish university centers based on the following criteria: T1DM duration of 40 years or longer and absence of advanced complications defined as chronic kidney disease (estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m2 ), overt proteinuria, blindness, and diabetic foot syndrome. Mutations in the 7 most frequent monogenic diabetes genes were identified using next­generation sequencing. RESULTS: We enrolled 45 patients with T1DM (mean [SD] age at examination, 59.2 [8.0] years; mean [SD] age at T1DM diagnosis, 14.6 [6.7] years). Mean (SD) hemoglobin A1c levels were 7.6% (1.4%); daily insulin dose, 0.48 (0.17) U/kg; high­density lipoprotein (HDL) cholesterol levels, 1.9 (0.6) mmol/l; body mass index (BMI), 26.4 (5.0) kg/m2 ; and eGFR, 82.2 (12.1) ml/min/1.73 m2 . Albuminuria and retinopathy were reported in 7 and 39 patients, respectively. We were not able to assign a causative role to any of 10 genetic variants identified by next­generation sequencing in this cohort. CONCLUSIONS: Patients with long­term T1DM and preserved kidney function have good glycemic control, elevated HDL cholesterol levels, low insulin requirements, near ­normal BMI, and a rare occurrence of mutations in monogenic diabetes genes.

Characteristics of the gut microbiome in esports players compared with those in physical education students and professional athletes.

Introduction: Esports is a category of competitive video games that, in many aspects, may be similar to traditional sports; however, the gut microbiota composition of players has not been yet studied. Materials and methods: Here, we investigated the composition and function of the gut microbiota, as well as short chain fatty acids (SCFAs), and amino acids, in a group of 109 well-characterized Polish male esports players. The results were compared with two reference groups: 25 endurance athletes and 36 healthy students of physical education. DNA and metabolites isolated from fecal samples were analyzed using shotgun metagenomic sequencing and mass spectrometry, respectively. Physical activity and nutritional measures were evaluated by questionnaire. Results: Although anthropometric, physical activity and nutritional measures differentiated esports players from students, there were no differences in bacterial diversity, the Bacteroidetes/Firmicutes ratio, the composition of enterotype clusters, metagenome functional content, or SCFA concentrations. However, there were significant differences between esports players and students with respect to nine bacterial species and nine amino acids. By contrast, all of the above-mentioned measures differentiated professional athletes from esports players and students, with 45 bacteria differentiating professional athletes from the former and 31 from the latter. The only species differentiating all three experimental groups was Parabacteroides distasonis, showing the lowest and highest abundance in esports players and athletes, respectively. Conclusion: Our study confirms the marked impact of intense exercise training on gut microbial structure and function. Differences in lifestyle and dietary habits between esports players and physical education students appear to not have a major effect on the gut microbiota.

Differences in the Composition of Gut Microbiota between Patients with Parkinson's Disease and Healthy Controls: A Cohort Study.

Gut microbiome and colonic inflammation can be associated with the predisposition and progression of Parkinson's disease (PD). The presented study aimed to compare gastrointestinal microbiota composition between patients diagnosed with PD and treated only with Levodopa to healthy controls. In this prospective study, patients were recruited in 1 academic hospital from July 2019 to July 2020. The detailed demographic data and medical history were collected using a set of questionnaires. Fecal samples were obtained from all participants. Next-Generation Sequencing was used to assess the microbiota composition. The endpoint was the difference in composition of the gut microbiota. In this study, we enrolled 27 hospitalized PD patients with well-controlled symptoms. The control group included 44 healthy subjects matched for age. Among PD patients, our results presented a higher abundance of Bacteroides phylum, class Corynebacteria among phylum Actinobacteria, class Deltaproteobacteria among phylum Proteobacteria, and genera such as Butyricimonas, Robinsoniella, and Flavonifractor. The species Akkermansia muciniphila, Eubacterium biforme, and Parabacteroides merdae were identified as more common in the gut microbiota of PD patients. In conclusion, the patients diagnosed with PD have significantly different gut microbiota profiles in comparison with healthy controls.

Non-IgE Mediated Hypersensitivity to Food Products or Food Intolerance-Problems of Appropriate Diagnostics.

The diagnosis of food intolerance is tricky due to the different etiologies of adverse reactions. There is also a lack of clear rules for interpreting alternative tests used to diagnose these problems. The analyses of IgG4 concentration in serum or cytotoxic tests became the basis of elimination diets. However, it can result in nutritional deficiencies and loss of tolerance to eliminated foods. Our study aimed to assess the necessity of food elimination in four cases with food intolerance symptoms based on alternative diagnostic tests. Four patients without food allergies, who manifested diverse clinical symptoms after food, were presented due to the following factors: clinical history, diagnostic tests, elimination diet, and filaggrin gene (FLG) mutation. It was found that higher IgG4 levels against foods and higher cytotoxic test values are not clinically relevant in each of the studied individuals. They should not be decisive for the elimination of food products. The study of FLG-SNVs revealed the association of some clinical symptoms in patients with hypersensitivity to several food allergens and reported genetic variants in the FLG gene.

Differences in Compositions of Oral and Fecal Microbiota between Patients with Obesity and Controls.

Background and Objectives: The aim of this study was to compare the differences in compositions of oral and fecal bacterial microbiota between patients with morbid obesity and normal-weight controls. Material and Methods: This was a prospective cohort study. The study included group 1 (patients with BMI ≥ 40 kg/m2) and group 2 (patients with BMI from 18.5 to 24.9 kg/m2). Our endpoint was the analysis of the differences in compositions of oral and fecal microbiota between the groups. Oral swabs and fecal samples were collected from the patients. The analysis of microbiota was conducted using next-generation sequencing. Results: Overall, the study included 96 patients; 52 (54.2%) were included in group 1, 44 (39.8%)-in group 2. In group 1, oral microbiota included significantly more bacteria from genera Veillonella, Oribacterium and Soonwooa, whereas, in group 2, Streptobacillus, Parvimonas and Rothia were more common. Fecal microbiota in group 1 included more Bacteroides, Odoribacter and Blautia and group 2 was more abundant in Ruminococcus, Christensenella and Faecalibacterium. Conclusions: Both oral and fecal gastrointestinal microbiota differs significantly among patients with severe obesity and lean individuals.

Relationship between bariatric surgery outcomes and the preoperative gastrointestinal microbiota: a cohort study.

BACKGROUND: The composition of the gastrointestinal microbiota is associated with obesity. We hypothesized that the gut microbiota influences the outcomes of bariatric surgery. OBJECTIVES: We aimed to analyze using oral swabs and stool samples the microbiota of patients with morbid obesity who were undergoing laparoscopic sleeve gastrectomy (SG). SETTING: A university hospital in Poland. METHODS: This prospective cohort study was conducted between November 2018 and June 2019. Participants underwent SG or no surgery (controls). Results were then analyzed as a group 1 (surgical participants who achieved a percentage of excess weight loss [%EWL] >50%), group 2 (surgical participants who achieved a %EWL <50%), and group 3 (nonsurgical controls). %EWL was measured 6 months following surgery. Before surgery, oral swabs were obtained and stool samples were provided. The endpoint was the composition of the gut microbiota. RESULTS: Group 1 comprised 19 participants, group 2 comprised 11 participants, and group 3 comprised 16 participants. No participants were lost to follow-up during the study. Participants in group 1 had an oral microbiota that was enriched in the phyla Proteobacteria, and Bacteroidetes. Their intestinal microbiota was enriched in the Proteobacteria. In contrast, the oral microbiota of group 2 was enriched in the Actinobacteria and the intestinal microbiota was enriched in the phyla Bacteroidetes and Firmicutes. CONCLUSIONS: The compositions of the microbiota of the oral cavity and large intestine are related to the weight loss achieved following SG.

Does Postoperative Oral and Intestinal Microbiota Correlate with the Weight-Loss Following Bariatric Surgery?-A Cohort Study.

The composition of the gastrointestinal microbiota is associated with obesity. The aim of this study was to verify if, six months after bariatric surgery, patients who achieve satisfying weight-loss after sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) have a different composition of oral and intestinal microbiota in comparison with those who do not. This prospective cohort study was conducted between November 2018 and November 2020. Participants underwent either SG or RYGB and were allocated into: Group 1-participants who achieved a percentage of excess weight loss (%EWL) of ≥ 50%, and Group 2-patients with %EWL of < 50%. The %EWL was measured 6 months following surgery. At this time, oral swabs were obtained and stool samples were provided. The endpoint was the composition of the gut microbiota. Group 1 comprised 20 participants and Group 2 comprised 11 participants. Group 1 had oral microbiota more abundant in phylum Fusobacteria and intestinal microbiota more abundant in phylum Firmicutes. Group 2 had oral microbiota was more enriched in phylum Actinobacteria and intestinal microbiota was more enriched in phylum Bacteroidetes. The compositions of the microbiota of the oral cavity and large intestine 6 months after bariatric surgery are related to the weight-loss.

A case of mucopolysaccharidosis type VI in a polish family. Importance of genetic testing and genotype-phenotype relationship in the diagnosis of mucopolysaccharidosis.

BACKGROUND AND OBJECTIVES: Mucopolysaccharidosis type VI (MPS VI) is a rare, autosomal recessive lysosomal storage disorder caused by deficient enzymatic activity of N-acetyl galactosamine-4-sulphatase, which is caused by mutations in the arylsulphatase B (ARSB) gene. To date, 163 different types of mutations in the ARSB have been reported. However, the full mutation spectrum in the MPS VI phenotype is still not known. The aim of this study was to perform molecular testing of the ARSB gene in the patient and his family members to confirm MPS VI. METHODS: Molecular characterisation of the ARSB gene was performed using Sanger sequencing. We studied a child suspected of having MPS VI and 16 other relatives. RESULTS: We identified a C-to-T transition resulting in an exchange of the Arg codon 160 for a premature stop codon (R160*, in exon 2). The transition was in CpG dinucleotides. INTERPRETATION AND CONCLUSIONS: The study provided some insights into the genotype-phenotype relationship in MPS VI and the importance of genetic testing when diagnosing MPS, which is not a mandatory test for the diagnosis and only very occasionally performed. Additionally, we present here the history of a family with confirmed MPS VI, which is extremely rare especially in south-eastern Poland. What is more, the position where the mutation is located is very interesting because it is the region of CpG, which is the site of the methylation process. Thus, this opens the possibility of a new approach indicating the involvement of an epigenetic mechanism that should be examined in the context of the pathomechanism of MPS.

The utility of MODY Probability Calculator in probands of families with early-onset autosomal dominant diabetes from Poland.

BACKGROUND: Maturity-onset diabetes of the young (MODY) accounts for 1-2% of all diabetes cases. Unfortunately, circa 90% of MODY cases are misdiagnosed as type 1 or type 2 diabetes. A proper genetic diagnosis based on automatic sequencing is crucial for the use of a tailored treatment. However, this method is still expensive and, thus, patients' selection for testing should be performed precisely. In 2012, an easy-to-use tool was developed in Exeter, UK, to support genetic testing for MODY in the British population. The aim of the study was to assess the utility of MODY Probability Calculator in probands from Polish families with early-onset autosomal dominant diabetes. METHODS: We have performed a retrospective analysis of 155 probands who were qualified for genetic testing between 2006 and 2018. Probands were recruited for MODY testing based on the following criteria: 1) early age of diagnosis (≤35 years); 2) a positive, multigenerational family history of diabetes. Automatic sequencing, Sanger and, in case of initial negative results, new generation sequencing (NGS) of a set of 28 genes, were performed. MODY Probability was calculated on the website www.diabetesgenes.org. RESULTS: The group of probands consisted of 64 GCK-, 37 HNF1A-, and three HNF4A-MODY patients and 51 NGS-negative subjects. The median positive predictive value (PPV) was 75.5% (95% CI: 75.5-75.5%), 49.4% (95% CI: 24.4-75.5%), 45.5% (95% CI: 21.0-75.5%) and 49.4% (95% CI: 32.9-75.5%) for GCK-, HNF1A-, HNF4A-MODY and NGS-negative, respectively. The discriminative accuracy, as expressed by AUC, of PPV between MODY and NGS negative groups was 0.62 (95% CI: 0.52-0.71) with the corresponding sensitivity of 71.2% and specificity of 51.0%. CONCLUSIONS: In this highly pre-selected group of probands that were qualified for genetic testing based on clinical features, the use of MODY Probability Calculator would not substantially improve the patients' selection process for genetic testing. Further efforts to improve this tool are desirable.