Microbiota Of Subjects Research Articles

Effects of Sucralose Supplementation on Glycemic Response, Appetite, and Gut Microbiota in Subjects with Overweight or Obesity: A Randomized Crossover Study Protocol.

Sucralose stands as the most common non-nutritive sweetener; however, its metabolic effects have sparked significant controversy over the years. We aim to examine the effects of sucralose daily intake on glycemia, subjective appetite, and gut microbiota (GM) changes in subjects with overweight or obesity. In this randomized, crossover, and controlled trial, 23 participants with a body mass index between 25 kg/m2 and 39.9 kg/m2 will be assigned to one of two interventions to receive either sucralose (2 mg/kg/day equivalent to 40% of the acceptable daily intake) or glucose (control) for 4 weeks, each phase separated by a 4-week washout period. The glycemic response will be determined during a meal tolerance test, subjective appetite will be evaluated using a visual analog scale, and GM changes will be analyzed by next-generation sequencing of the bacterial rRNA 16S gene from fecal samples. All measures will be performed before and after intervention periods. We hypothesize that sucralose supplementation induces changes in glycemic response, subjective appetite, and gut microbiota in overweight and obese participants. This protocol was approved by the Ethics Committee of the UJAT (No. 0721) and was registered in the Australian New Zealand Clinical Trials Registry (ACTRN12621001531808).

Effect of Lacticaseibacillus casei LC2W Supplementation on Glucose Metabolism and Gut Microbiota in Subjects at High Risk of Metabolic Syndrome: A Randomized, Double-blinded, Placebo-controlled Clinical Trial.

Metabolic syndrome (MetS) is a global epidemic complex and will cause serious metabolic comorbidities without treatment. A prevention strategy for MetS development has been proposed to modulate gut microbiota by probiotic administrationto improve intestinal dysbiosis and benefit the host. Lacticaseibacillus casei LC2W has exhibited positive effects in preventing colitis and anti-hypertension in vivo. However, the effect of L. casei LC2W on subjects at high risk of MetS is unknown. Here, a randomized, double-blinded, placebo-controlled study was conducted on 60 subjects with high risk of MetS, and the hypoglycemic and hypolipidemic activity and possible pathways of L. casei LC2W were inferred from the correlation analysis with gut microbiome composition, function, and clinical phenotypic indicators. The results showed that oral administration of L. casei LC2W could exert significant benefits on weight control, glucose and lipid metabolism, inflammatory and oxidative stress parameters, and SCFA production, as well as modulate the composition of gut microbiota. The relative abundance of Lacticaseibacillus, Bifidobacterium, Dorea, and Blautia was enriched, and their interaction with other gut microbes was strengthened by oral administration of L. casei LC2W, which was beneficial in ameliorating gut inflammation, promoting glucose and lipids degradation pathways, thus alleviated MetS. The present study confirmed the prevention effects of L. casei LC2W towards MetS from aspects of clinical outcomes and microflora modulation, providing an alternative strategy for people at high risk of MetS.Trial registration: The study was proactively registered in ClinicalTrial.gov with the registration number of ChiCTR2000031833 on April 09, 2020.

A Probiotic Amylase Blend Positively Impacts Gut Microbiota Modulation in a Randomized, Placebo-Controlled, Double-Blind Study.

The present study was performed to determine if ingesting a blend of probiotics plus amylase would alter the abundance and diversity of gut microbiota in subjects consuming the blend over a 6-week period. 16S and ITS ribosomal RNA (rRNA) sequencing was performed on fecal samples provided by subjects who participated in a clinical study where they consumed either a probiotic amylase blend (Bifidobacterium breve 19bx, Lactobacillus acidophilus 16axg, Lacticaseibacillus rhamnosus 18fx, and Saccharomyces boulardii 16mxg, alpha amylase (500 SKB (Alpha-amylase-Dextrinizing Units)) or a placebo consisting of rice oligodextrin. The abundance and diversity of both bacterial and fungal organisms was assessed at baseline and following 6 weeks of probiotic amylase blend or placebo consumption. In the subjects consuming the probiotic blend, the abundance of Saccharomyces cerevisiae increased 200-fold, and its prevalence increased (~20% to ~60%) (p ≤ 0.05), whereas the potential pathogens Bacillus thuringiensis and Macrococcus caseolyticus decreased more than 150- and 175-fold, respectively, after probiotic-amylase blend consumption. We also evaluated the correlation between change in microbiota and clinical features reported following probiotic amylase consumption. Nine (9) species (seven bacterial and two fungal) were significantly (negatively or positively) associated with the change in 32 clinical features that were originally evaluated in the clinical study. Oral supplementation with the probiotic-amylase blend caused a marked increase in abundance of the beneficial yeast S. cerevisiae and concomitant modulation of gut-dwelling commensal bacterial organisms, providing the proof of concept that a beneficial commensal organism can re-align the gut microbiota.

Influence of obesity on subgingival microbiota composition in subjects with different periodontal status: a systematic review.

This systematic review aimed to investigate the changes in the composition of the subgingival microbiota among subjects with normo-weight, overweight and obesity, in conditions of periodontal health and disease. The protocol for this study was designed following PRISMA guidelines. Records were identified using different search engines (PubMed/MedLine, Scopus and Web of Science). Observational studies, in human subjects diagnosed with obesity (BMI >30kg/m2) and periodontal disease (gingivitis and periodontitis), on the analysis of subgingival microbiota were selected. Eight articles were included. The subgingival microbiota of 1,229 subjects (n=894 exposure group and n=335 control group) was analyzed. Periodontal pathogens were the most common bacteria detected in subjects with obesity and periodontitis (Porphyromonas gingivalis, Tannerella forsythia, Campylobacter gracilis, Eubacterium nodatum, Fusobacterium nucleatum spp. vincentii, Parvimonas micra, Prevotella intermedia, Campylobacter rectus, and Aggregatibacter actinomycetemcomitans), as along with some accessory pathogens such as: Streptococcus gordonii, and Veillonella parvula that favor the virulence of late colonizers. Although there are evident alterations in the composition of the subgingival microbiota in subjects with obesity and periodontitis, it is still a challenge to identify a specific pattern of microbiota in these subjects. If associations between subgingival plaque microorganisms and obesity are confirmed, microbiome analysis could be a useful tool to improve preventive measures and the management of people with obesity.

Alterations of ileal mucosa-associated microbiota in hypercholesterolemia patients

Many metabolic diseases have been demonstrated to be associated with changes in the microbiome. However, no studies have yet been conducted to examine the characteristics of the mucosal microbiota of patients with hypercholesterolemia. We aimed to examine mucosa-associated microbiota in subjects with hypercholesterolemia. We conducted a case-control study, in which ileal mucosal samples were collected from 13 hypercholesterolemia patients and 13 controls for 16S rRNA gene sequencing. There were differences in the composition of ileal mucosal microbiota based on beta diversity between the hypercholesterolemia and control groups (P < 0.05). Compared with the control group, the phylum Bacteroidetes and the genera Bacteroides, Butyricicoccus, Parasutterella, Candidatus_Soleaferrea, and norank_f__norank_o__Izemoplasmatales were less abundant in the hypercholesterolemia group (P < 0.05), while the genus Anaerovibrio was enriched in the hypercholesterolemia group (P < 0.05). The relative abundance of Bacteroides was negatively correlated with total cholesterol and low-density lipoprotein cholesterol (P < 0.01). The relative abundance of Coprococcus was negatively correlated with triglycerides and body mass index (all P < 0.05). PICRUSt functional prediction analysis showed that pathways related to Glycerophospholipid metabolism, ABC transporters, Phosphotransferase system, and Biofilm formation - Escherichia coli, and infectious diseases of pathogenic Escherichia coli were enriched in the hypercholesterolemia group. This work suggests a potential role of ileal mucosal microbiota in the development of hypercholesterolemia.

Clostridioides difficile and Enterococci's Interplay in the Human Gut: Bacterial Alliance or Competition? A Systematic Literature Review.

Clostridioides difficile and Enterococcus spp. are two common bacterial pathogens populating the human microbiota. We possess scant data on how Clostridioides difficile interacts with Enterococcus spp. in the gut microbiota in subjects colonized with Clostridioides difficile or during a Clostridioides difficile infection. We carried out a systematic review of studies on Enterococcus spp. and Clostridioides difficile's interaction in the gut microbiota and on the effect of Enterococcus spp. gut colonization on CDI development. Studies on Enterococcus spp. and Clostridioides difficile's interaction in the gut microbiota and on the effect of Enterococcus spp. gut colonization on CDI were searched using the search terms "clostridium", "clostridioides", "difficile" and "enterococcus" on the MEDLINE and SCOPUS databases. PubMed was searched until 1 May 2023. An English language restriction was applied. The risk of bias in the included studies was not assessed. Quantitative and qualitative information was summarized in textual descriptions. Fourteen studies, published from August 2012 to November 2022, on Clostridioides difficile and Enterococcus spp.'s interaction in the gut microbiota met the inclusion criteria. The studies included in our systematic review reported evidence that the Enterococcus spp. intestinal burden represents a risk factor for the occurrence of CDI. There is supporting evidence that Enterococcus spp. play a role in CDI development and clinical outcomes.

The role of gut microbiota in the development of obesity in dogs

The gut microbiota has become the subject of extensive research in the last decades. Intensive research has revealed its role in several functions related to energy metabolism as well as its importance in both health and illness. An imbalance in gut microbiota composition results in dysbiosis, which has been associated with metabolic disorders such as obesity. In the latter context, the gut microbiota appears to mediate the impact of diet on the host body weight. There are many studies in rodents that show profound changes in the composition and metabolic function of the gut microbiota in subjects with obesity, indicating its influence on the development of the problem. Usually, the microbiota of obese dogs has a modified Firmicutes:Bacteroidetes ratio, which returns to normal values after dietary intervention with diet-induced weight loss. The role of the gut microbiota on the development of dog obesity is a recent topic of research, which has been complex due to most of the studies being carried out using commercial extruded diets, which differ in their nutritional composition, resulting in controversial findings. Nevertheless, it has been shown that macro-nutrients from the diet are the most relevant factors that can modulate the microbiota’s composition in a particular way. Moreover, current studies indicate that a personalized nutritional intervention could modify the composition and function of gut microbiota in a positive manner, reducing the development of pathologies such as obesity.

Changes of gut microbiota in patients at different phases of stroke.

Gut dysbiosis appears rapidly after acute stroke and may affect the prognosis, whereas changes in gut microbiota with gradual recovery from stroke are unknown and rarely studied. The purpose of this study is to explore the characteristics of gut microbiota changes over time after stroke. Stroke patients and healthy subjects were selected to compare the clinical data and gut microbiota of the patient group in two phases with that of healthy subjects and 16S rRNA gene sequencing was used to search the differences of gut microbiota in subjects. Compared with the healthy subjects, the subacute patients mainly decreased the abundance of some gut microbial communities, while the decreased communities reduced and more communities increased the abundance in the convalescent patients. The abundance of Lactobacillaceae increased in both phases in patient group, while Butyricimona, Peptostreptococaceae and Romboutsia decreased in both phases. Correlation analysis found that the MMSE scores of patients in the two phases had the greatest correlation with the gut microbiota. Gut dysbiosis still existed in patients in the subacute phase and convalescent phase, and gradually improved with the recovery of stroke. Gut microbiota may affect the prognosis of stroke by affecting BMI and/or related indicators, and there is a strong correlation between gut microbiota and cognitive function after stroke.

Effects of Animal and Vegetable Proteins on Gut Microbiota in Subjects with Overweight or Obesity.

The gut microbiota plays a pivotal role in the balance between host health and obesity. The composition of the gut microbiota can be influenced by external factors, among which diet plays a key role. As the source of dietary protein is important to achieve weight loss and gut microbiota modulation, in the literature there is increasing evidence to suggest consuming more plant proteins than animal proteins. In this review, a literature search of clinical trials published until February 2023 was conducted to examine the effect of different macronutrients and dietary patterns on the gut microbiota in subjects with overweight and obesity. Several studies have shown that a higher intake of animal protein, as well as the Western diet, can lead to a decrease in beneficial gut bacteria and an increase in harmful ones typical of obesity. On the other hand, diets rich in plant proteins, such as the Mediterranean diet, lead to a significant increase in anti-inflammatory butyrate-producing bacteria, bacterial diversity and a reduction in pro-inflammatory bacteria. Therefore, since diets rich in fiber, plant protein, and an adequate amount of unsaturated fat may help to beneficially modulate the gut microbiota involved in weight loss, further studies are needed.

Influence of Butyrate on Impaired Gene Expression in Colon from Patients with High Blood Pressure.

Hypertension (HTN) is associated with gut dysbiosis and the depletion of butyrate-producing bacteria in animal models and people. Furthermore, fecal material transfer from donor hypertensive patients increases blood pressure in normotensive recipient animals and ameliorates HTN-associated pathophysiology. These observations have implications in the impaired interactions between the gut and gut microbiota in HTN. Although this concept is supported in animal models, little is known about human HTN. Therefore, our objective for this study was to compare gene expression with transcriptomics and its potential to influence microbiota in subjects with normal and high blood pressure (HBP). Colon samples from reference subjects with normal blood pressure (REF) and HBP were used for RNA-seq to analyze their transcriptomes. We observed the significant downregulation of gene sets governing immune responses (e.g., SGK1 and OASL), gut epithelial function (e.g., KRT20 and SLC9A3R1), gut microbiota (e.g., PPARG and CIDEC) and genes associated with cardiovascular and gut diseases (e.g., PLAUR and NLN) in HBP subjects; the expression of genes within these pathways correlated with blood pressure. Potential drug targets in the gut epithelium were identified using the Drug Gene International Database for possible use in HTN. They include peroxisome proliferator-activated receptor gamma (PPRG), active serum/glucocorticoid regulated kinase 1 (SGK1) and 3 beta-hydroxysteroid isomerase type II inhibitor (HSD3B). Finally, butyrate, a microbiota-derived short-chain fatty acid, restored the disrupted expression of certain functional genes in colonic organoids from HBP subjects. Patients with HBP exhibit a unique transcriptome that could underlie impaired gut-microbiota interactions. Targeting these interactions could provide a promising new therapeutic intervention for hypertension management.

The intestinal microbiota as an ally in the treatment of Alzheimer's disease.

The evolution of the understanding of the intestinal microbiota and its influence on our organism leverages it as a potential protagonist in therapies aimed at diseases that affect not only the intestine but also neural pathways and the central nervous system itself. This study, developed from a thorough systematic review, sought to demonstrate the influence of the intervention on the intestinal microbiota in subjects with Alzheimer's disease. Clinical trials using different classes of probiotics have depicted noteworthy remission of symptoms, whose measurement was performed based on screenings and scores applied before, during, and after the period of probiotics use, allowing the observation of changes in functionality and symptomatology of patients. On the other hand, faecal microbiota transplantation requires further validation through clinical trials, even though it has already been reported in case studies as promising from the symptomatology point of view. The current compilation of studies made it possible to demonstrate the potential influence of the intestinal microbiota on Alzheimer's pathology. However, new clinical studies with a larger number of participants are needed to obtain further clarification on pathophysiological correlations.

Gut microbiota modulates differential lipid metabolism outcomes associated with FTO gene polymorphisms in response to personalized nutrition intervention.

BackgroundInterindividual differences in response to personalized nutrition (PN) intervention were affected by multiple factors, including genetic backgrounds and gut microbiota. The fat mass and obesity associated (FTO) gene is an important factor related to hyperlipidemia and occurrence of cardiovascular diseases. However, few studies have explored the differences in response to intervention among subjects with different genotypes of FTO, and the associations between gut microbiota and individual responses.ObjectiveTo explore the differential lipid metabolism outcomes associated with FTO gene polymorphisms in response to PN intervention, the altered taxonomic features of gut microbiota caused by the intervention, and the associations between gut microbiota and lipid metabolism outcomes.MethodsA total of 400 overweight or obese adults were recruited in the study and randomly divided into the PN group and control group, of whom 318 completed the 12-week intervention. The single nucleotide polymorphism (SNP) of rs1121980 in FTO was genotyped. Gut microbiota and blood lipids were determined at baseline and week 12. Functional property of microbiota was predicted using Tax4Fun functional prediction analysis.ResultsSubjects with the risk genotype of FTO had significantly higher weight and waist circumference (WC) at baseline. Generalized linear regression models showed that the reduction in weight, body mass index (BMI), WC, body fat percentage, total cholesterol (TCHO), and low-density lipoprotein (LDL) was greater in subjects with the risk genotype of FTO and in the PN group. Significant interaction effects between genotype and intervention on weight, BMI, WC, TCHO, and LDL were found after stratifying for specific genotype of FTO. All subjects showed significant increasement in α diversity of gut microbiota after intervention except for those with the non-risk genotype in the control group. Gut microbiota, including Blautia and Firmicutes, might be involved in lipid metabolism in response to interventions. The predicted functions of the microbiota in subjects with different genotypes were related to lipid metabolism-related pathways, including fatty acid biosynthesis and degradation.ConclusionSubjects with the risk genotype of FTO had better response to nutrition intervention, and PN intervention showed better amelioration in anthropometric parameters and blood lipids than the control. Gut microbiota might be involved in modulating differential lipid metabolism responses to intervention in subjects with different genotypes.Trial registration[Chictr.org.cn], identifier [ChiCTR1900026226].

Chitin-glucan supplementation improved postprandial metabolism and altered gut microbiota in subjects at cardiometabolic risk in a randomized trial

Chitin-glucan (CG), an insoluble dietary fiber, has been shown to improve cardiometabolic disorders associated with obesity in mice. Its effects in healthy subjects has recently been studied, revealing its interaction with the gut microbiota. In this double-blind, randomized, cross-over, twice 3-week exploratory study, we investigated the impacts of CG on the cardiometabolic profile and gut microbiota composition and functions in 15 subjects at cardiometabolic risk. They consumed as a supplement 4.5 g of CG daily or maltodextrin as control. Before and after interventions, fasting and postprandial metabolic parameters and exhaled gases (hydrogen [H2] and methane [CH4]) were evaluated. Gut microbiota composition (16S rRNA gene sequencing analysis), fecal concentrations of bile acids, long- and short-chain fatty acids (LCFA, SCFA), zonulin, calprotectin and lipopolysaccharide binding protein (LBP) were analyzed. Compared to control, CG supplementation increased exhaled H2 following an enriched-fiber breakfast ingestion and decreased postprandial glycemia and triglyceridemia response to a standardized test meal challenge served at lunch. Of note, the decrease in postprandial glycemia was only observed in subjects with higher exhaled H2, assessed upon lactulose breath test performed at inclusion. CG decreased a family belonging to Actinobacteria phylum and increased 3 bacterial taxa: Erysipelotrichaceae UCG.003, Ruminococcaceae UCG.005 and Eubacterium ventriosum group. Fecal metabolites, inflammatory and intestinal permeability markers did not differ between groups. In conclusion, we showed that CG supplementation modified the gut microbiota composition and improved postprandial glycemic response, an early determinant of cardiometabolic risk. Our results also suggest breath H2 production as a non-invasive parameter of interest for predicting the effectiveness of dietary fiber intervention.

IDF21-0087 Metabolic interventions for diabetes treatment are associated with gut microbiota changes: a systematic review

Background: Increasing loss of gut microbial diversity has been implicated in diabetes and prediabetes. Recent studies assessed the changes on microbiome composition due to interventions for diabetes treatment. Aim: This systematic review aimed to assess if dietary, surgical and pharmacological interventions can change gut microbiota in subjects with diabetes. Method: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Statement was followed for conducting and reporting this systematic review. A vote-counting method to assess the effect of interventions on relevant outcomes was applied. Inclusion criteria were: adults with type 1 or 2 diabetes diagnosis and focus on gut microbiota, which involved any intervention or combination of glycemic control interventions. The terms “diabetes mellitus” and “microbiota” were used in the selected databases in the article search. The studies were grouped by intervention type (dietary, surgical and pharmacological) and then classified based on their impact in the α-diversity and in individual bacterial abundances following the intervention. Results: The electronic search returned 5807 potentially relevant studies; after removing duplicates, 5218 studies were retained for review of titles and abstracts. The 130 full-text articles retained were reassessed, 37 of which were included. Dietary interventions that increased Lactobacillus genus include high consumption of lactic acid bacteria and oligosaccharides; an increase of Faecalibacterium was found in four studies. Concerning bariatric surgery, nine small studies with controversial results were examined. Among microbial species affected by the procedure, Veillonella was increased in seven studies, whereas the increase of genus Akkermansia was found only in one study. Nevertheless, the species Akkermansia muciniphila was increased in all types of interventions. Considering the pharmacological interventions, microbial α-diversity was reported in seven studies using different indices and methods, and studies indicated a significant difference in this index after the intervention with acarbose, metformin and metformin plus traditional Chinese medicine. The study with metformin reported an increase of Mobilitalea, Lactobacillus, Akkermansia and a decrease of Oscilibacter, Alloprevotella and Bifidobacterium. Discussion: Clinical heterogeneity precluded performing a meta-analysis. Analyzing the effects of interventions on gut microbial composition remains a challenge due to a multitude of factors. Overall, all three interventions increased more gram-positive bacteria from the Phylum Firmicutes than gram-negative bacteria from the Phylum Bacteroidetes. This balance may be suitable in patients with diabetes, once lipopolysaccharides produced by gram-negative bacterial cell may stimulate systemic inflammation, increasing insulin resistance. These results suggest that the interventions addressed to a reduction of species related to uncontrolled diabetes and to an increase of species related to a healthy gut.

Gut Bifidobacterium responses to probiotic Lactobacillus casei Zhang administration vary between subjects from different geographic regions.

Bifidobacteria are health-promoting human gut inhabitants, but accurate species-level composition of the gut bifidobacteria and their responses to probiotic intervention have not been fully explored. This was a follow-up work of our previous study, in which 104 volunteers from six different Asiatic regions (Singapore, Indonesia, Xinjiang, Gansu, Inner Mongolia, Mongolia) were recruited. The gut microbiota and their responses towards Lactobacillus casei Zhang (LCZ) intervention were characterized (at days 0, 7, and 14; 14days after stopping probiotic intake), and region-based differential responses were observed after LCZ intervention. This study further investigated changes in the species-level gut bifidobacteria by PacBio small-molecule real-time sequencing (SMRT) using bifidobacteria-specific primers. Firstly, this study found that Bifidobacterium adolescentis (42.58%) and Bifidobacterium breve (26.34%) were the core species across the six Asiatic regions. Secondly, principal coordinate analysis of probiotic-induced changes in the gut bifidobacterial microbiota (represented by weighted UniFrac distances) grouped the six regions into two clusters, namely northern (Xinjiang, Gansu, Inner Mongolia, and Mongolia) and southern (Singapore, Indonesia) regions. Thirdly, LCZ intervention induced region-based differential responses of gut bifidobacterial microbiota. The relative abundance of Bifidobacterium animalis in subjects from northern but not southern region substantially increased after LCZ intervention. Moreover, LCZ intervention significantly increased the weighted UniFrac distances in the southern but not northern subjects 7days after LCZ intervention. The gut B. adolescentis correlated significantly and negatively with the weighted UniFrac distances of the baseline gut bifidobacterial microbiota in subjects of northern but not southern region, suggesting a possible homeostatic effect of LCZ on the gut bifidobacterial population of northern but not southern subjects. Collectively, our study found that probiotic-induced responses of the gut bifidobacterial microbiota varied with subjects' geographic origins, and B. adolescentis might play a role in maintaining the overall stability of the gut bifidobacterial population. KEY POINTS: • The core species in the six Asiatic regions are Bifidobacterium adolescentis and Bifidobacterium breve. • The gut bifidobacterial microbiota in people from various geographic origins showed different responses on probiotic administration.

Protocol Standardization of Microbiome Studies—Daunting but Necessary

Protocol Standardization of Microbiome Studies—Daunting but Necessary

Fecal microbiota transplantation ameliorates atherosclerosis in mice with C1q/TNF-related protein 9 genetic deficiency

Despite the strong influence of the gut microbiota on atherosclerosis, a causal relationship between atherosclerosis pathophysiology and gut microbiota is still unverified. This study was performed to determine the impact of the gut microbiota on the pathogenesis of atherosclerosis caused by genetic deficiency. To elucidate the influence of the gut microbiota on atherosclerosis pathogenesis, an atherosclerosis-prone mouse model (C1q/TNF-related protein 9-knockout (CTRP9-KO) mice) was generated. The gut microbial compositions of CTRP9-KO and WT control mice were compared. Fecal microbiota transplantation (FMT) was performed to confirm the association between gut microbial composition and the progression of atherosclerosis. FMT largely affected the gut microbiota in both CTRP9-KO and WT mice, and all transplanted mice acquired the gut microbiotas of the donor mice. Atherosclerotic lesions in the carotid arteries were decreased in transplanted CTRP9-KO mice compared to CTRP9-KO mice prior to transplantation. Conversely, WT mice transplanted with the gut microbiotas of CTRP9-KO mice showed the opposite effect as that of CTRP9-KO mice transplanted with the gut microbiotas of WT mice. Here, we show that CTRP9 gene deficiency is related to the distribution of the gut microbiota in subjects with atherosclerosis. Transplantation of WT microbiotas into CTRP9-KO mice protected against the progression of atherosclerosis. Conversely, the transplantation of CTRP9-KO microbiotas into WT mice promoted the progression of atherosclerosis. Treating atherosclerosis by restoring gut microbial homeostasis may be an effective therapeutic strategy.

Gut microbiota of patients with type 2 diabetes and gastrointestinal intolerance to metformin differs in composition and functionality from tolerant patients.

Metformin modifies the gut microbiome in type 2 diabetes and gastrointestinal tolerance to metformin could be mediated by the gut microbiome. We enrolled 35 patients with type 2 diabetes not receiving treatment with metformin due to suspected gastrointestinal intolerance. Metformin was reintroduced at 425mg, increasing 425mg every two weeks until reaching 1700mg per day. According to the occurrence of metformin-related gastrointestinal symptoms, patients were classified into three groups: early intolerance, non-tolerant, and tolerant. Gut microbiota was profiled with 16S rRNA. This sequencing aimed to determine the differences in the baseline gut microbiota in all groups and prospectively in the tolerant and non-tolerant groups. The classification resulted in 15 early intolerant, 10 tolerant, and 10 non-tolerant subjects. Early tolerance was characterized by a higher abundance of Subdoligranulum; while Veillonella and Serratia were higher in the non-tolerant group. The tolerant group showed enrichment of Megamonas, Megamonas rupellensis, and Phascolarctobacterium spp; Ruminococcus gnavus was lower in the longitudinal analysis. At the end point Prevotellaceae, Prevotella stercorea, Megamonas funiformis, Bacteroides xylanisolvens, and Blautia producta had a higher relative abundance in the tolerant group compared to the non-tolerant group. Subdoligranulum, Ruminococcus torques_1, Phascolarctobacterium faecium, and Eubacterium were higher in the non-tolerant group. The PICRUSt analysis showed a lower activity of the amino acid biosynthesis pathways and a higher sugar degradation pathway in the intolerant groups. Gut microbiota of subjects with gastrointestinal intolerance depicted taxonomic and functional differences compared to tolerant patients, and this changed differently after metformin administration.

Characterization of the blood microbiota in children with Celiac disease.

Celiac Disease (CD) is an autoimmune disorder triggered by gluten ingestion that can develop in genetically predisposed individuals. Alterations in the gut microbiota have been suggested to contribute to development of autoimmune conditions including CD. Recent work suggests the existence of a blood microbiota. Evidence that alterations in the blood microbiota potentially influence the development of chronic immune based diseases is increasing. However, there is no published literature regarding the blood microbiota in children, including those with CD. This study aimed to characterize the diversity and taxonomic composition of the blood microbiota of children with CD compared to controls. Whole blood samples were collected from children with active CD, CD in remission, and control subjects and 16S rRNA sequencing was utilized to analyze the blood microbiota. We found 16s rRNA present throughout all pediatric blood samples, providing evidence for the presence of a pediatric blood microbiota. We found significant differences in beta diversity and in abundance of certain taxa (Campylobacterales order, Odoribacteraceae and Helicobacteraceae families, Odoribacter genus and species, and Bacteroides acidifaciens species) between subjects with active CD and controls. These taxa have been previously reported to be associated with immune response and gut-inflammatory diseases. We did not find significant differences between subjects with active and remission CD or between remission CD and controls. Conclusions: We provide evidence for a pediatric blood microbiota and identified higher beta diversity and alterations in the composition of blood microbiota in subjects with active CD compared to controls.

Oral Microbiota and Salivary Levels of Oral Pathogens in Gastro-Intestinal Diseases: Current Knowledge and Exploratory Study.

Various bi-directional associations exist between oral health and gastro-intestinal diseases. The oral microbiome plays a role in the gastro-intestinal carcinogenesis and fusobacteria are the most investigated bacteria involved. This paper aims to review the current knowledge and report the preliminary data on salivary levels of Fusobacterium nucleatum, Porphyromonas gingivalis and Candida albicans in subjects with different gastro-intestinal conditions or pathologies, in order to determine any differences. The null hypothesis was “subjects with different gastro-intestinal diseases do not show significant differences in the composition of the oral microbiota”. Twenty-one subjects undergoing esophagastroduodenoscopy or colonscopy were recruited. For each subject, a salivary sample was collected before the endoscopy procedure, immediately stored at −20 °C and subsequently used for genomic bacterial DNA extraction by real-time PCR. Low levels of F. nucleatum and P. gingivalis were peculiar in the oral microbiota in subjects affected by Helicobater pylori-negative chronic gastritis without cancerization and future studies will elucidate this association. The level of C. albicans did not statistically differ among groups. This preliminary study could be used in the future, following further investigation, as a non-invasive method for the search of gastrointestinal diseases and associated markers.