Introduction Totum-070 is a combination of five plant extracts enriched in polyphenols to target hypercholesterolemia, one of the main risk factors for cardiovascular diseases. The aim of this... Show moreIntroduction Totum-070 is a combination of five plant extracts enriched in polyphenols to target hypercholesterolemia, one of the main risk factors for cardiovascular diseases. The aim of this study was to investigate the effects of Totum-070 on cholesterol levels in an animal model of diet-induced hypercholesterolemia.Methods C57BL/6JOlaHsd male mice were fed a Western diet and received Totum-070, or not, by daily gavage (1g/kg and 3g/kg body weight) for 6 weeks.Results The Western diet induced obesity, fat accumulation, hepatic steatosis and increased plasma cholesterol compared with the control group. All these metabolic perturbations were alleviated by Totum-070 supplementation in a dose-dependent manner. Lipid excretion in feces was higher in mice supplemented with Totum-070, suggesting inhibition of intestinal lipid absorption. Totum-070 also increased the fecal concentration of short chain fatty acids, demonstrating a direct effect on intestinal microbiota.Discussion The characterization of fecal microbiota by 16S amplicon sequencing showed that Totum-070 supplementation modulated the dysbiosis associated with metabolic disorders. Specifically, Totum-070 increased the relative abundance of Muribaculum (a beneficial bacterium) and reduced that of Lactococcus (a genus positively correlated with increased plasma cholesterol level). Together, these findings indicate that the cholesterol-lowering effect of Totum-070 bioactive molecules could be mediated through multiple actions on the intestine and gut microbiota. Show less
Pieters, W.; Hugenholtz, F.; Kos, K.; Cammeraat, M.; Moliej, T.C.; Kaldenbach, D.; ... ; Riele, H. te 2022
The gut microbiota strongly impacts the development of sporadic colorectal cancer (CRC), but it is largely unknown how the microbiota affects the pathogenesis of mismatch-repair-deficient CRC in... Show moreThe gut microbiota strongly impacts the development of sporadic colorectal cancer (CRC), but it is largely unknown how the microbiota affects the pathogenesis of mismatch-repair-deficient CRC in the context of Lynch syndrome. In a mouse model for Lynch syndrome, we found a nearly complete loss of intestinal tumor development when animals were transferred from a conventional "open" animal facility to specific-pathogen-free (SPF) conditions. Using 16S sequencing we detected large changes in microbiota composition between the two facilities. Transcriptomic analyses of tumor-free intestinal tissues showed signs of strong intestinal inflammation in conventional mice. Whole exome sequencing of tumors developing in Msh2-Lynch mice revealed a much lower mutational load in the single SPF tumor than in tumors developing in conventional mice, suggesting reduced epithelial proliferation in SPF mice. Fecal microbiota transplantations with conventional feces altered the immune landscape and gut homeostasis, illustrated by increased gut length and elevated epithelial proliferation and migration. This was associated with drastic changes in microbiota composition, in particular increased relative abundances of different mucus-degrading taxa such as Desulfovibrio and Akkermansia, and increased bacterial-epithelial contact. Strikingly, transplantation of conventional microbiota increased microsatellite instability in untransformed intestinal epithelium of Msh2-Lynch mice, indicating that the composition of the microbiota influences the rate of mutagenesis in MSH2-deficient crypts. Show less
Background The gut fermentation syndrome (GFS), also known as the endogenous alcohol fermentation syndrome or auto brewery syndrome, is a rare and underdiagnosed medical condition where consumed... Show moreBackground The gut fermentation syndrome (GFS), also known as the endogenous alcohol fermentation syndrome or auto brewery syndrome, is a rare and underdiagnosed medical condition where consumed carbohydrates are converted to alcohol by the microbiota in the gastrointestinal or urinary tract. The symptoms of GFS can have severe impact on patients' wellbeing and can have social and legal consequences. Unfortunately, not much is reported about GFS. The aim of this systematic review was to assess the evidence for GFS, causal micro-organisms, diagnostics, and possible treatments.Methods A protocol was developed prior to initiation of the systematic review (PROSPERO 207182).We performed a literature search for clinical studies on 1 September 2020 using PubMed and Embase. We included all clinical studies, including case reports that described the GFS.Results In total, 17 case reports were included, consisting of 20 patients diagnosed with GFS. The species that caused the GFS included Klebsiella pneumoniae, Candida albicans, C. glabrata, Saccharomyces cerevisiae, C. intermedia, C. parapsilosis, and C. kefyr.Conclusions GFS is a rare but underdiagnosed disease in daily practice. The disease is mostly reported by Saccharomyces and Candida genera, and some cases were previously treated with antibiotics. Studies in Nonalcoholic Fatty Liver disease suggest a bacterial origin of endogenous alcohol-production, which might also be causal micro-organisms in GFS. Current treatments for GFS include antibiotics, antifungal medication, low carbohydrate diet, and probiotics. There might be a potential role of fecal microbiota transplant in the treatment of GFS. Show less
Background. Experimental murine models and human challenge studies of Salmonella Typhi infection have suggested that the gut microbiome plays an important protective role against the development of... Show moreBackground. Experimental murine models and human challenge studies of Salmonella Typhi infection have suggested that the gut microbiome plays an important protective role against the development of typhoid fever. Anaerobic bacterial communities have been hypothesized to mediate colonization resistance against Salmonella species by producing short-chain fatty acids, yet the composition and function of the intestinal microbiota in human patients with typhoid fever remain ill defined.Methods. We prospectively collected fecal samples from 60 febrile patients admitted to Chittagong Medical College Hospital, Bangladesh, with typhoid fever or nontyphoidal febrile illness and from 36 healthy age-matched controls. The collected fecal samples were subjected to 16s rRNA sequencing followed by targeted metabolomics analysis.Results. Patients with typhoid fever displayed compositional and functional disruption of the gut microbiota compared with patients with nontyphoidal febrile illness and healthy controls. Specifically, typhoid fever patients had lower microbiota richness and alpha diversity and a higher prevalence of potentially pathogenic bacterial taxa. In addition, a lower abundance of short-chain fatty acid-producing taxa was seen in typhoid fever patients. The differences between typhoid fever and nontyphoidal febrile illness could not be explained by a loss of colonization resistance after antibiotic treatment, as antibiotic exposure in both groups was similar.Conclusions. his first report on the composition and function of the gut microbiota in patients with typhoid fever suggests that the restoration of these intestinal commensal microorganisms could be targeted using adjunctive, preventive, or therapeutic strategies. Show less
When studying the microbiome using next-generation sequencing, the DNA extraction method, sequencing procedures, and bioinformatic processing are crucial to obtain reliable data. Method choice has... Show moreWhen studying the microbiome using next-generation sequencing, the DNA extraction method, sequencing procedures, and bioinformatic processing are crucial to obtain reliable data. Method choice has been demonstrated to strongly affect the final biological interpretation. We assessed the performance of three DNA extraction methods and two bioinformatic pipelines for bacterial microbiota profiling through 16S rRNA gene amplicon sequencing, using positive and negative controls for DNA extraction and sequencing and eight different types of high- or low-biomass samples. Performance was evaluated based on quality control passing, DNA yield, richness, diversity, and compositional profiles. All DNA extraction methods retrieved the theoretical relative bacterial abundance with a maximum 3-fold change, although differences were seen between methods, and library preparation and sequencing induced little variation. Bioinformatic pipelines showed different results for observed richness, but diversity and compositional profiles were comparable. DNA extraction methods were successful for feces and oral swabs, and variation induced by DNA extraction methods was lower than intersubject (biological) variation. For low-biomass samples, a mixture of genera present in negative controls and sample-specific genera, possibly representing biological signal, were observed. We conclude that the tested bioinformatic pipelines perform equally, with pipeline-specific advantages and disadvantages. Two out of three extraction methods performed equally well, while one method was less accurate regarding retrieval of compositional profiles. Lastly, we again demonstrate the importance of including negative controls when analyzing low-bacterial-biomass samples.IMPORTANCE Method choice throughout the workflow of a microbiome study, from sample collection to DNA extraction and sequencing procedures, can greatly affect results. This study evaluated three different DNA extraction methods and two bioinformatic pipelines by including positive and negative controls and various biological specimens. By identifying an optimal combination of DNA extraction method and bioinformatic pipeline use, we hope to contribute to increased methodological consistency in microbiota studies. Our methods were applied not only to commonly studied samples for microbiota analysis, e.g., feces, but also to more rarely studied, low-biomass samples. Microbiota composition profiles of low-biomass samples (e.g., urine and tumor biopsy specimens) were not always distinguishable from negative controls, or showed partial overlap, confirming the importance of including negative controls in microbiota studies, especially when low bacterial biomass is expected. Show less
Kurilshikov, A.; Munckhof, I.C.L. van den; Chen, L.M.; Bonder, M.J.; Schraa, K.; Rutten, J.H.W.; ... ; DEEP Cohort Study 2019
Intestinal failure (IF) is the reduction of gut function or mass below a minimum needed to absorb nutrients and fluids, such that patients are dependent on parenteral nutrition (PN). Patients with... Show moreIntestinal failure (IF) is the reduction of gut function or mass below a minimum needed to absorb nutrients and fluids, such that patients are dependent on parenteral nutrition (PN). Patients with IF have an altered gut microbiome. Our aim was to review and evaluate the current evidence on gut microbiome and its metabolic activity, as well as its association with disease characteristics in adults and children with IF. We performed a PubMed literature search for articles published after 2000 using the following terms: intestinal, microbiome, microbiota, short-chain fatty acids, short bowel syndrome, and PN. Literature search was restricted to human studies only. The gut microbiome diversity is remarkably reduced, and community structure is altered with a noticeable overabundance of Proteobacteria, especially the Enterobacteriaceae family. A substantial increase in Lactobacillus level is often reported in patients with IF. Gut microbiome characteristics have been associated with poor growth, liver disease, D-lactic acidosis, and duration of intestinal adaptation. Differences in microbiome characteristics have been found between patients receiving PN and those whose guts have adapted and have been weaned off PN. Future research with prospective sample collection should explore the value of the gut microbiome as a biomarker to guide clinical practice and as a modifiable therapeutic target to optimize outcomes of patients with IF. Show less
Does, A.M. van der; Amatngalim, G.D.; Keijser, B.; Hiemstra, P.S.; Villenave, R. 2018
Diets and food are indisputably core facets of human society. The great apes still rely on plants to supply most of their nutritional needs. Humans, however consume a diet that is nearly... Show moreDiets and food are indisputably core facets of human society. The great apes still rely on plants to supply most of their nutritional needs. Humans, however consume a diet that is nearly unrecognizable from that of early hominin and human ancestors. While the virtues of plant foods are widely extolled, it is done so without a regard for how wild and unrefined plant foods must have contributed to the diets of our pre-agricultural ancestors. The purpose of my dissertation was to examine how wild African tubers, which are targeted by the Hadza hunter-gatherers of Tanzania, contribute the nutritional elements that are essential for health and survival in the East African mosaic environment. To accomplish this objective, I conducted three projects. First, I tested the efficacy of brief roasting, used by the Hadza, on starch gelatinization. Second, I submitted four species of Hadza tubers to an in-vitro simulation of the gastro-intestinal tract, and measured the bioaccessibility of glucose from digestion. Finally, I led an analysis of the Hadza gut microbiome to explore the polysaccharide degrading potential of mutualistic microbiota and learn whether Hadza may be better provisioned by metabolites from fermentation of the residual indigestible plant fibers in their diet. Show less
