Biology subjects

Mentzel, C. M. J.

Publications and source records attributed to Mentzel, C. M. J..

4 recordsLinked to original sources

bioRxiv2023

Investigating the Rescue Potential of Fecal Microbiota Transplants in Anorexia Nervosa using Antibiotic-treated Mice in a Split Group Cross-Over Study

Anorexia nervosa (AN) is a complex and serious mental disorder, which may affect individuals of all ages and sex, but primarily affecting young women. The disease is characterized by a disturbed body image, restrictive eating behavior, and a lack of acknowledgment of low body weight. The underlying causes of AN remain largely unknown, and current treatment options are limited to psychotherapy and nutritional support. This paper investigates the impact of Fecal Microbiota Transplants (FMT) from AN patients on food intake, body weight, behavior, and gut microbiota in antibiotic-treated mice. Two rounds of FMT were performed using AN and control (CO) donors. During the second round of FMT, a subset of mice received FMT from a different donor type. This split-group cross-over design was chosen to demonstrate any recovery effect of FMT from a healthy donor. The first FMT, from AN donors, resulted in lower food intake in mice without affecting body weight. After FMT2, serum analysis revealed higher levels of appetite-influencing hormones (PYY and leptin) in mice receiving AN-GM. Gut microbiota analysis showed significant differences between AN and CO mice after FMT1, before cross-over. Specific bacterial genera and families Ruminococcaceae, Lachnospiraceae, and Faecalibacterium showed different abundances in AN and CO receiving mice. Behavioral tests showed decreased locomotor activity in AN mice after FMT1. Overall, the results suggest that AN-GM may contribute to altered food intake and appetite regulation, which can be ameliorated with FMT from a healthy donor potentially offering FMT as a supportive treatment for AN.

microbiology↗

bioRxiv2022

Dietary non-starch polysaccharides impair immunity to enteric nematode infection

The influence of diet on immune function and resistance to enteric infection and disease is becoming ever more established. Highly processed, refined diets can lead to inflammation and gut microbiome dysbiosis, whilst health-promoting dietary components such as phytonutrients and fermentable fibres are thought to promote a healthy microbiome and balanced mucosal immunity. Chicory (Cichorium intybus) is a leafy green vegetable rich in fibres and bioactive compounds that may promote gut health. Unexpectedly, we here show that incorporation of chicory into semisynthetic AIN93G diets renders mice susceptible to infection with enteric helminths. Mice fed a high level of chicory leaves (10% dry matter) had a more diverse gut microbiota, but a diminished type-2 immune response to infection with the intestinal roundworm Heligmosomoides polygyrus. Furthermore, the chicory-supplemented diet significantly increased burdens of the caecum-dwelling whipworm Trichuris muris, concomitant with a highly skewed type-1 immune environment in caecal tissue. The chicory-supplemented diet was rich in non-starch polysaccharides, particularly uronic acids (the monomeric constituents of pectin). In accordance, mice fed pectin-supplemented AIN93G diets had higher T. muris burdens and reduced IgE production and expression of genes involved in type-2 immunity. Importantly, treatment of pectin-fed mice with exogenous IL-25 restored type-2 responses and was sufficient to allow T. muris expulsion. Collectively, our data suggest that increasing levels of fermentable, non-starch polysaccharides in refined diets compromises immunity to helminth infection in mice. This diet-infection interaction may inform new strategies for manipulating the gut environment to promote resistance to enteric parasites.

immunology↗

bioRxiv2022

Fecal virome transfer improves proliferation of commensal gut Akkermansia muciniphila and unexpectedly enhances the fertility rate in laboratory mice

Probiotics have been suggested as nutritional supplements to improve gastrointestinal health. However, the probiotics marketed today only colonize the densely populated gut to a limited extent. Bacteriophages comprise the majority of viruses in the human gut virome and there are strong indications that they play important roles in shaping the gut microbiome (GM). Here we investigate the use of fecal virome transplantation (FVT) as a mean to alter GM composition to lead the way for persistent colonization of two types of probiotics: Lacticaseibacillus rhamnosus GG (LGG) representing a well-established probiotic and Akkermansia muciniphila (AKM) representing a putative next-generation probiotic. Male and female C57BL/6NTac mice were cohoused in pairs at 4 weeks of age and received the following treatment by oral gavage at week 5 and 6: AKM+FVT, probiotic sham (Pro-sham)+FVT, LGG+Saline, AKM+Saline, and control (Pro-sham+Saline). The FVT originated from donor mice with high relative abundance of A. muciniphila. All animals were terminated at age 9 weeks. The FVT treatment did not increase the relative abundance of the administered LGG or AKM in the recipient mice. Instead FVT significantly (p<0.05) increased the abundance of naturally occurring A. muciniphila compared to the control. This highlights the potential of stimulating the commensal "probiotics" that already are permanent members of the gut. Being co-housed male and female, a fraction of the female mice became pregnant. Unexpectedly, the FVT treated mice were found to have a significantly (p<0.05) higher fertility rate independent of probiotic administration. These preliminary observations urge for follow-up studies investigating GM/fertility interactions.

microbiology↗

bioRxiv2019

Faecal virome transplantation decrease symptoms of type-2-diabetes and obesity in a murine model

ObjectiveDevelopment of obesity and type-2-diabetes (T2D) are associated with gut microbiota (GM) changes. The gut viral community is predominated by bacteriophages (phages), which are viruses that attack bacteria in a host-specific manner. As a proof-of-concept we demonstrate the efficacy of faecal virome transplantation (FVT) from lean donors for shifting the phenotype of obese mice into closer resemblance of lean mice.\n\nDesignThe FVT consisted of viromes extracted from the caecal content of mice fed a low-fat (LF) diet for fourteen weeks. Male C57BL/6NTac mice were divided into five groups: LF (as control), high-fat diet (HF), HF+Ampicillin (Amp), HF+Amp+FVT and HF+FVT. At week six and seven of the study the HF+FVT and HF+Amp+FVT mice were treated with FVT by oral gavage. The Amp groups were treated with ampicillin 24 h prior to first FVT treatment.\n\nResultsSix weeks after first FVT the HF+FVT mice showed a significant decrease in weight gain compared to the HF group. Further, glucose tolerance was comparable between the lean LF and HF+FVT mice, while the other HF groups all had impaired glucose tolerance. These observations were supported by significant shifts in GM composition, blood plasma metabolome, and expression levels of genes involved in obesity and T2D development.\n\nConclusionsTransfer of gut viral communities from mice with a lean phenotype into those with an obese phenotype reduce weight gain and normalise blood glucose parameters relative to lean mice. We hypothesise that this effect is mediated via FVT-induced GM changes.\n\nSignificance of this studyWhat is already known about this subject?\n\nO_LIObesity and type-2-diabetes (T2D) are associated with gut microbiota (GM) dysbiosis.\nC_LIO_LIFaecal microbiota transplant from lean donors has previously shown potential in treating obesity and T2D.\nC_LIO_LIPatients suffering from recurrent Clostridium difficile infections (rCDI) have been cured with sterile filtered donor faeces (containing enteric viruses and no bacteria), here defined as faecal virome transplantation (FVT).\nC_LI\n\nWhat are the new findings?\n\nO_LIFVT from lean donors lead to decreased weight gain and normalised blood sugar tolerance in a diet-induced obesity (DIO) mouse model.\nC_LIO_LIFVT significantly changed the bacterial and viral GM component, as well as the plasma metabolome and the expression profiles of obesity and T2D associated genes.\nC_LIO_LIInitial treatment with ampicillin prior FVT seems to counteract the beneficial effects associated with FVT.\nC_LI\n\nHow might it impact on clinical practice in the foreseeable future?\n\nO_LIWe here show a proof-of-concept, providing a solid base for designing a clinical study of FVT targeting obesity and T2D in humans. This is further augmented by the increased safety related to FVT, since bacteria and other microorganisms are removed from the donor faeces, and therefore minimises the risk of disease transmission.\nC_LIO_LIThese findings highlight the potential application of FVT treatment of various diseases related to GM dysbiosis and further support the vital role of the viral community in maintaining and shaping the GM.\nC_LI

microbiology↗