ORCID Profile
0000-0002-2103-5961
Current Organisations
Wageningen University
,
Danone Nutricia Research (Netherlands)
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Publisher: Informa UK Limited
Date: 06-10-2020
Publisher: Brill
Date: 19-04-2019
DOI: 10.3920/BM2018.0098
Abstract: Beneficial modulation of the gut microbiota is an attractive therapeutic approach to improve the efficacy of vaccine-induced immunity. In this study, mice were supplemented with the prebiotic milk oligosaccharide 2’-fucosyllactose (2’FL) as well as a complex mixture of immune modulatory prebiotic short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides (scGOS/lcFOS) from different stages in early life. Adult mice were vaccinated with trivalent influenza vaccine (TIV) and both development of the gut microbiota and antibody-mediated vaccine responses were followed over time. Within the control group, female mice demonstrated a larger antibody response to TIV vaccination than male mice, which was accompanied by enhanced cytokine production by splenocytes and a higher percentage of plasma cells in skin draining lymph nodes. In addition, the prebiotic diet improved vaccine-specific antibody responses in male mice. Introduction of prebiotics into the diet modulated the gut microbiota composition and at the genus level several bacterial groups showed a significant interaction effect which potentially contributed to the immunological effects observed. This study provides insight in the effect of scGOS/lcFOS/2’FL in influenza vaccination antibody production.
Publisher: American Society for Microbiology
Date: 04-2005
DOI: 10.1128/JB.187.7.2377-2385.2005
Abstract: Two genes, gusB and gusC , from a natural fecal isolate of Escherichia coli are shown to encode proteins responsible for transport of β-glucuronides with synthetic [ 14 C]phenyl-1-thio-β- d -glucuronide as the substrate. These genes are located in the gus operon downstream of the gusA gene on the E. coli genome, and their expression is induced by a variety of β- d -glucuronides. Measurements of transport in right-side-out subcellular vesicles show the system has the characteristics of secondary active transport energized by the respiration-generated proton motive force. When the genes were cloned together downstream of the tac operator-promoter in the plasmid pTTQ18 expression vector, transport activity was increased considerably with isopropylthiogalactopyranoside as the inducer. Amplified expression of the GusB and GusC proteins enabled visualization and identification by N-terminal sequencing of both proteins, which migrated at ca. 32 kDa and 44 kDa, respectively. Separate expression of the GusB protein showed that it is essential for glucuronide transport and is located in the inner membrane, while the GusC protein does not catalyze transport but assists in an as yet unknown manner and is located in the outer membrane. The output of glucuronides as waste by mammals and uptake for nutrition by gut bacteria or reabsorption by the mammalian host is discussed.
Publisher: Springer Science and Business Media LLC
Date: 23-05-2023
DOI: 10.1038/S41419-023-05850-9
Abstract: Cytotoxicity (i.e. cell death) is the core mechanism by which chemotherapy induces its anti-cancer effects. Unfortunately, this same mechanism underpins the collateral damage it causes to healthy tissues. The gastrointestinal tract is highly susceptible to chemotherapy’s cytotoxicity, resulting in ulcerative lesions (termed gastrointestinal mucositis, GI-M) that impair the functional capacity of the gut leading to diarrhea, anorexia, malnutrition and weight loss, which negatively impact physical sychological wellbeing and treatment adherence. Preventing these side effects has proven challenging given the overlapping mechanisms that dictate chemotherapy efficacy and toxicity. Here, we report on a novel dietary intervention that, due to its localized gastrointestinal effects, is able to protect the intestinal mucosal from unwanted toxicity without impairing the anti-tumor effects of chemotherapy. The test diet (containing extensively hydrolyzed whey protein and medium chain triglycerides (MCTs)), was investigated in both tumor-naïve and tumor-bearing models to evaluate its effect on GI-M and chemo-efficacy, respectively. In both models, methotrexate was used as the representative chemotherapeutic agent and the diet was provided ad libitum for 14 days prior to treatment. GI-M was measured using the validated biomarker plasma citrulline, and chemo-efficacy defined by tumor burden (cm 3 /g body weight). The test diet significantly attenuated GI-M ( P = 0.03), with associated reductions in diarrhea ( P 0.0001), weight loss ( P 0.05), daily activity ( P 0.02) and maintenance of body composition ( P 0.02). Moreover, the test diet showed significant impact on gut microbiota by increasing ersity and resilience, whilst also altering microbial composition and function (indicated by cecal short and brained chain fatty acids). The test diet did not impair the efficacy of methotrexate against mammary adenocarcinoma (tumor) cells. In line with the first model, the test diet minimized intestinal injury ( P = 0.001) and diarrhea ( P 0.0001). These data support translational initiatives to determine the clinical feasibility, utility and efficacy of this diet to improve chemotherapy treatment outcomes.
No related grants have been discovered for Jan Knol.