Project description:Flagellins from commensal bacteria can be weak Toll-like receptor (TLR)5 agonists despite high affinity binding to TLR5, ligands we termed “silent flagellins”. To determine if silent flagellins are detectable in the human gut, endogenous flagellins produced by the microbiota were isolated from stool obtained from a healthy adult female donor. TLR5 was used as bait to enrich for silent flagellins and TLR5-bound flagellins were identified by searching peptides against a custom flagellin database built from metagenome sequences.
Project description:Background:
- Some bacteria found in the large and small intestines help keep people healthy and aid digestion. They may also affect a person s risk of developing cancer. Researchers want to study the relationship between intestinal bacteria and breast cancer risk factors. They can do this by looking at stool and urine samples from postmenopausal women.
Objectives:
- To study intestinal bacteria and its relationship to urine-based markers of breast cancer risk in women.
Eligibility:
- Women between 55 and 69 years of age with a recent mammogram that showed no signs of cancer.
Design:
* Participants will be screened with a medical history and basic health questionnaire.
* At home, participants will complete questionnaires about cancer risk factors and food consumption.
* Participants will also collect urine and stool samples. They will send the samples to the designated labs for study.
* No treatment will be provided as part of this protocol.
Project description:Some commensal bacteria stimulate the immune system but do not present specific antigenicity. Such adjuvant effects have been reported for the bacterial species Lactobacillus plantarum. To study in vivo human responses to L. plantarum, a randomised double-blind placebo-controlled cross-over study was performed. Healthy adults were provided preparations of living and heat-killed L. plantarum bacteria, biopsies were taken from the intestinal mucosa and altered transcriptional profiles were analysed. Transcriptional profiles of human epithelia displayed striking differences upon exposure to living L. plantarum bacteria harvested at different growth phases. Modulation of NF-κB-dependent pathways was central among the major altered cellular responses. This unique in vivo study shows which cellular pathways are associated with the induction of immune tolerance in mucosal tissues towards common adjuvanticity possessing lactobacilli. Keywords: mucosal response of healthy adult humans to lactic acid bacteria
Project description:Probiotic bacteria, specific representatives of bacterial species that are a common part of the human microbiota, are proposed to deliver health benefits to the consumer by modulation of intestinal function via largely unknown molecular mechanisms. To explore in vivo mucosal responses of healthy adults to probiotics, we obtained transcriptomes in an intervention study following a double-blind placebo-controlled cross-over design. In the mucosa of the proximal small intestine of healthy volunteers, probiotic strains from the species Lactobacillus acidophilus, L. casei and L. rhamnosus each induced differential gene regulatory networks and pathways in the human mucosa. Comprehensive analyses revealed that these transcriptional networks regulate major basal mucosal processes, and uncovered remarkable similarity to response profiles obtained for specific bioactive molecules and drugs. This study elucidates how intestinal mucosa of healthy humans perceive different probiotics and provides avenues for rationally designed tests of clinical applications. Keywords: mucosal response of healthy adult humans to lactic acid bacteria
Project description:Disrupted interactions between host and intestinal bacteria are implicated in the development of colorectal cancer (CRC). However, the functional impacts of these inter-kingdom interactions remain poorly defined. To examine this interplay, we performed small RNA sequencing on the stool of from germ-free (GF) and gnotobiotic ApcMin/+;Il10-/- mice associated with microbes from biofilm-positive human CRC tumor (BT) and biofilm-negative healthy (BX) tissues. revealed a group of significant differentially expressed miRNAs specific to BT compared to BX associated ApcMin/+;Il10-/- mice and several miRNAs that correlated with bacterial genera abundances. Our findings suggest complex interactions within bacterial communities affecting host-derived miRNA and CRC development.