BackgroundIntervention strategies for obesity are global issues that require immediate attention. One approach is to exploit the growing consensus that beneficial gut microbiota could be of use in intervention regimes. Our objective was to determine the mechanism by which the probiotic bacteria Lactobacillus paracasei ssp paracasei F19 (F19) could alter fat storage. Angiopoietin-like 4 (ANGPTL4) is a circulating lipoprotein lipase (LPL) inhibitor that controls triglyceride deposition into adipocytes and has been reported to be regulated by gut microbes.Methodology/Principal FindingsA diet intervention study of mice fed high-fat chow supplemented with F19 was carried out to study potential mechanistic effects on fat storage. Mice given F19 displayed significantly less body fat, as assessed by magnetic resonance imaging, and a changed lipoprotein profile. Given that previous studies on fat storage have identified ANGPTL4 as an effector, we also investigated circulating levels of ANGPTL4, which proved to be higher in the F19-treated group. This increase, together with total body fat and triglyceride levels told a story of inhibited LPL action through ANGPTL4 leading to decreased fat storage. Co-culture experiments of colonic cell lines and F19 were set up in order to monitor any ensuing alterations in ANGPTL4 expression by qPCR. We observed that potentially secreted factors from F19 can induce ANGPTL4 gene expression, acting in part through the peroxisome proliferator activated receptors alpha and gamma. To prove validity of in vitro findings, germ-free mice were monocolonized with F19. Here we again found changes in serum triglycerides as well as ANGPTL4 in response to F19.Conclusions/SignificanceOur results provide an interesting mechanism whereby modifying ANGPTL4, a central player in fat storage regulation, through manipulating gut flora could be an important gateway upon which intervention trials of weight management can be based.

Chronic inflammation is increasingly recognized as a major contributor of human colorectal cancer (CRC). While gut microbiota can trigger inflammation in the intestinal tract, the precise signaling pathways through which host cells respond to inflammatory bacterial stimulation are unclear. Here, we show that gut microbiota enhances intestinal tumor load in the APC(Min/+) mouse model of CRC. Furthermore, systemic anemia occurs coincident with rapid tumor growth, suggesting a role for intestinal barrier damage and erythropoiesis-stimulating mitogens. Short-term stimulation assays of murine colonic tumor cells reveal that lipopolysaccharide, a microbial cell wall component, can accelerate cell growth via a c-Jun/JNK activation pathway. Colonic tumors are also infiltrated by CD11b+ myeloid cells expressing high levels of phospho-STAT3 (p-Tyr705). Our results implicate the role of gut microbiota, through triggering the c-Jun/JNK and STAT3 signaling pathways in combination with anemia, in the acceleration of tumor growth in APC(Min/+) mice.

SummarySeparating the large intestine from gut flora is a robust layer of epithelial cells. This barrier is armed with an array of recognizing receptors that collectively set the host innate response. Here, we use nuclear receptors (NRs) and Toll-like receptors (TLRs), suggested to act as second messengers in the communication between microorganisms and epithelial cells, as probes to assess the impact of gut flora on innate immunity in germ-free (GF) mice. Using quantitative real-time polymerase chain reaction analyses, we show that 37/49 NRs are expressed in colonic cells of GF mice. Of these, 5 can be modulated by resident flora: LXRa, RORg and CAR show reduced expression and Nur77 and GCNF display elevated expression in conventionally raised mice compared with GF. Moreover, increased expression levels of TLR-2 and TLR-5 are observed in specific pathogen-free (SPF) mice compared with GF mice, and CAR expression is connected to the TLR-2 signalling pathway. Infections of GF or SPF mice with Yersinia pseudotuberculosis, show that GF intestinal epithelial cells fail to respond, except for CAR, which is downregulated. In contrast, SPF epithelial cells show a downregulation of all the NRs except CAR, which appears to be unaffected. Our findings indicate that gut flora contributes to the development of an intact barrier function.

The postembryonic development of the gastrointestinal tract is subject to regulation by the colonizing microbiota. This maturation process requires the commensal bacteria to cross-talk with host cells by way of recognizing receptors and inducing signaling pathways to activate transcription factors such as the nuclear receptors. Here, we show that in colonic cell lines and in primary colonic cells, Enterococcus faecalis isolated from newborn babies possess the ability to regulate peroxisome proliferator-activated receptor-␥1 (PPAR␥1) activity through phosphorylation. This results in elevated DNA binding and transcriptional activation of downstream target genes, including IL-10, a cytokine known to modulate innate immune function. Furthermore, phosphorylation appears tightly regulated as phospho-PPAR␥1 becomes an immediate substrate for degradation possibly to curtail any extended transactivation. The involvement of PPAR␥1 in a myriad of physiological processes further confirms that microflora-driven regulation might be important for a number of homeostatic strategies in the gut.microbe-host interaction ͉ nuclear receptors ͉ transcription

Purpose To explore, through a learning activity for healthcare students, how patients perceived the ward round and its patient-centered approach. Patients and Methods Patients admitted for elective orthopedic surgery were invited to participate in the study, which involved answering a survey comprising seven intersectional questions and eight free text questions. In addition, medical and nursing students did semi-structured interviews with the patients, covering the same free text questions. Twenty-three patients answered the survey, of whom fifteen also completed the interviews. The results from the interviews were explored using a thematic content analysis. Results Forty-three percent (10/23) of the patients strongly agreed or agreed that their knowledge of patient-centered ward round was sufficient to be able to participate actively, and thirty percent (7/23) indicated they had good knowledge of the laws and regulations governing the care of patients. Most of the patients felt satisfied with how their own and their relatives’ experiences were taken into account. The categories information and to be listened to were mentioned repeatedly by patients as priorities for patient-centered ward rounds. The interview analysis revealed four main categories: preparation, communication, organization, and safety as important and in need of improvement. Conclusion Less than half of the patients surveyed felt they could participate in the ward round, which indicates that there is an opportunity for improvement and development. Better information and communication about legal rights, as well as about the structure and content of the ward round, could be valuable to patients before admission. It is also important to find a way for patients’ individual wishes to be more fully and easily conveyed to medical staff. Creating a more tailor-made ward round for each patient and fulfilling a patient-centered approach will likely entail a substantial organizational and mental shift.