London, England : British Broadcasting Corporation (BBC), 2012.
Video — 1 online resource (50 min.)
Get an inside view - You may be pretty familiar with what you look like from the outside, but in Guts presenter Michael Mosley gets up close and personal with his own digestive system to reveal what we look like inside. Guts uncovers the secret life of our digestive tract In an eye-opening and detailed exploration of a part of the body we normally never get to see. Using the latest in medical imagery and a tiny state of the art camera 'pill' that he swallows at the start of the film, Mosley takes viewers on a remarkable journey through his own internal system. At each stage he talks to medical experts and explains the amazing functions that happen without our conscious effort. This is one of the most fundamental parts of our bodies, controlled by its own nervous system and automatically providing our energy, water and nutrients -- yet unless we get sick, we rarely think about what it's doing. Thanks to this fascinating documentary, that's all about to change. Guts is a BBC science documentary which allows viewers to explore the inner workings of our digestive systems.
The intestinal epithelium is one of the most rapidly proliferating tissues in the body. A complete turnover of the epithelium occurs every 3-5 days in the mouse, a process that is maintained by a small population of intestinal stem cells (ISCs) that reside in the crypt bases. The signals that regulate the behavior of these ISCs are still poorly understood. However, the recent identification of genes that mark functional stem cells has yielded insights into how ISCs are regulated and maintained. Here, we demonstrate that Bmi1 and Lgr5 mark two functionally distinct ISCs in vivo. Lgr5 marks mitotically active ISCs that exhibit exquisite sensitivity to canonical Wnt modulation, contribute robustly to homeostatic regeneration, and are quantitatively ablated by irradiation. In contrast, Bmi1 marks quiescent ISCs that are insensitive to Wnt perturbations, contribute weakly to homeostatic regeneration, and are resistant to high dose radiation injury. Post-irradiation, however, the normally quiescent Bmi1+ ISCs dramatically proliferate to clonally repopulate multiple contiguous crypts and villi. Clonogenic culture of isolated single Bmi1+ ISCs yields long-lived self-renewing spheroids of intestinal epithelium that produce Lgr5-expressing cells, thereby establishing a lineage relationship between these two populations in vitro. Taken together, these data provide direct evidence that Bmi1 marks quiescent, injury-inducible reserve ISCs that exhibit striking functional distinctions from Lgr5+ ISCs, and support a model whereby distinct ISC populations facilitate homeostatic versus injury-induced regeneration. How these ISCs maintain their stemness remains unclear. Paneth cells have been suggested to serve as niche cells for the Lgr5+ ISCs, perhaps through the secretion of essential paracrine factors, but recent reports clearly demonstrate that Paneth cells are not required for Lgr5+ ISC maintenance. Recently, the G-protein-coupled receptors Lgr4-6 were reported to associate with Wnt receptors to mediate R-spondin signaling. Given the importance of Wnt/R-spondin signaling in intestinal crypt maintenance, we tested the in vivo function of Lgr5 by adenovirus-mediated overexpression of the soluble ligand-binding Lgr5 extracellular domain. Circulating Lgr5 ectodomain induced the migration of Paneth cells from the crypts, their eventual loss, and a concomitant disappearance of Lgr5+ ISCs. Paneth cell migration was associated with downregulation of Wnt signaling and its target EphB3. The loss of Lgr5+ ISCs did not affect maintenance of the intestinal epithelium, nor did Lgr5+ stem cells disappear from non-intestinal organs. Together, these findings characterize an easily tractable experimental model for the in vivo deletion of Lgr5+ ISCs, and suggest that Lgr receptors function to actively maintain Lgr5+ ISCs in vivo.
Each week around 80 Australians die from preventable bowel cancer. Dr Maryanne Demasi reports on the threat to end the lifesaving screening program and the doctors calling for the program to be continued and expanded.
The importance of the intestinal microbiota to the health of an organism is well recognized. Alterations in the composition of the microbiota are associated with a number of diseases. However, the extent to which the microbiota varies across healthy individuals and time and the causes of this variation are still not fully understood. In order to distinguish between microbial community states of health and disease, the range of healthy microbial communities must be determined. In addition, the effect of perturbations on the microbiota is an area of active research. Recent studies indicate that intestinal infections can have a significant impact on the composition of intestinal microbiota. However, the extent and duration of these changes during different infections have not been fully characterized. My aims were to characterize the range of healthy microbiota in an inbred mouse population over time and to determine the dynamics of alterations in the microbiota during disease. I also wanted to determine if certain characteristics of the microbiota make animals more or less susceptible to infection. In this work, 46 individual healthy mice were sampled over time to assess the range of microbial communities in health. A mouse model of Salmonella enterica serovar Typhimurium infection was used to assess the impact of infection on the microbiota. Mice were sampled prior to infection and over the course of infection. This work finds that the microbiota of healthy mice varies significantly over time and among individuals. However, there are stable differences among individual mice, which may be established at the point of weaning when adult microbial communities develop. In addition, this work finds significant changes in the microbiota during infection that differ with the level of infection. This data also shows that there are some taxa whose abundance prior to infection correlates with outcome of infection. This work provides insights into the dynamics of the microbiota in health and disease and its impact on the health of the host.