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A step closer to the perfect poo pill
US researchers have provided a statistical model predicting which bacterial strains will engraft after faecal microbiota transplantation (FMT) treatment for Clostridium difficile. To be successful, donor bacteria must engraft to the recipient’s gut, but the forces influencing engraftment and growth have been largely unknown. Published in Cell Host and Microbe, the article is the first predictive strategy for developing a synthetic probiotic — a biologic therapy based on microorganisms acting as a drug. The scientists studied 20 patients with C. difficile infection who received therapeutic FMT. Using high resolution deep metagenomics genetic sequencing, the scientists studied the gut-level microbiota of donors and recipients before and after FMT up to 4 months. They measured both the strain type and abundance of each strain in donors and recipients to build a predictive model of the presence and the abundance bacterial strains in the recipient after FMT. About 30% of the donor bacteria engrafted in the recipient after FMT, and the most abundant strains were more likely to engraft. From their model, the team showed that the amount of each engrafted strain grown in the recipient could also be predicted. The team developed and applied this model not only to C. difficile patients but in other studies with other diseases, including metabolic syndrome. The researchers also found that recipients acquired new bacteria that were previously undetected in both the donor and the recipient, suggesting that the post-FMT microbiome is a mixture of bacterial strains from the donor, recipient and the environment. In addition, they learned that the recipient microbiome and immune state also have roles in successful FMT. “This [article] provides a context for understanding how to make these live biological therapeutics as an alternative to transferring raw fecal matter,” says cosenior author Eric Alm, codirector of the Center for Microbiome Informatics and Therapeutics at the Massachusetts Institute of Technology.
Single dads more likely to die than single mums or dads in a couple
Single fathers have a higher risk of premature mortality than single mothers and partnered parents, according to an observational study published in Lancet Public Health. The study included 40 490 people who took part in the Canadian Community Health Survey, including 871 single fathers, 4590 single mothers, 16 341 partnered fathers, and 18 688 partnered mothers (average age, 41–46 years). Single parents included people who were living with one or more biological or adopted children under the age of 25 years, and who were divorced, separated, widowed, single, never married, and not living with a partner. The participants completed questionnaires to give details of their lifestyle and sociodemographic status, including their fruit and vegetable intake, physical activity and binge drinking. This was linked to their administrative health records to identify medical conditions, how often they used health services, whether they died, and cause of death. After a median of 11 years’ follow-up, 693 people had died. Single fathers were more likely to die over this period (5.8 deaths per 1000 person-years, 35/871 died), compared with partnered fathers (1.9 deaths per 1000 person-years, 345/16341 died), and single mothers (1.7 deaths per 1000 person-years, 85/4590 died). Partnered mothers were least likely to die over the follow-up period (1.2 deaths per 1000 person-years, 228/18 688 died). At baseline, single fathers were older, had a higher prevalence of cancer than single mothers and partnered parents, and were more likely to have a cardiovascular disease than single and partnered mothers. Single fathers were also more likely than partnered fathers to have had an emergency medical visit or hospital admission in the past year. After adjusting the findings to consider differences in age, lifestyle, health and sociodemographic characteristics, single fathers’ mortality risk over the 11 years of the study was more than two times higher than other parents’. While the leading cause of death for single fathers remained unclear (deaths were most likely classified as “other causes”), single fathers were more likely to lead unhealthy lifestyles. For example, they ate fewer fruit and vegetables and were more likely to binge drink than single mothers and partnered parents. The authors comment that further work is needed to understand the causes of the increased mortality in single fathers.
Stem cell vaccine immunises lab mice against multiple cancers
US researchers report, in Cell Stem Cell, that injecting mice with inactivated induced pluripotent stem cells (iPSCs) launched a strong immune response against breast, lung and skin cancers. The vaccine also prevented relapses in animals that had tumours removed. iPSCs are generated from adult cells genetically reprogrammed to mimic embryonic stem cells’ ability to become any type of cell in the body. In the study, 75 mice received versions of the iPSC vaccine created from iPSCs that have been inactivated by irradiation. Within 4 weeks, 70% of the vaccinated mice fully rejected newly introduced breast cancer cells, while the remaining 30% had significantly smaller tumours. The effectiveness of the iPSC vaccine was also validated for lung and skin cancers. The researchers found that a large amount of the antigens present on iPSCs are also present on cancer cells. When lab mice were vaccinated with iPSCs, their immune systems built an immune response to the antigens on the iPSCs. Because of key similarities between the iPSCs and cancer cells, the animals simultaneously built an immune response against cancer. The iPSCs seemed to prime their immune systems to eradicate tumour cells. To be effective, anticancer vaccines must introduce one or more antigens into the body which activate T cells or produce antibodies capable of recognising and binding to antigens on the surfaces of cancer cells. One of the biggest challenges for cancer immunotherapies is the limited number of antigens that can be presented to the immune system at a given time. The US study uses an animal’s own cells to create an iPSC-based cancer vaccine that simultaneously targets multiple tumour antigens. Using whole iPSCs eliminates the need to identify the most optimal antigen to target in a particular type of cancer.
Early risk of ovarian cancer passed down from fathers
A newly identified mutation, passed down through the X chromosome, is linked to earlier onset of ovarian cancer in daughters and prostate cancer in father and sons according to US research published in PLoS Genetics. In earlier studies, researchers had noticed that when a woman develops ovarian cancer, her sister faces a higher risk of also developing the disease than her mother, an observation that was difficult to explain. This observation led the researchers to investigate whether genes on the X chromosome, potentially passed down through the father, may contribute to his daughters’ risk of ovarian cancer. Using the Familial Ovarian Cancer Registry, the researchers collected information about pairs of granddaughters and grandmothers and sequenced portions of the X chromosome from 186 women affected by the cancer. They found that cases of ovarian cancer linked to genes inherited from the paternal grandmother had an earlier age of onset than cases linked to maternal genes, and were also associated with higher rates of prostate cancer in fathers and sons. Additional sequencing led the researchers to identify a previously unknown mutation on the X chromosome that may be associated with cases of ovarian cancer that develop more than 6 years earlier than average. The study proposes that a gene on the X chromosome may contribute to a woman’s risk of developing ovarian cancer, independently of other known susceptibility genes, such as the BRCA genes. Future studies will be needed, however, to confirm the identity and function of this gene. This observation suggests that there may be many cases of seemingly sporadic ovarian cancer that are actually inherited, and may lead to improved cancer screening and better genetic risk assessment.
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