News Round-up
Intestinal Bacteria from Healthy Infants Prevent Food Allergy
Study shows gut microbes from healthy infants prevent the development of cows’ milk allergy when transplanted into mice.
New research shows that healthy infants have intestinal bacteria that prevent the development of food allergies.
Researchers from the University of Chicago, Argonne National Laboratory and the University of Naples Federico II in Italy found that when gut microbes from healthy human infants were transplanted into germ-free mice, the animals were protected from an allergic reaction when exposed to cows' milk. Gut microbes from infants allergic to milk did not offer the same protection; mice receiving these bacteria suffered an allergic reaction when given cows’ milk. Cows' milk allergy is the most common food allergy affecting children.
The study, published in Nature Medicine, also identifies a specific bacterial species that protects against allergic responses to food. "This study allows us to define a causal relationship and shows that the microbiota itself can dictate whether or not you get an allergic response," said Cathryn Nagler, PhD, the Bunning Food Allergy Professor at UChicago and senior author of the study.
The research, funded in part by the National Institute of Allergy and Infectious Diseases, is the result of a long collaboration between Nagler and Roberto Berni Canani, MD, PhD, Chief of the Pediatric Allergy Program and CEINGE Advanced Biotechnologies at the University Federico II of Naples, Italy. In 2015, the two worked together on a project that found significant differences in the gut microbiomes of healthy infants and those with cows' milk allergy. That eventually led them to ask if those differences somehow contributed to the development of the allergy.
The researchers transplanted gut microbes from each of eight infant donors – four healthy and four with cows’ milk allergy – into groups of mice via faecal samples. The mice had been raised in a completely sterile, germ-free environment, meaning they had no bacteria of their own. The mice were fed the same formula as the infants to help the bacteria colonise properly by providing the same sources of nutrients.
Mice that received bacteria from allergic infants suffered from anaphylaxis, a life-threatening allergic reaction, when exposed to cows' milk for the first time. Germ-free control mice that were not given any bacteria also experienced this severe reaction. Those that received healthy bacteria appeared to be completely protected, however, and did not suffer an allergic reaction.
"These findings demonstrate the critical role of the gut microbiota in the development of food allergy and strongly suggest that modulating bacterial communities is relevant to stopping the food allergy disease burden," Canani said. "These data are paving the way for innovative interventions for the prevention and treatment of food allergy that are under evaluation at our Centres."
The researchers also studied the composition of microbes in the intestinal tract of the mice and analysed differences in gene expression between the healthy and allergic groups. This allowed them to pinpoint a particular species, Anaerostipes caccae, that appears to protect against allergic reactions when it is present in the gut.
A.caccae is part of a class of bacteria, Clostridia, that Nagler and her colleagues identified in a 2014 study that protects against nut allergies. These bacteria produce butyrate, a short-chain fatty acid that previous research has shown is a crucial nutrient for establishing a healthy microbial community in the gut. This suggests that this class of butyrate-producing bacteria provides more general protection against other common food allergies as well. These bacteria or their metabolites could be used as part of biotherapeutic drugs to prevent or reverse other common food allergies.
"What we see with this work again is how, in the context of all of the different types of microorganisms inhabiting the gastrointestinal tract, one single organism can have such a profound effect on how the host is affected by dietary components," said Dionysios Antonopoulos, PhD, Microbial Systems Biologist at Argonne, Assistant Professor of Medicine at UChicago and a co-author of the study. "We also get a new appreciation for the distinct roles that each of these members play beyond the generalisation that the 'microbiome' is involved."
Feehley T, et al. (2019). Healthy infants harbor intestinal bacteria that protect against food allergy. Nature Medicine; https://doi.org/10.1038/s41591-018-0324-z
First Rare Disease Collaborative Network on Refractory Coeliac Disease Commissioned
Refractory coeliac disease, a deadly form of the autoimmune condition coeliac disease, receives its first dedicated support from NHS England with the setting up of a Rare Disease Collaborative Network (RDCN) to accelerate research and treatment into this life-threatening condition.
Coeliac disease is relatively common with one in 100 people in the UK experiencing the condition and can be successfully treated with a gluten-free diet for life. Refractory coeliac disease affects 2 to 5% of these patients. They do not get better on a gluten-free diet and are more likely to develop a specific type of cancer with fatal consequences. Professor David Sanders from Sheffield will lead the Network, working alongside Dr Jeremy Woodward at the collaborating centre in Cambridge. The RDCN will be looking to drive improvements in patient outcomes through greater understanding of refractory coeliac disease.
Professor David Sanders said: “The outlook for patients with refractory coeliac disease has been very poor, with 50% life expectancy post five years. The support from NHS England is wonderful as it will allow us an opportunity to collectively work on improving this awful situation for our patients.”
RDCNs have been set up by the Government recently as part of its Strategy for Rare Diseases with a vision to lead to improved outcomes for patients with very rare diseases which have a prevalence of <1 in 10,000 of the population.
Earlier this year Coeliac UK, the largest independent charity for people who need to live gluten free, launched a research fund and accompanying fundraising appeal, aiming to raise £5 million to change the future for people with coeliac disease and gluten-related autoimmune conditions.
Sarah Sleet, Chief Executive of Coeliac UK, said: “This is the first time refractory coeliac disease will receive the focus from NHS England on new treatments and care that is so desperately needed. Now that we have this crucial recognition, we are working through our Research Fund to ensure we can make the investment and capitalise on this development and help improve the future for patients suffering with debilitating symptoms and we are delighted that Prof Sanders and Dr Woodward will be leading this collaborative network.”
For further information: www.coeliac.org.uk/researchfund
Are you a super pooper?
Poop transplants have become routine treatment for nasty recurrent diarrheal infections, but trials for other conditions have hit a bum note. Now, the faecal faithful have re-examined the evidence.
Time and again, they found one donor whose stool was substantially more likely to lead to clinical improvement than others in the same trial. These 'super-donors' can provide the necessary bacteria to restore gut chemicals that are lacking in illnesses like IBD and diabetes, according to a new review published in Frontiers in Cellular and Infection Microbiology. With Alzheimer's, multiple sclerosis, cancers, asthma, allergies and heart disease all associated with changes to gut bacteria as well, understanding what makes a faecal super donor could make poop the new panacea.
Faecal transplants from super donors have high success rates
"The last two decades have seen a growing list of medical conditions associated with changes in the microbiome – bacteria, viruses and fungi, especially in the gut," says senior author Dr Justin O'Sullivan of the University of Auckland.
"In fact, we know already that changes to the gut microbiome can contribute to disease, based on studies in germ-free mice as well as clinical improvement in human patients following restoration of the gut microbiome by transplanting stool from a healthy donor."
While the overall cure rate for recurrent diarrhoeal infection exceeds 90%, trials of faecal transplantation for other conditions like inflammatory bowel disease exacerbations and type 2 diabetes have had much more mixed results, averaging nearer 20%.
"The pattern of success in these trials demonstrates the existence of 'super-donors', whose stool is particularly likely to influence the host gut and to lead to clinical improvement," explains O'Sullivan.
"We see transplants from super-donors achieve clinical remission rates of perhaps double the remaining average. Our hope is that if we can discover how this happens, then we can improve the success of faecal transplantation and even trial it for new microbiome-associated conditions like Alzheimer's, multiple sclerosis and asthma."
Super stool is rich in bacteria that enhance our metabolism
O'Sullivan and colleagues reviewed faecal transplantation trials for clues to the origin of the super-donor phenomenon.
"It is well-known that responders typically exhibit a higher microbial diversity than non-responders. In line with these observations, a larger number of species in the donor stool has been shown to be one of the most significant factors influencing faecal transplantation outcome," O'Sullivan explains.
In particular, super donor stool tends to have high levels of specific 'keystone species'. These are bacteria which produce chemicals whose lack in the host gut contributes to disease.
"In inflammatory bowel disease and diabetes for example, keystone species that are associated with prolonged clinical remission produce butyrate – a chemical with specialised functions in regulating the immune system and energy metabolism."
The keystone species theory can be tested, of course, by selecting donor stool rich in particular strains – or by designing 'precision' transplants with a defined mixture of beneficial bacteria, like a probiotic.
"This approach has been applied successfully to prevent complications in a small sample of patients with liver disease. However, this study showed that microbial enrichment in the donor does not completely guarantee enrichment in the recipient."
Viruses, immunity and diet also influence faecal transplant success
Clearly, there is more to super-donors than keystone species.
The balance of other bacteria present, and the interactions between them, seems to influence the retention of keystone species.
But digging deeper into stool samples, the researchers have discovered that it matters not only which bacteria are present, but what's present in and around the bacteria.
"For example, the success of faecal transplants has been associated in some studies with the transfer of viruses which infect other gut microbes. Some cases of recurrent diarrhoeal infection have even been cured with transplants of filtered stool, that has had all the live bacteria filtered out but still contains DNA, viruses and other debris.
These viruses could affect the survival and metabolic function of transplanted bacteria and other microbes."
Abandoning the ‘one stool fits all’ approach
Ultimately, O'Sullivan and colleagues acknowledge that super-donors may not fully account for successful faecal transplantation.
"Some faecal transplant failures may be attributable to the gut's immune response to transplanted microbes, possibly stemming from an underlying genetic difference between the donor and the recipient.
Supporting the transplanted microbiome through diet could also improve success. It has been shown that a rapid change in diet, such as a switch from an animal-based to an exclusively plant-based diet, can alter the composition of the gut microbiota within 24 hours."
They recommend that future faecal transplant trials routinely record information on the genetic background and dietary intake of recipients, so that we can better understand their impact on transplant engraftment and clinical remission.
Wilson BC, et al. (2019). The Super-Donor Phenomenon in Fecal Microbiota Transplantation. Front. Cell. Infect. Microbiol.; https://doi.org/10.3389/fcimb.2019.00002
Study Shows Low-sugar Diet Effective in Boys with Non-alcoholic Fatty Liver Disease
Researchers at University of California San Diego School of Medicine and Emory University School of Medicine found that a diet low in free sugars (those added to foods and beverages and occurring naturally in fruit juices) resulted in significant improvement in non-alcoholic fatty liver disease (NAFLD) in adolescent boys.
The study was published in the January 22 issue of JAMA.
NAFLD is the most common liver disease in children and is associated with type 2 diabetes, end-stage liver disease, liver cancer and cardiovascular disease. “With more than five million children having NAFLD, this is a disease that is much more common and serious than most people are aware of. An effective treatment is crucial for long-term health,” said lead author Jeffrey Schwimmer, MD, professor of clinical paediatrics at UC San Diego School of Medicine. “Although there is enormous controversy about diet, we know that sugar can play a strong role in the development of liver fat. Our study targeted free sugar based upon a combination of the biology of NAFLD and the real-world practicality of a diet that is achievable and that could be an effective treatment.”
The study included 40 boys ages 11 to 16 with diagnosed NAFLD. The participants were randomised into two groups. Half of the boys, along with their families, were provided a diet low in free sugars (less than 3% of daily caloric intake), and half ate their usual diets for eight weeks. Reducing sugars in the diet involved decreasing glucose, fructose and sucrose commonly consumed in sweetened foods and beverages and in naturally sweet fruit juices.
Researchers interviewed the participants and their families, took inventory of the food in their home and removed food that did not meet study requirements. The research team helped the families plan meals, grocery shop, cook and prep meals. The diet was for the entire family and was designed to be as similar as possible to their regular diet, minus the sugar.
“Although paediatric guidelines for managing non-alcoholic fatty liver disease recommend a healthy diet, focused reduction of sugary foods and beverages was an unproven treatment,” said senior author Miriam Vos, MD, MSPH, professor of paediatrics at Emory.
The study sought to measure change in liver fat at baseline and after eight weeks of therapy, based on magnetic resonance imaging proton density fat fraction measurement – a state-of-the-art method to quantify lipids in the liver that was developed at UC San Diego. The researchers found that the boys in the low-free sugar diet group had a reduction in liver fat of 31% on average, while the boys in the typical diet group showed no improvement. Blood test measures of liver inflammation also indicated significant improvement for children in the low-free sugar group compared to the typical diet group.
“The substantial improvement seen in just eight weeks makes us believe that a diet low in free sugars has the potential be a clinically relevant treatment,” said Schwimmer. “The next steps will be to take what we have learned and test this approach in a way that empowers families to control the diet themselves for a long enough time to see if we can effectively treat NAFLD and prevent cirrhosis, liver failure and liver cancer.”
BSNA Response to NHS England Guidance on Prescribing Gluten-free Foods in England
NHS England has published guidance for Clinical Commissioning Groups (CCGs) on the prescribing of gluten-free foods in primary care in England. This follows the Department of Health & Social Care (DHSC) consultation outcome, to continue to allow access to gluten-free foods on prescription in England but to restrict items to gluten-free bread products and mixes only.
The British Specialist Nutrition Association (BSNA) is pleased to see that the NHS England guidance acknowledges the postcode lottery which currently exists across England and has made it their objective to provide clear national advice to make local prescribing practices more effective. We welcome the acknowledgement within the guidance, that the provision of gluten-free bread and mixes on NHS prescription is expected to minimise any drop in adherence.
Declan O’ Brien, Director General of the British Specialist Nutrition Association, said: “We welcome that NHS England expects bread products and mixes to be provided on prescription in England for all patients diagnosed with coeliac disease or dermatitis herpetiformis. However, we are concerned that the contradictory statements within the guidance may lead to more confusion amongst prescribers and more uncertainty for patients.
We remain optimistic that every CCG will see the benefit for patients and follow the National Guidance to align with this expectation.”
The changes to gluten-free prescribing can be read here.