Gut microbiome and IBD – the connection maybe in diet says study

By Dr. Ananya Mandal, MDSep 10 2019

A new study has shown conclusive evidence that inflammatory bowel disease or IBD is intimately associated with the gut microbial environment which can be altered with prescription diet. The microbiome within the human gut is a collection of healthy and helpful bacteria that help in several functions of the body including development and maintenance of immunity. Diet and several other factors such as regular intake of drugs affect the health of the gut microbiome. Researchers from the University of Pennsylvania looked at the association of diet, gut microbiome and IBD. Their paper titled, “Diet-induced remission in chronic enteropathy is associated with altered microbial community structure and synthesis of secondary bile acids,” was published in the journal Microbiome.

Dogs and humans with IBD

Daniel Beiting, senior author of the study and assistant professor in Penn's School of Veterinary Medicine, in a statement said, “The bacteria in the gut are known to be a really important factor in tipping the scales toward disease. And the environmental factor that seems to contribute the most to rapid changes in the microbiome is what you eat. Given that dogs' microbiomes are extremely similar to those of humans, we thought this was an intriguing model to ask, 'Could diet be impacting this disease through an impact on the microbiome?” To address this hypothesis they studied dogs with canine chronic enteropathy (CE), that led to Crohn’s disease like features in the dogs including diarrhea, vomiting, loss of appetite, weight loss, gut inflammation that kept coming back etc.

Tracking dogs on a prescription diet for an intestinal disease, researchers found that those that responded well shared a suite of changes to their microbiome. (Image: Penn Vet)

Study design

The researchers wrote that theirs was a prospective study that looked at “16S rRNA gene amplicon sequencing, metagenomic sequencing” or genetic sequencing of the bacteria in the stool, “metabolomic profiling” or looking at the metabolic end products in the stool of the dogs and clinical monitoring of the dogs. They also looked at the growth of the bacteria in the lab and their effects on the mice models of IBD.

The team looked at the effect of a prescription tailor-made diet or “hydrolysed protein diet” and the gut microbiome. They studied 29 dogs with CE at the Penn Vet's Ryan Veterinary Hospital were undergoing treatment for IBD using medications as well as prescription diets. They compared the results with 24 healthy control dogs as well to avoid bias. Stool samples of the dogs were collected and analyzed for metabolic products as well as for gut microbes. The microbes were determines using high end genetic testing for the microbe DNA in the dog stool. According to Beiting, collecting information on the microbes as well as metabolic products was a move directed to make the study more robust. He said, “That gives us a functional read-out of the microbiome. It doesn't just tell us who is there but also what they're doing.”

Study results with dogs

They noted that certain diets lead to specific metabolic end products in the dogs that showed improvement. They found that 20 of the 29 dogs with CE entered remission when prescribed a specific diet. These metabolic products were produced by certain gut microbes only. This meant that the compounds called the secondary bile acids were actually caused by the healthy gut microbes which in turn caused improvement in the CE symptoms.

The secondary bile acids produced by the gut microbes were actually due to the metabolism of the bile hat these specific microbes consume, write the researchers. These friendly bacteria they explain include Clostridium hiranonis. The team explained that these bacteria were higher among the stool samples of dogs that showed remission from their symptoms. Harmful bacteria included Escherichia coli and Clostridium perfringens which decreased in number when the diet was altered and the dogs went into remission from their symptoms. Shuai Wang, a postdoc at Penn Vet and the study's lead author explained that then they took samples of these bacteria from dogs in remission before and after their symptoms improved and grew them in the labs. Wang said, “Having these organisms gave us the opportunity to test our hypothesis about what actually causes remission.”

Lab research on type of bacteria in the dog stool samples

To further prove their point they took the secondary bile acids from the dogs in remission and used them on growths of harmful bacteria such as E coli and C prefringens. These secondary bile acids successfully inhibited the growth of harmful bacteria in the labs the team explained. This proved that the secondary bile acids from the friendly bacteria helped reduce harmful bacteria.

Lab research on mice with IBD

The team also replicated their findings among lab mice to prove their hypothesis. They took the good bacteria C. hiranonis from the dogs in remission and introduced them into mice with IBD like disorders. Wang explained, “We observed a stabilization of secondary bile acid levels and reduced inflammation.” Beiting added, “This allowed us to show that secondary bile acids and C. hiranonis aren't just biomarkers of remission... they can actually effect change. Bile acids can block the growth of pathogens, and C. hiranonis can improve gut health in mice.”

Study on humans with IBD

As an additional proof in humans the team examined data from children with Crohn’s disease who were prescribed a liquid enteral diet. Those children in remission had more of Clostridium scindens bacteria in their stool compared to those not in remission, they noted. C scindens, the team wrote is another bacterial species that is capable of producing secondary bile acids. Robert N. Baldassano, co-author and pediatric gastroenterologist at Children's Hospital of Philadelphia said, “Similar environmental exposures of dogs and children make the canine IBD model an excellent model of pediatric inflammatory bowel disease. This study has greatly improved our knowledge of pediatric IBD and will lead to new therapies for children suffering with this disease.”

Conclusions

The authors concluded, “These data show that remission induced by a therapeutic hydrolyzed protein diet is linked to improved microbiota structure in canine chronic inflammatory enteropathy, marked by decreased relative abundance of pathobionts and increased abundance of a secondary bile acid producer (C. hiranonis).” They wrote, “Mining public data from diet therapy in human pediatric Crohn’s disease showed similar results, supporting a model by which dietary interventions lead to remission.” They ended by saying, “These results warrant further investigations in other animal models and human studies and constitute an important first step in establishing a framework for evaluating the efficacy of dietary interventions, which could help guide the rational design of more effective therapeutic diets.”