Category Archives: Dogs

The diet-microbiome connection in inflammatory bowel disease

Much remains mysterious about the factors influencing human inflammatory bowel disease (IBD), but one aspect that has emerged as a key contributor is the gut microbiome, the collection of microorganisms dwelling in the intestines.

Diet is known to profoundly affect this microbial community, and special diets have been used as therapies for intestinal disorders including Crohn’s disease in people. They’re also commonly used in dogs, which can develop a chronic intestinal disease that mirrors many features of Crohn’s.

Beiting-diet-IBD

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)

In a new study published in the journal Microbiome, researchers from the University of Pennsylvania investigated the connection between a prescription diet, the gut microbiome, and a successful entry into disease remission in pet dogs receiving treatment at Penn Vet’s Ryan Veterinary Hospital. They discovered key features of the microbiome and associated metabolic products that appeared only in dogs that entered disease remission. A type of bacteria that produces these compounds, known as secondary bile acids, alleviated disease in a mouse model. And comparing the impact of diet on the dog’s microbiome with that seen during diet therapy in children with Crohn’s, the study team found notable similarities.

“The bacteria in the gut are known to be a really important factor in tipping the scales toward disease,” says Daniel Beiting, senior author on the work and an assistant professor in the School of Veterinary Medicine. “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 begin pursuing this question required treating a population of pet dogs with canine chronic enteropathy (CE), a chronic condition involving weight loss and gut inflammation, diarrhea, occasional vomiting, loss of appetite, and a chronic relapsing and remitting, just as seen in Crohn’s disease. The study involved 53 dogs, 29 with CE being treated at Penn Vet’s Ryan Veterinary Hospital, and 24 healthy controls.

Researchers collected stool samples at the outset of the study and at different times as the sick dogs began a prescription diet to treat their disease. Using advanced genetic sequencing techniques, the team developed a catalog of the microbes present in the stool, a stand-in for the animals’ gut microbiome. They also collected information about the metabolic products present in the stool.

“That gives us a functional read-out of the microbiome,” says Beiting. “It doesn’t just tell us who is there but also what they’re doing.”

Twenty of the 29 sick dogs quickly entered remission. Together, the genomic and metabolite analyses revealed characteristic changes in these dogs. In particular, those that responded well to the diet tended to have an increase in metabolites known as secondary bile acids. These are produced when certain microbes in the gut consume the bile that is released by the liver.

One of these “good” microbes that can give rise to secondary bile acids was the bacterium Clostridium hiranonis, which the researchers found in greater numbers in dogs that went into remission. Dogs that responded well to the diet also had fewer harmful bacteria, such as Escherichia coli and Clostridium perfringens after starting treatment.

To learn more about what these apparent markers of remission were doing, the team took bacteria from the dogs—both when they were sick and after they had entered remission—and grew them in the lab.

“Having these organisms gave us the opportunity to test our hypothesis about what actually causes remission,” says Shuai Wang, a postdoc at Penn Vet and the study’s lead author.

Taking the secondary bile acids found to be associated with remission, the researchers applied them to the E. coli and C. perfringens grown from the sick dogs and found the bile acids inhibited their growth. They also gave C. hiranonis from the dogs to mice with a form of inflammatory bowel disorder to see if the bacteria could reduce disease in a different animal model.

“We observed a stabilization of secondary bile acid levels and reduced inflammation,” Wang says.

“This allowed us to show that secondary bile acids and C. hiranonis aren’t just biomarkers of remission,” says Beiting, “they can actually effect change. Bile acids can block the growth of pathogens, and C. hiranonis can improve gut health in mice.”

As a final step, the researchers looked to a dataset taken from children with Crohn’s disease who were treated with a specialized liquid diet known as exclusive enteral nutrition. Youngsters who responded to the therapy had an increase in numbers of the bacteria species Clostridium scindens, which, like C. hiranonis, is a potent producer of secondary bile acids.

The authors say the findings offer hope for better dietary therapies for IBD, perhaps ones that deliver “good” bacteria such as C. scindens or C. hiranonis while suppressing disease-associated species.

“Similar environmental exposures of dogs and children make the canine IBD model an excellent model of pediatric inflammatory bowel disease,” says Robert N. Baldassano, a study coauthor and pediatric gastroenterologist at Children’s Hospital of Philadelphia. “This study has greatly improved our knowledge of pediatric IBD and will lead to new therapies for children suffering with this disease.”

Source:  Penn Today

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How Humans Have Shaped Dogs’ Brains

Dog brain structure varies across breeds and is correlated with specific behaviors, according to new research published in JNeurosci. These findings show how, by selectively breeding for certain behaviors, humans have shaped the brains of their best friends.

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Over several hundred years, humans have selectively bred dogs to express specific physical and behavioral characteristics. Erin Hecht and colleagues investigated the effects of this selective pressure on brain structure by analyzing magnetic resonance imaging scans of 33 dog breeds. The research team observed wide variation in brain structure that was not simply related to body size or head shape.

The team then examined the areas of the brain with the most variation across breeds. This generated maps of six brain networks, with proposed functions varying from social bonding to movement, that were each associated with at least one behavioral characteristic. The variation in behaviors across breeds was correlated with anatomical variation in the six brain networks.

Studying the neuroanatomical variation in dogs offers a unique opportunity to study the evolutionary relationship between brain structure and behavior.

Read the manuscript in JNeurosci: Significant Neuroanatomical Variation Among Domestic Dog Breeds

Source:  Society for Neuroscience

That spot on Izzy’s muzzle

At a social walk yesterday, quite a few of our friends noticed the purple stitches in Izzy’s muzzle.  She had a lump removed a little over a week ago (her stitches come out on Monday).

Everyone needs to understand that lumps cannot be diagnosed by the naked eye.  Without a biopsy, you can never be sure about the type of cells that are growing there.

In Izzy’s case, the spot on her nose opened up and bled like crazy and, by the following morning, had totally disappeared again.  Bleeding concerns me – hence the reason we went off to the vet.

Izzy's nose

The testing has come back and it’s good news.  The spot was a hemangioma, a benign growth that is related to sun damage.

With the spring and summer on their way, I’ve made a promise to both of us that I will be much more diligent in applying sunscreen to her muzzle each and every day.

Kathleen Crisley, Fear-Free certified professional and specialist in dog massage, rehabilitation and nutrition/food therapy, The Balanced Dog, Christchurch, New Zealand

House­holds feed­ing their dogs and cats with raw food do not con­sider the diet a sig­ni­fic­ant source of in­fec­tions

Raw food research

Raw food denotes any meat, internal organs, bones and cartilage fed to pets uncooked Photo credit: Johanna Anturaniemi

An extensive international survey conducted at the University of Helsinki indicates that pet owners do not consider raw food to considerably increase infection risk in their household. In the survey, targeted at pet owners, raw food was reliably determined to be a contaminant only in three households.

The safety of feeding raw food to pets has become a topic of debate on a range of forums, but so far, no outbreaks of contamination among humans caused by raw pet food have been reported. Raw food denotes any meat, internal organs, bones and cartilage fed to pets uncooked.

Now, a survey conducted at the Faculty of Veterinary Medicine investigated perceptions on food-transmitted pathogens among pet owners who feed their pets raw food.

A total of 16,475 households from 81 countries responded to the survey. Out of these, only 39 households (0.24%) reported having been contaminated by pet food, and were also able to name the pathogen. The most common pathogens reported were Campylobacteria followed by Salmonella, in addition to which there were occurrences of Escherichia coliClostridiumToxoplasmaand a single Yersinia infection.

However, the meat fed to pets had been analysed in only three households (0.02%), identifying the same pathogen as found in the samples taken from the infected individuals. As well as the 39 households above, 24 households (0.15%) reported a contamination from pet food without being able to name the pathogen causing the symptoms.

In total, 99.6% of households feeding their pets raw food did not report any pathogens being transmitted from the raw food to humans. The time the responding households had been feeding raw food to their pets ranged from several weeks to 65 years, with 5.5 years as the mean value. The reported cases of illness covered whole time frame that raw food was consumed in the household.

The median age among the infected individuals was 40.1 years. From among the 39 households with infections, in four the infected individuals were children between two and six years of age, while in two households the infected were immunocompromised individuals (cancer and Crohn’s disease). However, a quarter of these households had children between two and six years of age, while 15% had immunocompromised individuals.

“It was surprising to find that statistical analyses identified fewer infections in the households with more than 50% of the pet diet consisting of raw food. Furthermore, feeding pets raw salmon or turkey was associated with a smaller number of infections,” says researcher Johanna Anturaniemi from the Faculty of Veterinary Medicine.

A positive correlation with infection was only found in relation to children between two and six years of age living in the household, even though most of the infected individuals (90%) were adults.

“This raises the question of whether the pathogens could have been transmitted by children from outdoors, daycare centres or other public spaces, even if pet food had been assumed to be the source of infection,” Anturaniemi says.

According to the researchers, the role of other factors in infections cannot be assessed in more detail within the confines of this study; rather, further research is needed. In contrast, reports of outbreaks of pathogens linked to pet treats and dry food can be found from around the world. In fact, the Dogrisk research group is planning to conduct a comparative follow-up study where infections transmitted from pet food are to be investigated in households that use both raw food and dry food.

The survey was translated into five languages and made available to all dog and cat owners across the globe feeding their cats and dogs raw food.

Ori­ginal art­icle:

Anturaniemi J, Barrouin-Melo SM, Zaldivar-López S, Sinkko H, Hielm-Björkman A. Owners’ perception of acquiring infections through raw pet food: a comprehensive internet-based survey. Vet Rec. 2019 Aug 19. pii: vetrec-2018-105122. doi: 10.1111/vr.105122.

Source:  University of Helsinki Life Science News

The pet effect: FSU researchers find furry friends ease depression, loneliness after spousal loss

As Healthy Aging Month is underway this September, Florida State University researchers have found the companionship of a pet after the loss of a spouse can help reduce feelings of depression and loneliness in older adults.

The study, funded by The Gerontological Society of America and the WALTHAM Centre for Pet Nutrition and published in The Gerontologist, examined depressive symptoms and loneliness among people age 50 and older who experienced the loss of a spouse through death or divorce.

FSU researchers

FSU Researchers Natalie Sachs-Ericsson (L) and Dawn Carr (R). At center is Journey, a golden retriever certified as a pet therapy animal at Tallahassee Memorial Hospital. (FSU Photography Services/Bruce Palmer)

“Increasingly, there’s evidence that our social support networks are really beneficial for maintaining our mental health following stressful events, despite the devastation we experience in later life when we experience major social losses,” said Dawn Carr, lead author and FSU associate professor of sociology. “I was interested in understanding alternatives to human networks for buffering the psychological consequences of spousal loss.”

Carr and her team compared individuals who experienced the loss of a spouse to those who stayed continuously married. Then they explored whether the effects of spousal loss differed for those who had a pet at the time of the death or divorce.

They found all individuals who lost their spouse experienced higher levels of depression. However, people without a pet experienced more significant increases in depressive symptoms and higher loneliness than those who had pets. In fact, those who had a pet and experienced the death or divorce of their spouse were no lonelier than older adults who didn’t experience one of those events.

“That’s an important and impressive finding,” Carr said. “Experiencing some depression after a loss is normal, but we usually are able to adjust over time to these losses. Persistent loneliness, on the other hand, is associated with greater incidents of mortality and faster onset of disability, which means it’s especially bad for your health. Our findings suggest that pets could help individuals avoid the negative consequences of loneliness after a loss.”

Carr’s team used data from a sample of older adults who participated in an experimental survey about human animal interaction as part of the University of Michigan’s Health and Retirement Study in 2012, and linked the data with additional data collected between 2008 and 2014. They identified pet owners as those participants who either had a cat or a dog.

“In everyday life, having a cat or dog may not make you healthier,” Carr said. “But when facing a stressful event, we might lean on a pet for support. You can talk to your dog. They’re not going to tell you you’re a bad person, they’re just going to love you. Or you can pet your cat, and it’s calming.”

The researchers noted that additional studies should be conducted to explain why having pets helps maintain mental health better. However, Carr suggested part of it may relate to whether you feel like you matter to someone.

“Oftentimes, the relationship we have with our spouse is our most intimate, where our sense of self is really embedded in that relationship,” Carr said. “So, losing that sense of purpose and meaning in our lives that comes from that relationship can be really devastating. A pet might help offset some of those feelings. It makes sense to think, ‘Well at least this pet still needs me. I can take care of it. I can love it and it appreciates me.’ That ability to give back and give love is really pretty powerful.”

The findings have potential consequences for social policies. For instance, it may be beneficial to include companion animals in the treatment of people residing in senior-living facilities, or reducing barriers to pet ownership in such settings.

Source:  Florida State University News

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Doggy quote of the month for September

Brigitte Bardot quote

Dogs with lung cancer may get gene-directed treatment with the same drug used to combat a type of human breast cancer

Despite those velvet paintings of poker-playing dogs smoking pipes, cigars and cigarettes, our canine friends really don’t use tobacco. But like many humans who have never smoked, dogs still get lung cancer.photo-for-her2-study

And, like many women who develop a particular type of breast cancer, the same gene — HER2 — also appears to be the cause of lung cancer in many dogs, according to a promising new study of pet dogs led by the Translational Genomics Research Institute (TGen), an affiliate of the City of Hope, and The Ohio State University.

Published in the journal Clinical Cancer Research, this study could have significant implications for people who have never smoked.

TGen and Ohio State found that neratinib — a drug that has successfully been used to battle human breast cancer — might also work for many of the nearly 40,000 dogs in the U.S. that annually develop the most common type of canine lung cancer, known as canine pulmonary adenocarcinoma, or CPAC.

Neratinib inhibits a mutant cancer-causing form of the gene HER2, which is common to both CPAC and HER2-positive human breast cancer patients.

“With colleagues at Ohio State, we found a novel HER2 mutation in nearly half of dogs with CPAC. We now have a candidate therapeutic opportunity for a large proportion of dogs with lung cancer,” said Dr. Will Hendricks, an Assistant Professor in TGen’s Integrated Cancer Genomics Division, Director of Institutional Research Initiatives, and the study’s senior author.

Based on the results from this study, a clinical trial using neratinib is planned for dogs with naturally occurring lung cancer that have the HER2 mutation.

“This is the first precision medicine clinical trial for dogs with lung cancer. That is, the selection of cancer therapy for a particular patient is based on the genomic profile of the patient’s tumor and matched with agents that are known to specially target the identified mutation,” said Dr. Wendy Lorch, an Associate Professor in the Department of Veterinary Clinical Sciences at The Ohio State University College of Veterinary Medicine, who also will run the study’s clinical trial.

“Our team at The Ohio State University has worked for years to find treatments for canine lung cancer. This breakthrough shows the value of these studies for dogs, as well as humans with lung cancer who never smoked,” said Dr. Lorch, who also is the study’s lead author.

CPAC is an aggressive disease that clinically resembles human lung cancer among never-smokers. There is no standard-of-care treatment for CPAC and — prior to the work performed by the TGen-Ohio State team — little was known of the disease’s genetic underpinnings.

“These results are the first example of our efforts to adapt genomics tools from the human world, such as gene sequencing and liquid biopsies, to generate novel insights in canine cancers, with mutual benefit for both,” said Dr. Muhammed Murtaza, Assistant Professor and Co-Director of TGen’s Center for Noninvasive Diagnostics, and one of the study’s contributing authors.

While the sequencing of hundreds of thousands of human cancer genomes has driven the transformational development of precise targeted cancer treatments for humans over the past decade, relatively few canine cancer genomes have undergone similar profiling. The canine cancer genomic discovery and drug development efforts of the TGen-Ohio State team are pieces of a larger puzzle that could similarly transform veterinary oncology, while creating bridges between canine and human cancer drug development.

“This study is groundbreaking because it not only identified a recurring mutation in a canine cancer that had never been found before, but it actually led directly to a clinical trial,” said Dr. Jeff Trent, TGen President and Research Director, and one of the study’s contributing authors. “This clinical translation from dog to human and back is the holy grail of comparative cancer research.”

Lung cancer is the leading cause of cancer death in the U.S., annually taking the lives of more than 154,000 Americans.

“This study is really exciting to us because, not only have we found a recurrent hot-spot mutation in a canine cancer that had never been found before, but it actually has direct clinical translational relevance. For humans, we already have drugs that can inhibit many dysregulated proteins. We hope to show that we can provide the same benefit for dogs with canine cancers,” Dr. Hendricks added.

No dogs were harmed in this study. Only pet dogs with naturally occurring cancer were examined.

This study — Identification of recurrent activating HER2 mutations in primary canine pulmonary adenocarcinoma — lays the foundation for potential rapid translational development. Follow-up clinical and genomic studies have been funded in part by a $300,000 grant investment from the Petco Foundation made possible through their 10-year Pet Cancer Campaign in partnership with Blue Buffalo. Susanne Kogut, President of The Petco Foundation, said her organization’s investment in the next phase of TGen-Ohio State studies is part of a larger effort to improve the health and welfare of pets everywhere.

“We are so excited to be a part of this study of canine lung cancer, which we hope will rapidly benefit our pet, and pet-parent, communities worldwide,” said Kogut, who in 2016 was named one of 25 “women of influence” by Pet Age magazine.

Source:  TGen meda release