Exploring the Microscopic Ecology of the Microbiome

Investigating the microscopic worlds in our dogs may reveal pathways to better health.
By Jane Brackman PhD, July 2015

The microbiome is the invisible world of the hundred trillion bacterial, viral and fungal microbes that live on us and in us—on our hair and skin, behind our ears and inside our eyelids. The bulk of these miniscule microbes are good guys, gut microbiota that congregate in the digestive tract, where they bolster the immune system, manufacture vitamins and digest food to generate nutrients and energy.

Microbial equilibrium is a delicate balancing act, and a broad spectrum of inflammatory and autoimmune diseases is linked to having too many microbes—or too few. For example, researchers know that significantly lower bacterial diversity is found in both people and dogs with chronic inflammatory bowel diseases.

Teasing out the biological interaction of trillions of miniscule microorganisms that colonize the body, and the role they play in well being, is a new frontier. Will it be a watershed moment in veterinary medicine? Scientists are hopeful. The human microbiome has become a hot topic in biologic investigations, and canine research is fast catching up, much of it inspired by the success of the Human Microbiome Project, launched in 2007 by the National Institutes of Health (NIH). Using stool and tissue samples to isolate microorganisms, researchers are mapping the diversity and normal profile of the human microbial community.

Another undertaking, the Human Food Project, invites the public to submit personal and family microbial samples along with samples from family dogs to better understand how a person’s microbiome compares to that of animals living in the same environment. (The project’s dog segment has been discontinued.) The analysis centers on the anthropological co-evolution of humans, animal and plant microbes to understand modern disease against the backdrop of our ancestral/microbial past.

It’s all about dogs at Companion PBx, a new startup that primarily targets the canine digestive tract. Its goal is to build a cumulative gut flora database and develop dietary products customized for dogs’ digestive health. In January 2015, the company launched a Kickstarter campaign to raise money for construction of the database.

According to Companion PBx Chief Science Officer Kelly Scott Swanson, PhD, who’s on the faculty at University of Illinois, Urbana-Champaign’s Department of Animal Sciences, “By sequencing the microbes in your pet’s sample, we obtain a fingerprint of the microbial community in your pet’s GI tract.”

Microbes in Common

Affected by age, environment, ancestry, evolution, genetics and diet, microbial communities vary widely between species and across individuals within a species. A recent study suggests that our housemates—including the family dog—may also affect the composition of our personal microbial signature.

If you and your significant other kiss, hug and/or share a bed with your dog, the three of you have more in common than you think. A study conducted by researchers at the University of Colorado, Boulder, revealed several similarities: Adults who share a dog have more similar mouth microbes than those who don’t. Dog-owning families have more diverse and different microbial colonies than dogless households. Parents tend to share more kinds of mouth bacteria with their dog than they do their children. And children raised with dogs have a wider variety of microbes than dogless kids (Song et al. 2013).

Whether these spit-swapped microbes serve a purpose or are just passing through is not clear. But research shows that children raised with dogs are less likely to be afflicted by eczema (Epstein et al. 2010) and asthma (American Society for Microbiology 2012).

The notion that microorganisms in the canine gastrointestinal tract might have unique properties is not new. Early Romans understood the medical value of a well-run therapy dog program. Health temples, the ancient equivalent of modern-day outpatient clinics, were staffed with live-in cynotherapists, gentle dogs who wandered about the grounds greeting patients and licking wounds. Were the dogs healing only psychosomatic injuries? Time and additional research funding will tell.

The idea that our microorganisms may to some extent be collectively beneficial is intriguing. People and dogs have been exchanging microbes for at least 30,000 years, since the first little cave girl kissed the first proto-dog puppy smack on the muzzle. That’s a long history of sharing. It’s possible that our microorganisms are at least symbiotic, and perhaps even played a role in the dramatic domestication of the dog.

Theoretically, many thousands of years ago, a population of carnivorous wolves or ancient proto-dogs (depending on where you stand in the dog-domestication debate) transitioned from a meat-heavy diet to one laden with grain, a consequence of the agrarian revolution.

Scientists know that the acquisition of a new diet is a fundamental driver for the evolution of a new species (Dale, Moran 2006). When species transition from carnivorous to omnivorous diets, the gut microbial community co-diversifies with the host and drives further evolution (Ley et al. 2008). As human diets changed, so too did those of Canis familiaris. Over time, as we incorporated these unique animals into our daily lives, we continued to reshape them.

Challenges

In humans, autoimmune and inflammatory diseases are on the increase. Scientists can’t verify a similar pattern in dogs because epidemiological studies are rarely conducted in veterinary medicine. Additionally, many autoimmune conditions are diagnosed based on the patient’s subjective description of symptoms.

But this is not the case with itchy skin. Dogs who scratch themselves incessantly are highly likely to have allergies. When researchers compared microbial colonies on the skin of healthy dogs to those of dogs with allergies, they found that non-allergic dogs have much richer and diverse skin microbial communities (Hoffmann et al. 2014).

But when it comes to proving causality, scientists wisely err on the side of caution. It’s not understood if a change in the microbiome causes certain conditions, or if it occurs as a consequence of the conditions. Nor is it absolutely clear that more diversity is better than less. At this point, scientists cannot say with confidence exactly what a healthy microbiome should look like in the dog.

Moreover, what seems logical may not be so. For instance, anyone who has lived with a poop-eating pooch has wondered why some dogs do and other don’t. Are coprophagic dogs seeking microbes lacking in their gut? Surprisingly, research involving mice suggests that this might not be the case; coprophagia in germfree mice is the same as in conventional lab mice (Ebino et al. 1987).

Other questions arise: Are the microbiomes of individual dog breeds more similar to each other than they are to those of other breeds? And could these isolated microbial communities drive breed-specific ailments?

Jan Suchodolski, DVM, a Texas A&M veterinary medical and biomedical sciences researcher who studies dog and cat gastrointestinal diseases, says that this doesn’t seem to be the case. As he noted, “So far, we do not have any clear evidence that gut microbiomes are more similar within breeds. Environmental influences such as age, diets and antibiotics, and especially the effects of GI disease, are larger than any breed effect.

“It may be possible that we missed an effect, as we have not evaluated thousands of animals. But if there were a breed effect, it would probably be very minor. Even within puppies of the same litter, the microbiome shows huge inter-animal variation, so the animal effect is much stronger than any other effect.”

Idiopathic canine inflammatory bowel disease (IBD) is a gastrointestinal condition in which the digestive tract is chronically inflamed. Symptoms include vomiting, diarrhea and weight loss. Dogs with IBD have significantly lower bacterial diversity as well as microbial communities that are distinct from those of healthy dogs. In 2014, Dr. Suchodolski and his colleagues conducted a study of 22 companion dogs, half of whom suffered from idiopathic IBD (Minamoto et al. 2015). They wanted to know if traditional treatments—steroids and special diets—directly or indirectly created a more robust microbial community.

After treatment, the sick dogs felt a lot better. However, there was no change in their gut microbiota. The researchers concluded, “This study demonstrates intestinal dysbiosis [microbial imbalance] and altered serum metabolite profiles in dogs with IBD. But medical therapy doesn't seem to affect the intestinal dysbiosis.”

It could be that, rather than triggering the condition, microorganisms are compromised by it. Researchers also suspect that biological environmental stresses are involved in ways not yet understood. Dr. Suchodolski added, “It may be that we need longer follow-up periods of treatments to see potential improvements. Another reasonable theory is that with the current standard therapies—for instance, immunosuppression—we just control clinical signs, but the underlying etiology of the disease is ongoing.”

Culprits

When it comes to treating dogs for myriad problems, vets often prescribe antibiotics, and for good reason: antibiotics save lives. But the war on infection sometimes puts good bacteria in the line of fire, too. When assaulted by repeated antibiotic use, some classes of gut bacteria struggle to recover. If the affected bacteria play a pivotal role in autoimmune health, overuse of antibiotics may coincide with a decrease in healthy autoimmune responses.

Antibiotics are not the only culprits. Scientists suspect that in human births, Cesarean deliveries may contribute to an increase in autoimmune weaknesses as well. In a vaginal birth, the fetus departs the womb without a single microbe but acquires them by passing through the mother’s birth canal. By the time the newborn takes his first breath, he is covered with colonies of bacteria that kick-start his immune system, establish a healthy digestive tract, help shape his growing brain and even protect him from psychiatric disorders. C-section babies start life without the microbes they would have picked up from vaginal delivery, suggesting that the colonization of the newborn might be delayed (Jakobsson et al. 2014).

Medical disorders connected to non-vaginal delivery and the slow introduction of protective bacteria have not been studied in the dog. Considering that a number of breeds with exceptionally flat, wide skulls—such as the Boston Terrier, French Bulldog and Bulldog—must have their pups delivered via C-section, it’s an area that deserves further study.

Or is diet the problem? Commercially manufactured dog chow was introduced in the U.S. in the mid-1920s. By the 1950s, processed dog food like Friskies, Sergeant’s and Purina were widely available through local grocery stores. Today in the U.S., we spend more than $10 billion a year on commercial pet food. The question arises: has the increase in autoimmune diseases paralleled the rise in popularity of processed dog food?

Because veterinary practices typically don’t collect this type of empirical data, the answer is, at best, a guess. But many dog owners think so, and have eliminated or cut back on processed foods in favor of raw meat and vegetables. However, as of now, there is no definitive evidence to show that fresh foods modulate the gut microbiota.

Cures

Sophisticated DNA sequencing technology has opened up the invisible world to scientific scrutiny. But determining its impact on the host species is difficult and time-consuming. Researchers need to locate and identify a microbe’s fingerprint, then remove a sample and grow it in a culture, a process especially difficult with shyer microbes that are destroyed by oxygen or stomach acid.

To figure out why we get sick and the role microbes play in illness, researchers must first determine how these trillions of organisms interact with each other. And the fact that scientists can prove a problem exists doesn’t mean they know how to fix it.

Developing therapeutic dog foods that target specific vulnerabilities may help, but will take time to develop. Although the probiotic movement may oversell their benefits, probiotics (friendly bacteria like those that live in the gut) are effective in some cases. And prebiotics, foods that encourage growth of good bacteria already present, may help as well.

The University of Pennsylvania School of Veterinary Medicine (Penn Vet) is recruiting dogs with acute symptoms of diarrhea and/or vomiting for a new clinical trail that will evaluate the role of the intestinal microbiome—the community of “good” bacteria that live in the gut—on chronic gastrointestinal diseases. Therapy will include simple diet change, treatment with antibiotics or combination therapy with steroids for more complicated cases.

Penn Vet researchers anticipate that their study may reveal how gut microbiota influence and respond to treatment, which in turn could lay the groundwork for future projects using treatments such as prebiotics, probiotics or fecal transplants (transferring “good” microorganisms from a donor’s healthy stool to the patient’s gastrointestinal tract). According to Research Assistant Professor Dr. Daniel Beiting, “Whereas past studies have used a single method to sequence bacterial DNA, the Penn Vet study will use a more sophisticated approach called metagenomics, generating a much more comprehensive catalog of bacteria in the stool and providing insight into what they might be doing.”

Penn Vet is currently looking for dogs with chronic gastrointestinal problems. People interested in enrolling their dog in the study—Evaluating the Role of the Microbiome in the Resolution of Canine Chronic Enteropathy—should email Penn Vet’s Veterinary Clinical Investigations Center at vcic@vet.upenn.edu, or call (215) 573-0302.

Future possibilities are exciting. In the meantime, kiss your dog. It’s good for you in more ways than one.

Jane Brackman, PhD, is an authority on the cultural history of canine domestication and the author of two books on pets in 19th-century America. See her new pup, Barkley, and watch him grow on her blog.

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