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Oral Microbiome Imbalances Could Provide Early Warning of Disease
Image caption: Fragments of amyloid precursor protein aggregate in β-amyloid plaques, seen here in dark brown. These plaques have been found in the brains of patients with Alzheimer’s disease. Credit: Wikimedia Commons.
By Daniel Erenstein, Neurobiology, Physiology & Behavior ‘21
Author’s Note: I first learned about research on the oral microbiome while covering this year’s annual meeting of the American Association for the Advancement of Science in February. Under the theme of “Understanding Dynamic Ecosystems,” the conference, which was held virtually, welcomed scientists, journalists, students, and science enthusiasts for four days of sessions, workshops, and other talks. The human microbiome, home to trillions of bacteria and other microbes, is as dynamic an ecosystem as they come. This article focuses on the bacteria that live in our mouths and their fascinating role in diseases such as diabetes and chronic kidney disease. With this article, I hope that readers consider further reading on the diverse, lively ecosystems within our bodies. For more stories on the microbiome, The Aggie Transcript is a great place to start.
There is more to the oral microbiome than meets the mouth. Established within a few minutes of birth, this diverse community of bacteria, fungi, and other microbes lives on every surface of our mouths throughout our lives [1]. For decades, scientists have researched these microorganisms and their role in dental diseases.
But far less is known about the interactions of these bacteria and their products with other parts of the body, and these interactions could hold a particularly important role in human health.
“We’ve always thought of the mouth as somehow in isolation, that oral health does not somehow impact the rest of the body,” said Purnima Kumar, DDS, MS, PhD, professor of periodontology at Ohio State University, during a session at the American Association for the Advancement of Science annual meeting that took place on February 8 [2].
Scientists, though, are increasingly looking to the oral microbiome for answers to questions about health and disease [3].
“The time is absolutely right for us to start putting the mouth back into the body,” Kumar said during the session “Killer Smile: The Link Between the Oral Microbiome and Systemic Disease.”
Panelists highlighted three systemic diseases — diabetes mellitus, rheumatoid arthritis, and Alzheimer’s disease — and their unexpected connection to disturbances in the oral microbiome [4-6]. A common thread running through all three diseases is an association with periodontitis, a gum disease triggered by the accumulation of bacteria, viruses, and even fungi in dental biofilm, or plaque, on the surface of teeth [7].
In health, there is peace between oral microbes and our immune system. Healthy and frequent communication — molecular diplomacy between bacteria and immune surveillance — maintains stable relations. But microbial imbalances due to bacterial buildup in plaque can cause inflammatory immune reactions, resulting in the gradual breakdown of the barrier between biofilm and gum tissue.
“When you have gum disease, that crosstalk, that communication, that harmony is broken down,” Kumar said.
When bacteria subsequently invade our gum tissues, there are consequences for human disease [8].
Mark Ryder, DMD, professor of periodontology at University of California, San Francisco, studies the role of one such bacterium, Porphyromonas gingivalis, in disease [9]. This bacterium secretes enzymes called gingipains, which are essential for its survival.
In the case of Alzheimer’s disease, these gingipains can travel through the bloodstream, cross the blood-brain barrier, and accumulate in brain regions like the hippocampus, which is involved in memory. There, they help break down an embedded membrane protein called amyloid precursor protein into fragments, which group together in deposits found in people with Alzheimer’s disease.
Further study of gingipains and other microbial products could provide insight into a “critical early event in the initiation and progression of Alzheimer’s disease,” Ryder said.
Similarly, rheumatoid arthritis can be triggered by immune responses to other by-products of P. gingivalis, including protein antibodies that cause joint inflammation, according to Iain Chapple, BDS, PhD, professor of periodontology at the University of Birmingham [5].
Past research on links between the oral microbiome and systemic disease has even shown that these effects can travel a two-way street.
This is apparent in the research of Dana Graves, DDS, DMSc, professor of periodontics at University of Pennsylvania, whose work has examined the effects of diabetes on our microbiome, and vice versa [4].
“Diabetes impacts the mouth in a very profound way,” said Graves, adding that the inflammatory responses to bacteria caused by diabetes lead to disruption of the microbiome.
“This bidirectionality is something we saw first with diabetes, we’ve seen it now with rheumatoid arthritis, and it appears now that we’re starting to see it with chronic kidney disease,” Chapple said. “We need to start really digging down into [biological mechanisms] to understand more about that relationship.”
However, the verdict is still out on how much bacterial products such as gingipains contribute to disease. For Ryder and others, the existing data is insufficient — fully answering that question depends on carefully constructed clinical trials.
“When we’re trying to establish a link between something like the microbiome and the mouth and Alzheimer’s, association studies are important, the actual underlying biological mechanisms are important, but finally what sort of seals the deal, of course, is the actual effects of intervention,” Ryder said.
An ongoing clinical trial with more than 600 patients is evaluating the success of gingipain inhibitors in preventing symptoms of Alzheimer’s disease [10]. The results, expected by the end of this year, could carry implications not just for the treatment of Alzheimer’s disease but any disease with underlying roots in the oral microbiome.
Regardless of the results, it’s clear that breaking out the toothbrush and floss every day is crucial to our overall well-being.
References:
- Ursell LK, Metcalf JL, Parfrey LW, Knight R. 2012. Defining the human microbiome. Nutr Rev. 70 Suppl 1: S38-S44. https://doi.org/10.1111/j.1753-4887.2012.00493.x.
- Kumar P, D’Souza R, Shaddox L, Burne RA, Ebersole J, Graves D, Ryder MI, Chapple I. 2021. Killer Smile: The Link Between the Oral Microbiome and Systemic Disease [Conference presentation]. AAAS Annual Meeting [held virtually]. https://aaas.confex.com/aaas/2021/meetingapp.cgi/Session/27521.
- Deo PN, Deshmukh R. 2019. Oral microbiome: Unveiling the fundamentals. J Oral Maxillofac Pathol. 23(1): 122-128. doi:10.4103/jomfp.JOMFP_304_18.
- Graves DT, Ding Z, Yang Y. 2020. The impact of diabetes on periodontal diseases. Periodontol 2000. 82(1): 214-224. https://doi.org/10.1111/prd.12318.
- Lopez-Oliva I, Paropkari AD, Saraswat S, Serban S, Yonel Z, Sharma P, de Pablo P, Raza K, Filer A, Chapple I, et al. 2018. Dysbiotic subgingival microbial communities in periodontally healthy patients with rheumatoid arthritis. Arthritis Rheumatol. 70(7): 1008-1013. https://doi.org/10.1002/art.40485.
- Dioguardi M, Crincoli V, Laino L, Alovisi M, Sovereto D, Mastrangelo F, Lo Russo L, Lo Muzio L. 2020. The Role of Periodontitis and Periodontal Bacteria in the Onset and Progression of Alzheimer’s Disease: A Systematic Review. J Clin Med. 9(2): 495. https://doi.org/10.3390/jcm9020495.
- Arigbede AO, Babatope BO, Bamidele MK. 2012. Periodontitis and systemic diseases: A literature review. J Indian Soc Periodontol. 16(4): 487-491. https://doi.org/10.4103/0972-124X.106878.
- Curtis MA, Diaz PI, Van Dyke TE. 2020. The role of the microbiota in periodontal disease. Periodontol 2000. 83(1): 14-25. https://doi.org/10.1111/prd.12296.
- Ryder MI. 2020. Porphyromonas gingivalis and Alzheimer disease: Recent findings and potential therapies. J Periodontol. 91 Suppl 1: S45-S49. https://doi.org/10.1002/JPER.20-0104.
- Cortexyme Inc. 2021. GAIN Trial: Phase 2/3 Study of COR388 in Subjects With Alzheimer’s Disease. ClinicalTrials.Gov. Identifier NCT03823404. https://clinicaltrials.gov/ct2/show/NCT03823404.
The Similarity of Human’s Microbiomes with Dogs
By Mangurleen Kaur, Biological Science, 23’
Author’s Note: In one of my classes of basic biology, I got to learn about microbes. That class discussed some relationships between microbes and between human beings. One of the points that stuck in my mind was the relationship of microbes between humans and one of our favorite pets, dogs. By researching this topic, I found it so astounding that I decided to write about it. I hope this piece will be interesting not only for science-lovers but also for the general public.
Both, inside and out, our bodies harbor a huge array of microorganisms. These microorganisms are a diverse group of generally minute life forms, which are called microbiota when they are found within a specific environment. Microbiota can refer to all the microorganisms found in an environment including bacteria, viruses, archaea, protozoa, and fungi. Furthermore, the collection of genomes from all the microorganisms found in a particular environment is referred to as a microbiome. According to the Human Microbiome Project (HMP), this plethora of microbes contribute more genes responsible for human survival than humans contribute. Researchers also estimated that the human microbiome consisted of 360 times more bacterial genes than human genes. Their results show that this contribution by microbes is critical for human survival. For instance, in the gastrointestinal tract bacterial genes are present, which allow humans to digest and absorb nutrients that otherwise would be unavailable. In addition to this, microbes also assist in the synthesis of many beneficial compounds, like vitamins and anti-inflammatory agents which our genome cannot produce. (4)
Where does this mini-ecosystem start from? The microbiome comes in our body as soon as we come out from the mother’s womb, we acquire them from the mother’s vagina and then, later on, by breastfeeding which plays a great role in making the microbes’ own unique community. There are several factors that influence the microbiome which include physiology, food, lifestyle, age, and environment. These are not only present in humans, but also in most animals and play a significant role in their health. For instance, gastrointestinal microorganisms exist in symbiotic associations with animals. Microorganisms in the gut assist in the digestion of feedstuffs, help protect the animal from infections, and some microbes even synthesize and provide essential nutrients to their animal host. This gives us an idea of how important these microorganisms are to our living system as a whole.(3)
Besides the human’s strong emotional connection with the dogs, there is also a biological relationship between the human and dog’s interactions. In context of this interesting relationship, research has been conducted. Computational biologist Luis Pedro Coelho and his colleagues at the European Molecular Biology Laboratory, in collaboration with Nestlé Research, studied the gut microbiome (the genetic material belonging to the microbiota) of beagles and retrievers. They found that the gene content of the dog’s microbiome showed more similarities to the human gut microbiome than to the microbiomes of pig or mice. When researchers mapped the gene content of the dog, mouse and pig microbiome in contrast to the human gut genes, they found that respectively 63%, 20% and 33% overlapped.(5) This shows the extensive similarities between human and dog’s gut microbiomes in comparison to other animals. Speaking on the discovery, Luis Pedro Coelho says: “We found many similarities between the gene content of the human and dog gut microbiome. The results of this comparison suggest that we are more similar to man’s best friend than we originally thought.” (1)
The University of Colorado Boulder did a study on the types of microbes present on the different parts of humans, to better understand the diversity and its significance for the human’s body. They conducted the study on 60 American families in which they sampled 159 people and 36 dogs. The team took samples from tongue, forehead, right and left palm and fecal samples to detect individual microbial communities. Through research, the researcher learned that people who own dogs are much more likely to share the same kinds of these “good” bacteria with their dogs. They have also learned that children who are raised with dogs are less likely than others to develop a range of immune-related disorders, including asthma and allergies. “One of the biggest surprises was that we could detect such a strong connection between their owners and pets,” said Knight, a faculty member at CU-Boulder’s BioFrontiers Institute.(6) The results found that adults who have a dog and they live together, share the greatest number of skin phylotypes while adults who neither have a dog nor live together share the least.
The University of Arizona is also conducting another research study, with some other universities including UC San Diego, in which they are seeking healthy people from Arizona age 50 or older, who have not lived with dogs for at least the past 6 months. Then they are selecting persons who would like to live with the assigned dogs. The goal of the study is to see whether the dogs enhance the health of older people and work as probiotics (good bacteria). But this research is ongoing and the outcomes are not yet released. Rob Knight, Professor of Pediatrics and Computer Science & Engineering at UC San Diego and his lab studied microbiomes. Knight and his team found that the microbial community on adult skin are on average more similar to those of their own dogs than to others. They also found that cohabiting couples share more microbes with one another if they have a dog, compared with couples who don’t have a dog. Their research suggests that a dog’s owner can be identified just by analyzing the microbial diversity of the dog and its human, as they share microbiomes. These studies are finding a critical relationship that is very helpful in microbiology and the overall health field in science. (2)
These studies reveal the various interesting relationships of microbiomes with us and other living beings. So far, the studies discussed how dog’s microbiomes are shared by the owner and how gene sequencing helps us to understand these connections. The growing understanding of this connection with microorganisms raises many other outstanding questions like what are the health benefits of a dog to a human? How can they help in preventing certain chronic diseases? This represents an exciting challenge for scientists and researchers to refine their understanding of microbiomes and find answers to these further emerging questions.
Work Cited
- “NIH Human Microbiome project defines normal bacterial makeup of the body”. National Institutes of Health, U.S. Department of Health and Human Services. www.nih.gov. Published on August 31, 2015. Acessed May 10, 2020
- Ganguly, Prabarna. “Microbes in us and their role in human health and disease”. www.Genome.gov. Published on May 29, 2019. Accessed May 10, 2020.
- “Dog microbiomes closer to humans’ than expected”. Research in Germany, Federal Ministry of Education and Research. www.researchingermany.org. Published on April 20, 2018. Accessed May 11, 2020.
- Trevino, Julissa. “A Surprising Way Dogs Are Similar to Humans.” www. Smithsonianmag.com. Published on April 23, 2018. Accessed February 11, 2020.
- Song, Se Jin, Christian Lauber, Elizabeth K Costello, Catherine A Lozupone, Gregory Humphrey, Donna Berg-Lyons, Gregory Caporaso, et al. “Cohabiting Family Members Share Microbiota with One Another and with Their Dogs.” eLife. eLife Sciences Publications, Ltd. elifesciences.org. Published on April 16, 2013. Accessed May 11, 2020.
- Sriskantharajah, Srimathy. “Ever feel in your gut that you and your dog have more in common than you realized?” www.biomedcentral.com. Published on April 11, 2018. Accessed February 11, 2020.
“Gut Feeling”: How Does Modulation of Gut Microbiome Affect Depression Pathophysiology and Status?
By Raida Aldosari, Nutrition Science (Biology option) ’18
Author’s Note: I wrote this literature review as part of my UWP 104F class with Dr. Lisa Sperber. The assignment was to choose a clinically-relevant topic, review the existing body of literature on this topic, and choose a specific area to write on. My topic of interest was about the relationship between gut microbiome and the brain. I became interested in this topic after reading an article about the differences between the microbial composition of individuals with depression. By the end of the quarter, my research question evolved from “how does our diet affect our brain or mood?” to “how does modulation of gut microbiome affect depression pathophysiology?” I enjoyed the flexibility of the assignment, and I greatly benefited from the guidance provided by Dr. Sperber. I would recommend this class to anyone interested in health-related fields, especially in research!
The Infant Airway Microbiome Linked to Childhood Asthma
By Shivani Kamal, Biochemistry and Molecular Biology, ’17
Author’s Note:
“I am pursing a career in pediatrics and wanted to familiarize myself with new research regarding health and development of children. I was amazed at the advancements of medical technology which allow us to understand diseases and create potential cures, previously never thought possible. My purpose for writing this review is to show scientific audiences the most current research on how bacteria in the respiratory microbiome has an impact on asthma. Recently, much research initiated by the Human Microbiome Projects (HMP) proved that the bacteria living on and inside humans contribute to the health and disease of the body. This review is meant to educate scientists on the most recent information on development of childhood asthma and prompt others to conduct future research on preventative treatments for the disease.”
The hunter-gatherer gut microbiome
By: Jenny Cade, Biochemistry and Molecular Biology ‘15
In a paper published in Nature Communications on April 15, researchers profiled the gut microbiota of a group of hunter-gatherers in Tanzania known as the Hadza. They compared the results to those of people living in Italy, and found that the two groups have very different species composition. The Hadza don’t only have different kinds of gut microbes than Westerners, but a more diverse collection of microbes as well. The researchers say that this is most likely due to the dramatic difference between hunter-gatherer and Western diets.