As of 2019, approximately 5.8 million Americans were diagnosed with Alzheimer’s. Alzheimer’s is characterized by progressively worsening cognitive conditions, with symptoms widely ranging to include mental decline, confusion, and delusions. In addition to the cognitive symptoms, patients also experience various behavioral and psychological symptoms, largely impacting one’s quality of life. Despite these devitalizing symptoms, there continues to be no cure for Alzheimer’s, with only drugs and targeted therapies to alleviate the symptoms. Unfortunately, Alzheimer’s is not the only disease without a cure. Food allergies continue to affect 32 million Americans, and the condition presents with no known cause or definitive cure. Due to their complex natures, Alzheimer’s and food allergies have been at the forefront of medicinal research. However, two researchers recently discovered a similar treatment for both conditions. Dr. Sam Sisodia from the University of Chicago and Dr. Lynn Bry at the Brigham and Women's Hospital and Boston Children's Hospital created distinct research protocols that identified the gut microbiome as a possible treatment option for Alzheimer’s and food allergies. Through their research, both Dr. Sisodia and Dr. Bry studied the gut microbiome and discovered its distinct connection to both Alzheimer’s and food allergies, respectively.
Dr. Bry recognized the dramatic impact food allergies had on patients’ life. To avoid allergic reactions, many patients simply avoid problematic foods, but this often leads to instances of malnutrition and electrolyte imbalances. Past research studies have indicated that the gut microbiome plays a vital role in the development and reversal of food allergies. Thus, Dr. Bry investigated the gut microbiome as a possible treatment option for the condition. The research team conducted the study in both human and mice models as a means to understand the primary bacterial species involved in food allergies, and conducted the study in two phases. In the first phase, the team periodically collected fecal samples from 56 infants who had food allergies and 98 infants who were not diagnosed with food allergies. The fecal samples were then transplanted into mice, and all the mice in the study were sensitized to eggs. The results indicated that the mice that received the non-allergy fecal transplants were protected against the egg sensitivity, as compared to those mice that received the allergy fecal transplants. The first phase of the study allowed the team to isolate a specific group of bacteria that protected against food allergies. To gain further specificity, the team continued with phase two. Using computational approaches, the team investigated bacteria in a healthy human microbiome, specifically ones that protected against allergies. Following the analyses, the team then identified five to six species of protective microbes in the human microbiome, and orally administered these microbes into the mice. The five to six microbe species belonged to the Clostridiales and the Bacteroidetes classes and were found to adequately protect the mice against the allergy. Thus, through Dr. Bry’s study, the team concluded that an oral formula of five to six species of bacteria found in the human gut microbiome inhibited the development of food allergies and also reversed the condition. Ultimately, Dr. Bry successfully identified the role of the human gut microbiome in patients with food allergies, allowing for the development of targeted treatment methods.
Interestingly, Dr. Sisodia conducted a separately distinct research study concerning Alzheimer’s, yet also identified the human gut microbiome as a target to treat Alzheimer’s. Dr. Sisodia first determined that the Aβ plaques were the principal components of the vascular and parenchymal amyloid in Alzheimer’s disease. At the same time, emerging evidence suggested that gut microbial diversity can regulate brain function. Thus, Dr. Sisodia hypothesized that the composition of the intestinal microbiome might play a role in modulating neuroinflammation that ultimately influenced AB plaque deposits and further Alzheimer’s disease. To execute his protocol, Dr. Sisodia treated APPSWE /PSI∆E9 mice throughout their lifespans. At two weeks old, the mice were treated daily with a high dose combination of antibiotics. The solution contained Kanamycin, Gentamicin, Colistin, Metronidazole, and Vancomycin. The mice were treated for one week with the antibiotic solution, after which they were given drinking water with a low-dose antibiotic solution for the rest of their lifespan. The results indicated that the bacterial abundance remained unchanged in antibiotic-treated APPSWE /PSI∆E9 mice. However, Dr. Sisodia noted that the Aβ plaque deposits decreased by 40-50%, thus indicating the effect of the gut microbiome on the Aβ plaques. Furthermore, the results did present with a caveat as these findings were only visualized in male mice and not female mice. Nonetheless, Dr. Sisodia connected the gut microbiome to demonstrate its role in reducing Aβ plaque, thus furthering the research in developing a curative treatment for Alzheimer’s.
To this day, Alzheimer’s and food allergies continue to be severe conditions. The mystery of these conditions translates to a degree of uncertainty, thus further exacerbating patients’ discomfort. However, the research for both Alzheimer’s and food allergies is growing at an unprecedented rate, allowing for the emergence of several therapies and drugs. Both Dr. Sisodia and Dr. Bry identified the human gut microbiome in treating both Alzheimer’s and food allergies. Their work created the foundation for future research studies, as well as treatment plans and targeted drug therapies. For example, from her findings, Dr. Bry and her team are currently working on a live human bio-therapeutic product to prevent, treat, and reverse food allergies. Furthermore, due to the extreme versatility and applicability of the gut microbiome, it has become a topic of interest to investigators. Several studies have identified the gut microbiome as being related to PTSD, Crohn’s disease, and Parkinson’s, thus allowing for treatments for many other conditions. Although the gut microbiome provides hope for patients globally, the unpredictability surrounding the gut microbiome continues to be a barrier in the development of new treatments. However, both Dr. Sisodia’s and Dr. Bry’s work are progressing the field in the right direction. Ultimately, the gut microbiome will continue to emerge as vital in the progression of the medical field.
References
Azza Abdel-Gadir, Emmanuel Stephen-Victor, Georg K. Gerber, Magali Noval Rivas, Sen Wang, Hani Harb, Leighanne Wang, Ning Li, Elena Crestani, Sara Spielman, William Secor, Heather Biehl, Nicholas Dibendetto, Xiaoxi Dong, Dale T. Umetsu, Lynn Bry, Rima Rachid, Talal A. Chatila. Microbiota therapy acts via a regulatory T cell MyD88/RORγt pathway to suppress food allergy. Nature Medicine, 2019; DOI: 10.1038/s41591-019-0461-z
Dodiya, H. B., Kuntz, T., Shaik, S. M., Baufeld, C., Leibowitz, J., Zhang, X., ... & Sisodia, S. S. (2019). Sex-specific effects of microbiome perturbations on cerebral Aβ amyloidosis and microglia phenotypes. Journal of Experimental Medicine, 216(7), 1542-1560.
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