Emily R Murray1,2, Mylon Kemp2, Tanya T Nguyen2,3,4. 1. Division of Biological Sciences, University of California at San Diego, La Jolla, CA, USA. 2. Department of Psychiatry, University of California at San Diego, La Jolla, CA, USA. 3. Sam and Rose Stein Institute for Research on Aging, University of California at San Diego, La Jolla, CA, USA. 4. VA San Diego Healthcare System, San Diego, CA, USA.
Abstract
OBJECTIVE: The gut microbiome is a complex community of microorganisms that inhabit the gastrointestinal tract. The microbiota-gut-brain axis encompasses a bidirectional communication system that allows the gut to influence the brain via neural, endocrine, immune, and metabolic signaling. Differences in the gut microbiome have been associated with psychiatric and neurological disorders, including Alzheimer's Disease (ad). Understanding these ad-associated alterations may offer novel insight into the pathology and treatment of ad. METHOD: We conducted a narrative review of clinical studies investigating the gut microbiome in ad, organizing the results by phyla to understand the biological contributions of the gut microbial community to ad pathology and clinical features. We also reviewed randomized clinical trials of interventions targeting the microbiome to ameliorate ad symptoms and biomarkers. RESULTS: Alpha diversity is reduced in patients with ad. Within Firmicutes, taxa that produce beneficial metabolites are reduced in ad, including Clostridiaceae, Lachnospiraceae, Ruminococcus, and Eubacterium. Within Bacteroidetes, findings were mixed, with studies showing either reduced or increased abundance of Bacteroides in mild cognitive impairment or ad patients. Proteobacteria that produce toxins tend to be increased in ad patients, including Escherichia/Shigella. A Mediterranean-ketogenic dietary intervention significantly increased beneficial short-chain fatty acids and taxa that were inversely correlated with changes in ad pathological markers. Probiotic supplementation with Lactobacillus spp. and Bifidobacterium spp. improved cognitive function and reduced inflammatory and metabolic markers in patients with ad. CONCLUSIONS: The gut microbiome may provide insight into ad pathology and be a novel target for intervention. Potential therapeutics include probiotics and dietary intervention.
OBJECTIVE: The gut microbiome is a complex community of microorganisms that inhabit the gastrointestinal tract. The microbiota-gut-brain axis encompasses a bidirectional communication system that allows the gut to influence the brain via neural, endocrine, immune, and metabolic signaling. Differences in the gut microbiome have been associated with psychiatric and neurological disorders, including Alzheimer's Disease (ad). Understanding these ad-associated alterations may offer novel insight into the pathology and treatment of ad. METHOD: We conducted a narrative review of clinical studies investigating the gut microbiome in ad, organizing the results by phyla to understand the biological contributions of the gut microbial community to ad pathology and clinical features. We also reviewed randomized clinical trials of interventions targeting the microbiome to ameliorate ad symptoms and biomarkers. RESULTS: Alpha diversity is reduced in patients with ad. Within Firmicutes, taxa that produce beneficial metabolites are reduced in ad, including Clostridiaceae, Lachnospiraceae, Ruminococcus, and Eubacterium. Within Bacteroidetes, findings were mixed, with studies showing either reduced or increased abundance of Bacteroides in mild cognitive impairment or ad patients. Proteobacteria that produce toxins tend to be increased in ad patients, including Escherichia/Shigella. A Mediterranean-ketogenic dietary intervention significantly increased beneficial short-chain fatty acids and taxa that were inversely correlated with changes in ad pathological markers. Probiotic supplementation with Lactobacillus spp. and Bifidobacterium spp. improved cognitive function and reduced inflammatory and metabolic markers in patients with ad. CONCLUSIONS: The gut microbiome may provide insight into ad pathology and be a novel target for intervention. Potential therapeutics include probiotics and dietary intervention.
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