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Alzheimer’s Disease, the Microbiome, and 21st Century Medicine
Published in David Perlmutter, The Microbiome and the Brain, 2019
Comparison of the microbiomes of patients with dementia due to Alzheimer’s disease versus age-matched controls showed a marked difference in both the complexity and distribution of microbiota, as shown by Vogt et al. (Vogt et al., 2017) and noted in this book’s chapter by Dr. Zhang. The phyla Firmicutes and Actinobacteria were reduced in patients with Alzheimer’s disease, a finding that parallels results from patients with obesity and type 2 diabetes. Within Firmicutes, the families Ruminococcaceae, Turicibacteraceae, Peptostreptococcaceae, Clostridiaceae, and Mogibacteriaceae were reduced, and within Actinobacteria, the family Bifidobacteriaceae was reduced. In contrast, members of the phylum Bacteroidetes were found to be increased in patients with Alzheimer’s disease, reflected at the family level by an increase in Bacteroidaceae and Rikenellaceae. This reduction led the authors to speculate that the insulin resistance associated with all three conditions (Alzheimer’s, obesity, and type 2 diabetes) may actually be a microbiome-driven mechanism. Furthermore, the degree of abnormality in the cerebrospinal fluid (CSF) samples from Alzheimer’s patients tended to correlate with the microbiome alterations, such that those individuals with more exaggerated microbiome changes tended to also have more severe CSF abnormalities.
The Role of Gut Microbiota in the Pathogenesis and Treatment of Diabetes
Published in Emmanuel C. Opara, Sam Dagogo-Jack, Nutrition and Diabetes, 2019
Stephen J. Walker, Shaun P. Deveshwar
Based on the results of the NOD mice study, the Idd3 and IddI5 alleles were studied to see how manipulation of the IL-2 pathway might impact DM-1 susceptibility in humans. This was done using human samples from a cohort twin study, conducted in the United Kingdom, which recruited 1,392 individuals. The twin study previously looked at the stool microbiome and single nucleotide polymorphism (SNP) genotyping of all enrolled subjects. Using these data from the twin study, this research team looked for associations between SNPs and IL-2 pathway interactions and Treg functioning. They calculated a combined risk score, and the analysis suggested a DM-1 susceptibility allele within the IL-2 pathway that could be associated with a decrease in the microbial species of Clostridiales, Bacteroides, Lachnospiaceae, Ruminoccaceae, and Rikenellaceae [13].
The Zonulin-transgenic mouse displays behavioral alterations ameliorated via depletion of the gut microbiota
Published in Tissue Barriers, 2022
Alba Miranda-Ribera, Gloria Serena, Jundi Liu, Alessio Fasano, Marcy A. Kingsbury, Maria R. Fiorentino
We also found that the gut microbiota in both male and female Ztm mice harbor an abundance of pro-inflammatory species and is skewed toward a more maladaptive and pathogenic profile. Expansion of Rikenellaceae has been reported in obesity and diabetes and is associated with the pathological progression of inflammatory bowel disease.147–150 Moreover, low levels of A. muciniphila are positively correlated with several human diseases and this species has been shown to be a critical contributor to epithelial barrier integrity and strength.46,151–156 It is conceivable that the intrinsic defect in gut permeability in the Ztm mice allows the passage of pathobionts (commensal organisms with pathological potential) or their products into the bloodstream and across a compromised BBB, thereby contributing to the onset of a neuroinflammatory status that leads to behavioral abnormalities. Furthermore, because microbiota dysbiosis triggers zonulin secretion,39–41 the abundance of pathobionts in the gut of Ztm mice might further induce expression of zonulin in a vicious cycle.
Gut microbial communities from patients with anorexia nervosa do not influence body weight in recipient germ-free mice
Published in Gut Microbes, 2021
Elaine M. Glenny, Farnaz Fouladi, Stephanie A. Thomas, Emily C. Bulik-Sullivan, Quyen Tang, Zorka Djukic, Yesel S. Trillo-Ordonez, Anthony A. Fodor, Lisa M. Tarantino, Cynthia M. Bulik, Ian M. Carroll
Despite no differences in cecum weight between recipient mouse groups, the bacterial families Rikenellaceae and Ruminococcaceae were significantly associated with cecum weight depending on the human donor. These results further suggest that AN-associated gut microbiotas and their metabolites produced within the cecum may affect cecum physiology differently from non-AN microbiotas. However, the translational relevance of this finding is difficult to discern as the cecum in the mouse functions as a site for microbial fermentation while the cecum in humans has little fermentative capacity.31 Nonetheless, as GF mice both lack microbes for fermentation and exhibit enlarged ceca, it is tempting to speculate that AN-associated gut microbiotas are rich in microbes with elevated fermentative capacities.32 Indeed, the Rikenellaceae family (enriched in the AN-colonized mice in our study) outcompetes other common digestive tract bacteria when grown on mucin-rich media.33 Additionally, the Ruminococcaceae family (also enriched in the AN-colonized mice in our study) encompasses microbes known to produce short-chain fatty acids (SCFA) via fermentation of fiber (i.e., Faecalibacterium prausnitzii and Clostridium leptum).34,35 It has yet to be elucidated whether SCFAs play a role in AN and whether SCFA production is a compensatory response to a nutrient-deprived environment.
Elevated gut microbiome abundance of Christensenellaceae, Porphyromonadaceae and Rikenellaceae is associated with reduced visceral adipose tissue and healthier metabolic profile in Italian elderly
Published in Gut Microbes, 2021
Teresa Tavella, Simone Rampelli, Giulia Guidarelli, Alberto Bazzocchi, Chiara Gasperini, Estelle Pujos-Guillot, Blandine Comte, Monica Barone, Elena Biagi, Marco Candela, Claudio Nicoletti, Fawzi Kadi, Giuseppe Battista, Stefano Salvioli, Paul W. O’Toole, Claudio Franceschi, Patrizia Brigidi, Silvia Turroni, Aurelia Santoro
In line with the available literature, the microbial footprints of the G2 group (i.e., the greater proportion of Christensenellaceae, Porphyromonadaceae and Rikenellaceae) could contribute to a reduced amount of visceral fat mass.29,32,33 Indeed, the family Christensenellaceae has been consistently reported as negatively related to visceral fat mass and indicated as a marker of lean phenotype,29,34,35 as also shown by our sPLS regression. On the other hand, Porphyromonadaceae and Rikenellaceae members, both belonging to the Bacteroidetes phylum, could play a role as adiposity modulators through the production of the SCFAs acetate and propionate.36 Specifically, it has been shown that acetate contributes to adiposity reduction in mice, by upregulating the genes involved in fatty acid oxidation in the liver.37 Furthermore, the abundances of Christensenellaceae and Rikenellaceae have recently been found to be highly correlated with each other and significantly higher in lean than obese subjects.38