Glutamate interactions with obesity, insulin resistance, cognition and gut microbiota composition

Palomo-Buitrago, María Encarnación; Sabater-Masdeu, Mònica; Moreno-Navarrete, José María; Caballano-Infantes, Estefanía; Arnoriaga-Rodríguez, María; Coll, Clàudia; Ramió, Lluís; Palomino‐Schätzlein, Martina; Gutiérrez-Carcedo, Patricia; Pérez‐Brocal, Vicente; Simó, Rafael; Moya, Andrés; Ricart, Wifredo; Herance, José Raúl; Fernández‐Real, José Manuel

doi:10.1007/s00592-019-01313-w

Cited by 57 publications

(35 citation statements)

References 28 publications

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“…Pilot studies noted that the glutamate metabolized by gut microbiota may be associated with obesity [33], seizure [34], autism [35] and cognition [36]. A metagenome-wide association study showed that Bacteroides thetaiotaomicron was reduced in obese subjects and was inversely correlated with serum glutamate levels [33].…”

Section: Glutamate May Be Modulated By Gut Microbiotamentioning

confidence: 99%

“…Thus, lower abundance of Campylobacter jejuni may affect the synthesis of glutamate, which in turn would indirectly impact glutamate metabolism. Furthermore, a pilot study including 35 subjects showed that glutamate metabolized by gut microbiota is associated with cognitive functions such as processing speed and mental flexibility [36]. However, whether d-glutamate is modulated by gut microbiota in humans remains unclear.…”

Section: Glutamate May Be Modulated By Gut Microbiotamentioning

confidence: 99%

“…Recent studies suggest that the gut microbiota play a critical role in neurodegenerative diseases including AD or various types of dementia [31,32]. Pilot studies reported that glutamate metabolized by gut microbiota can be linked to obesity [33], seizure [34], autism [35] and cognition [36,37]. This review's purpose is to discuss the involvement of glutamatergic neurotransmission and gut microbiota in AD, focusing on the contribution of NMDAR signaling in AD.…”

Section: Introductionmentioning

confidence: 99%

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d-glutamate and Gut Microbiota in Alzheimer’s Disease

Chang

Lin

Lane

2020

IJMS

116

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Background: An increasing number of studies have shown that the brain–gut–microbiota axis may significantly contribute to Alzheimer’s disease (AD) pathogenesis. Moreover, impaired memory and learning involve the dysfunction neurotransmission of glutamate, the agonist of the N-methyl-d-aspartate receptor and a major excitatory neurotransmitter in the brain. This systematic review aimed to summarize the current cutting-edge research on the gut microbiota and glutamate alterations associated with dementia. Methods: PubMed, the Cochrane Collaboration Central Register of Controlled Clinical Trials, and Cochrane Systematic Reviews were reviewed for all studies on glutamate and gut microbiota in dementia published up until Feb 2020. Results: Several pilot studies have reported alterations of gut microbiota and metabolites in AD patients and other forms of dementia. Gut microbiota including Bacteroides vulgatus and Campylobacter jejuni affect glutamate metabolism and decrease the glutamate metabolite 2-keto-glutaramic acid. Meanwhile, gut bacteria with glutamate racemase including Corynebacterium glutamicum, Brevibacterium lactofermentum, and Brevibacterium avium can convert l-glutamate to d-glutamate. N-methyl-d-aspartate glutamate receptor (NMDAR)-enhancing agents have been found to potentially improve cognition in AD or Parkinson’s disease patients. These findings suggest that d-glutamate (d-form glutamate) metabolized by the gut bacteria may influence the glutamate NMDAR and cognitive function in dementia patients. Conclusions: Gut microbiota and glutamate are potential novel interventions to be developed for dementia. Exploring comprehensive cognitive functions in animal and human trials with glutamate-related NMDAR enhancers are warranted to examine d-glutamate signaling efficacy in gut microbiota in patients with AD and other neurodegenerative dementias.

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Section: Glutamate May Be Modulated By Gut Microbiotamentioning

confidence: 99%

Section: Glutamate May Be Modulated By Gut Microbiotamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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d-glutamate and Gut Microbiota in Alzheimer’s Disease

Chang

Lin

Lane

2020

IJMS

116

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“…82,83 Alteration of plasma BCAA metabolism, for instance, was found to result in accumulation of toxic metabolites, which subsequently trigger mitochondrial dysfunction and stress signaling associated with insulin resistance. 84,85 In our study, we found that Hispanic, when compared to non-Hispanic, had greater abundance of distinct fecal amino acids, including BCAA (leucine, isoleucine, valine), AAA (phenylalanine, threonine, tryptophan), other essential amino acids (histidine, lysine, methionine), and certain non-essential amino acids (glycine, tyrosine, serine, alanine, glutamate). Amino acids profiles were similar among other studied covariates.…”

Section: Discussionmentioning

confidence: 56%

Moving toward precision: Understanding the heterogeneity of obesity.

Hung

Dong

Elashoff

et al. 2020

JCO

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12054 Background: Obesity is a global health epidemic and has been linked to detrimental impact on cancer incidence, recurrence, and mortality. Growing evidence have recognized the complex biopsychosocial relationship including microbial phenotypes that undermines the carcinogenic potential and heterogeneity of obesity. A precision understanding on obesity while at its infancy is necessary to accelerate reduction of its impact on cancer outcomes. Methods: With our aim to better understand the biopsychosocial relationship on obesity, we conducted a cross sectional study in healthy and obese individuals. Univariate and multivariate logistic regression models were used to examine obesity and its association with sociodemographic (age, gender, ethnicity, education, income, and marital status), clinical (waist to hip ratio), dietary-behavioral (daily calorie, fat, carbohydrate, protein consumption, and preference on cultural diet), and biological factors (gut microbiome). Parameters were controlled and corrected for multiple hypothesis testing. Gut microbial data using 16S rRNA sequencing were analyzed for alpha diversity, beta diversity, and association of taxa abundance. Results: Among 171 participants between July 2013 and August 2018, individuals were found to have a higher BMI if they were Hispanic [Adjusted Odds Ratio (AOR) 3.36, 95% CI 1.27-8.90], had an obese waist to hip ratio (AOR 8.51, 95% CI 3.45-21.02), and consumed an American diet (AOR 4.82, 95% CI 1.74-13.34). Multivariate permutation analysis controlling for BMI, sociodemographic, clinical, and dietary parameters found that Hispanic have a significantly different microbiome profile than non-Hispanic (p = 0.042). While microbial species richness (Chao1) were similar (p = 0.22), Hispanic had a lower microbial species evenness (Shannon) compared to non-Hispanic (p = 0.029). Differential expression of microbial species revealed a positive correlation of Firmicutes:Bacteroidetes ratio in individuals with higher BMI and consumed an American diet whereas a negative correlation to Hispanic ethnicity. Conclusions: Obesity association to Hispanic ethnicity uniquely expressed through microbial signature despite sociodemographic, clinical, and dietary differences. Microbial characterization as an emerging predictive marker for oncology therapeutics may also serve as selection biomarker in onco-obesity practices and clinical trials. Addressing ethnic disparities guided by microbial phenotypes may unlock novel understanding of obesity heterogeneity and transform its impact on cancer care.

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“…Dumas and colleagues discussed the relevance of Diet-Induced Metabolic Changes of the Human Gut Microbiome and in particular they focus on microbie-derived metabolites such as short-chain fatty acids, methylamines and indoles [19]. Fernandez Real and colleagues showed new evidence connecting glutamate to gut microbiota composition and metabolic phenotypes [20]. Finally, Liang Ma and colleagues illustrated the links between gut microbiota and diabetic nephropathy [21].…”

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confidence: 99%

Our second genome and the impact on metabolic disorders: why gut microbiome is an important player in diabetes and associated abnormalities

Federici

2019

Acta Diabetol

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Glutamate interactions with obesity, insulin resistance, cognition and gut microbiota composition

Cited by 57 publications

References 28 publications

d-glutamate and Gut Microbiota in Alzheimer’s Disease

d-glutamate and Gut Microbiota in Alzheimer’s Disease

Moving toward precision: Understanding the heterogeneity of obesity.

Our second genome and the impact on metabolic disorders: why gut microbiome is an important player in diabetes and associated abnormalities

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