scholarly journals Gestational insulin resistance is mediated by the gut microbiome-indoleamine 2,3-dioxygenase axis

2021 ◽  
Author(s):  
Medha Priyadarshini ◽  
Guadalupe Navarro ◽  
Derek Reiman ◽  
Anukriti Sharma ◽  
Kai Xu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Gut Microbiome ◽  
Intestinal Inflammation ◽  
Alpha Diversity ◽  
Mouse Strains ◽  
Indoleamine 2,3 Dioxygenase ◽  
Plasma Metabolome ◽  
Maternal Metabolism ◽  
Nih Swiss ◽  
Normal Gestation

Background and aims: Normal gestation involves reprogramming of maternal gut microbiome (GM) that may contribute to maternal metabolic changes by unclear mechanisms. This study aimed to understand the mechanistic underpinnings of GM maternal metabolism interaction. Methods: The GM and plasma metabolome of CD1, NIH Swiss and C57BL/6J mice were analyzed using 16S rRNA sequencing and untargeted LC-MS throughout gestation and postpartum. Pharmacologic and genetic knockout mouse models were used to identify the role of indoleamine 2,3-dioxygenase (IDO1) in pregnancy-associated insulin resistance (IR). Involvement of gestational GM in the process was studied using fecal microbial transplants (FMT). Results: Significant variation in gut microbial alpha diversity occurred throughout pregnancy. Enrichment in gut bacterial taxa was mouse strain and pregnancy time-point specific, with species enriched at gestation day 15/19 (G15/19), a point of heightened IR, distinct from those enriched pre- or post-pregnancy. Untargeted and targeted metabolomics revealed elevated plasma kynurenine at G15/19 in all three mouse strains. IDO1, the rate limiting enzyme for kynurenine production, had increased intestinal expression at G15, which was associated with mild systemic and gut inflammation. Pharmacologic and genetic inhibition of IDO1 inhibited kynurenine levels and reversed pregnancy-associated IR. FMT revealed that IDO1 induction and local kynurenine levels effects on IR derive from the GM in both mouse and human pregnancy. Conclusions: GM changes accompanying pregnancy shift IDO1 dependent tryptophan metabolism toward kynurenine production, intestinal inflammation and gestational IR, a phenotype reversed by genetic deletion or inhibition of IDO1.

scholarly journals An interventional Soylent diet increases the Bacteroidetes to Firmicutes ratio in human gut microbiome communities: a randomized controlled trial

2017 ◽  
Author(s):  
Ryan H. Hsu ◽  
Dylan M. McCormick ◽  
Mitchell J. Seitz ◽  
Lauren M. Lui ◽  
Harneet S. Rishi ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Intestinal Inflammation ◽  
Controlled Trial ◽  
Alpha Diversity ◽  
Diet Group ◽  
Positive Health ◽  
Unifrac Distance ◽  
Liquid Meal ◽  
Regular Diet ◽  
Rdna Sequencing

AbstractOur knowledge of the relationship between the gut microbiome and health has rapidly expanded in recent years. Diet has been shown to have causative effects on microbiome composition, which can have subsequent implications on health. Soylent 2.0 is a liquid meal replacement drink that satisfies nearly 20% of all recommended daily intakes per serving. This study aims to characterize the changes in gut microbiota composition resulting from a short-term Soylent diet. Fourteen participants were separated into two groups: 5 in the regular diet group and 9 in the Soylent diet group. The regular diet group maintained a diet closely resembling self-reported regular diets. The Soylent diet group underwent three dietary phases: A) a regular diet for 2 days, B) a Soylent-only diet (five servings of Soylent daily and water as needed) for 4 days, and C) a regular diet for 4 days. Daily logs self-reporting diet, Bristol stool ratings, and any abdominal discomfort were electronically submitted. Eight fecal samples per participant were collected using fecal sampling kits, which were subsequently sent to uBiome, Inc. for sample processing and V4 16S rDNA sequencing. Reads were clustered into operational taxonomic units (OTUs) and taxonomically identified against the GreenGenes 16S database. We find that an individual’s alpha-diversity is not significantly altered during a Soylent-only diet. In addition, principal coordinate analysis using the unweighted UniFrac distance metric shows samples cluster strongly by individual and not by dietary phase. Among Soylent dieters, we find a significant increase in the ratio of Bacteroidetes to Firmicutes abundance, which is associated with several positive health outcomes, including reduced risks of obesity and intestinal inflammation.

scholarly journals Gestational insulin resistance is mediated by the gut microbiome-indoleamine 2,3-dioxygenase axis

2022 ◽  
Author(s):  
Medha Priyadarshini ◽  
Guadalupe Navarro ◽  
Derek J. Reiman ◽  
Anukriti Sharma ◽  
Kai Xu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Gut Microbiome ◽  
Indoleamine 2,3 Dioxygenase

scholarly journals Multi ‘Omics Analysis of Intestinal Tissue in Ankylosing Spondylitis Identifies Alterations in the Tryptophan Metabolism Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Adam J. Berlinberg ◽  
Emilie H. Regner ◽  
Andrew Stahly ◽  
Ana Brar ◽  
Julie A. Reisz ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Intestinal Inflammation ◽  
Alpha Diversity ◽  
Distal Colon ◽  
Tryptophan Metabolism ◽  
Genetic Changes ◽  
Shotgun Metagenomics ◽  
Fecal Samples ◽  
Disease States ◽  
Microbial Dysbiosis

Intestinal microbial dysbiosis, intestinal inflammation, and Th17 immunity are all linked to the pathophysiology of spondyloarthritis (SpA); however, the mechanisms linking them remain unknown. One potential hypothesis suggests that the dysbiotic gut microbiome as a whole produces metabolites that influence human immune cells. To identify potential disease-relevant, microbiome-produced metabolites, we performed metabolomics screening and shotgun metagenomics on paired colon biopsies and fecal samples, respectively, from subjects with axial SpA (axSpA, N=21), Crohn’s disease (CD, N=27), and Crohn’s-axSpA overlap (CD-axSpA, N=12), as well as controls (HC, N=24). Using LC-MS based metabolomics of 4 non-inflamed pinch biopsies of the distal colon from subjects, we identified significant alterations in tryptophan pathway metabolites, including an expansion of indole-3-acetate (IAA) in axSpA and CD-axSpA compared to HC and CD and indole-3-acetaldehyde (I3Ald) in axSpA and CD-axSpA but not CD compared to HC, suggesting possible specificity to the development of axSpA. We then performed shotgun metagenomics of fecal samples to characterize gut microbial dysbiosis across these disease states. In spite of no significant differences in alpha-diversity among the 4 groups, our results confirmed differences in gene abundances of numerous enzymes involved in tryptophan metabolism. Specifically, gene abundance of indolepyruvate decarboxylase, which generates IAA and I3Ald, was significantly elevated in individuals with axSpA while gene abundances in HC demonstrated a propensity towards tryptophan synthesis. Such genetic changes were not observed in CD, again suggesting disease specificity for axSpA. Given the emerging role of tryptophan and its metabolites in immune function, altogether these data indicate that tryptophan metabolism into I3Ald and then IAA is one mechanism by which the gut microbiome potentially influences the development of axSpA.

scholarly journals Effects of Immunization With the Soil-Derived Bacterium Mycobacterium vaccae on Stress Coping Behaviors and Cognitive Performance in a “Two Hit” Stressor Model

2021 ◽  
Vol 11 ◽  
Author(s):  
Christine L. Foxx ◽  
Jared D. Heinze ◽  
Antonio González ◽  
Fernando Vargas ◽  
Michael V. Baratta ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Alpha Diversity ◽  
Object Location ◽  
Exposure Model ◽  
Rrna Gene ◽  
Stress Exposure ◽  
Mycobacterium Vaccae ◽  
Location Memory ◽  
Object Location Memory ◽  
Plasma Metabolome

Previous studies demonstrate that Mycobacterium vaccae NCTC 11659 (M. vaccae), a soil-derived bacterium with anti-inflammatory and immunoregulatory properties, is a potentially useful countermeasure against negative outcomes to stressors. Here we used male C57BL/6NCrl mice to determine if repeated immunization with M. vaccae is an effective countermeasure in a “two hit” stress exposure model of chronic disruption of rhythms (CDR) followed by acute social defeat (SD). On day –28, mice received implants of biotelemetric recording devices to monitor 24-h rhythms of locomotor activity. Mice were subsequently treated with a heat-killed preparation of M. vaccae (0.1 mg, administered subcutaneously on days –21, –14, –7, and 27) or borate-buffered saline vehicle. Mice were then exposed to 8 consecutive weeks of either stable normal 12:12 h light:dark (LD) conditions or CDR, consisting of 12-h reversals of the LD cycle every 7 days (days 0–56). Finally, mice were exposed to either a 10-min SD or a home cage control condition on day 54. All mice were exposed to object location memory testing 24 h following SD. The gut microbiome and metabolome were assessed in fecal samples collected on days –1, 48, and 62 using 16S rRNA gene sequence and LC-MS/MS spectral data, respectively; the plasma metabolome was additionally measured on day 64. Among mice exposed to normal LD conditions, immunization with M. vaccae induced a shift toward a more proactive behavioral coping response to SD as measured by increases in scouting and avoiding an approaching male CD-1 aggressor, and decreases in submissive upright defensive postures. In the object location memory test, exposure to SD increased cognitive function in CDR mice previously immunized with M. vaccae. Immunization with M. vaccae stabilized the gut microbiome, attenuating CDR-induced reductions in alpha diversity and decreasing within-group measures of beta diversity. Immunization with M. vaccae also increased the relative abundance of 1-heptadecanoyl-sn-glycero-3-phosphocholine, a lysophospholipid, in plasma. Together, these data support the hypothesis that immunization with M. vaccae stabilizes the gut microbiome, induces a shift toward a more proactive response to stress exposure, and promotes stress resilience.

Indoleamine 2,3 dioxygenase downregulates intestinal inflammation

2001 ◽  
Vol 120 (5) ◽  
pp. A182-A182
Author(s):  
G GREGORY ◽  
W STENSON ◽  
R NEWBERRY
Keyword(s):  
Intestinal Inflammation ◽  
Indoleamine 2,3 Dioxygenase

Folate and vitamin B-12 deficiencies additively impaired memory function and disturbed the gut microbiota in amyloid-β infused rats

2019 ◽  
pp. 1-13 ◽  
Author(s):  
Sunmin Park ◽  
Sunna Kang ◽  
Da Sol Kim
Keyword(s):  
Insulin Resistance ◽  
Gut Microbiota ◽  
Insulin Signaling ◽  
Gut Microbiome ◽  
Metabolic Diseases ◽  
Memory Function ◽  
Amyloid Β ◽  
Impaired Memory ◽  
Ca1 Region ◽  
Folate And Vitamin B12

Abstract. Folate and vitamin B12(V-B12) deficiencies are associated with metabolic diseases that may impair memory function. We hypothesized that folate and V-B12 may differently alter mild cognitive impairment, glucose metabolism, and inflammation by modulating the gut microbiome in rats with Alzheimer’s disease (AD)-like dementia. The hypothesis was examined in hippocampal amyloid-β infused rats, and its mechanism was explored. Rats that received an amyloid-β(25–35) infusion into the CA1 region of the hippocampus were fed either control(2.5 mg folate plus 25 μg V-B12/kg diet; AD-CON, n = 10), no folate(0 folate plus 25 μg V-B12/kg diet; AD-FA, n = 10), no V-B12(2.5 mg folate plus 0 μg V-B12/kg diet; AD-V-B12, n = 10), or no folate plus no V-B12(0 mg folate plus 0 μg V-B12/kg diet; AD-FAB12, n = 10) in high-fat diets for 8 weeks. AD-FA and AD-VB12 exacerbated bone mineral loss in the lumbar spine and femur whereas AD-FA lowered lean body mass in the hip compared to AD-CON(P < 0.05). Only AD-FAB12 exacerbated memory impairment by 1.3 and 1.4 folds, respectively, as measured by passive avoidance and water maze tests, compared to AD-CON(P < 0.01). Hippocampal insulin signaling and neuroinflammation were attenuated in AD-CON compared to Non-AD-CON. AD-FAB12 impaired the signaling (pAkt→pGSK-3β) and serum TNF-α and IL-1β levels the most among all groups. AD-CON decreased glucose tolerance by increasing insulin resistance compared to Non-AD-CON. AD-VB12 and AD-FAB12 increased insulin resistance by 1.2 and 1.3 folds, respectively, compared to the AD-CON. AD-CON and Non-AD-CON had a separate communities of gut microbiota. The relative counts of Bacteroidia were lower and those of Clostridia were higher in AD-CON than Non-AD-CON. AD-FA, but not V-B12, separated the gut microbiome community compared to AD-CON and AD-VB12(P = 0.009). In conclusion, folate and B-12 deficiencies impaired memory function by impairing hippocampal insulin signaling and gut microbiota in AD rats.

scholarly journals Gut microbiome composition in the Hispanic Community Health Study/Study of Latinos is shaped by geographic relocation, environmental factors, and obesity

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Robert C. Kaplan ◽  
Zheng Wang ◽  
Mykhaylo Usyk ◽  
Daniela Sotres-Alvarez ◽  
Martha L. Daviglus ◽  
...  
Keyword(s):  
Community Health ◽  
Gut Microbiome ◽  
Alpha Diversity ◽  
Amplicon Sequencing ◽  
Shannon Index ◽  
Health Study ◽  
Rrna Gene ◽  
Cross Sectional ◽  
Hispanic Community ◽  
The Usa

Abstract Background Hispanics living in the USA may have unrecognized potential birthplace and lifestyle influences on the gut microbiome. We report a cross-sectional analysis of 1674 participants from four centers of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), aged 18 to 74 years old at recruitment. Results Amplicon sequencing of 16S rRNA gene V4 and fungal ITS1 fragments from self-collected stool samples indicate that the host microbiome is determined by sociodemographic and migration-related variables. Those who relocate from Latin America to the USA at an early age have reductions in Prevotella to Bacteroides ratios that persist across the life course. Shannon index of alpha diversity in fungi and bacteria is low in those who relocate to the USA in early life. In contrast, those who relocate to the USA during adulthood, over 45 years old, have high bacterial and fungal diversity and high Prevotella to Bacteroides ratios, compared to USA-born and childhood arrivals. Low bacterial diversity is associated in turn with obesity. Contrasting with prior studies, our study of the Latino population shows increasing Prevotella to Bacteroides ratio with greater obesity. Taxa within Acidaminococcus, Megasphaera, Ruminococcaceae, Coriobacteriaceae, Clostridiales, Christensenellaceae, YS2 (Cyanobacteria), and Victivallaceae are significantly associated with both obesity and earlier exposure to the USA, while Oscillospira and Anaerotruncus show paradoxical associations with both obesity and late-life introduction to the USA. Conclusions Our analysis of the gut microbiome of Latinos demonstrates unique features that might be responsible for health disparities affecting Hispanics living in the USA.

scholarly journals Endocannabinoid system mediates the association between gut-microbial diversity and anhedonia/amotivation in a general population cohort

2021 ◽  
Author(s):  
Amedeo Minichino ◽  
Matthew A. Jackson ◽  
Marta Francesconi ◽  
Claire J. Steves ◽  
Cristina Menni ◽  
...  
Keyword(s):  
General Population ◽  
Microbial Diversity ◽  
Gut Microbiome ◽  
Endocannabinoid System ◽  
Alpha Diversity ◽  
Serum Levels ◽  
Population Cohort ◽  
Random Intercept ◽  
General Population Cohort ◽  
Antidepressant Use

AbstractAnhedonia and amotivation are debilitating symptoms and represent unmet therapeutic needs in a range of clinical conditions. The gut-microbiome-endocannabinoid axis might represent a potential modifiable target for interventions. Based on results obtained from animal models, we tested the hypothesis that the endocannabinoid system mediates the association between gut-microbiome diversity and anhedonia/amotivation in a general population cohort. We used longitudinal data collected from 786 volunteer twins recruited as part the TwinsUK register. Our hypothesis was tested with a multilevel mediation model using family structure as random intercept. The model was set using alpha diversity (within-individual gut-microbial diversity) as predictor, serum and faecal levels of the endocannabinoid palmitoylethanolamide (PEA) as mediator, and anhedonia/amotivation as outcome. PEA is considered the endogenous equivalent of cannabidiol, with increased serum levels believed to have anti-depressive effects, while increased stool PEA levels, reflecting increased excretion, are believed to have opposite, detrimental, effects on mental health. We therefore expected that either reduced serum PEA or increased stool PEA would mediate the association between microbial diversity and anhedonia amotivation. Analyses were adjusted for obesity, diet, antidepressant use, sociodemographic and technical covariates. Data were imputed using multiple imputation by chained equations. Mean age was 65.2 ± 7.6; 93% of the sample were females. We found a direct, significant, association between alpha diversity and anhedonia/amotivation (β = −0.37; 95%CI: −0.71 to −0.03; P = 0.03). Faecal, but not serum, levels of the endocannabinoid palmitoylethanolamide (PEA) mediated this association: the indirect effect was significant (β = −0.13; 95%CI: −0.24 to −0.01; P = 0.03), as was the total effect (β = −0.38; 95%CI: −0.72 to −0.04; P = 0.03), whereas the direct effect of alpha diversity on anhedonia/amotivation was attenuated fully (β = −0.25; 95%CI: −0.60 to 0.09; P = 0.16). Our results suggest that gut-microbial diversity might contribute to anhedonia/amotivation via the endocannabinoid system. These findings shed light on the biological underpinnings of anhedonia/amotivation and suggest the gut microbiota-endocannabinoid axis as a promising therapeutic target in an area of unmet clinical need.

scholarly journals γ-PGA-Rich Chungkookjang, Short-Term Fermented Soybeans: Prevents Memory Impairment by Modulating Brain Insulin Sensitivity, Neuro-Inflammation, and the Gut–Microbiome–Brain Axis

Foods ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 221
Author(s):  
Do-Youn Jeong ◽  
Myeong Seon Ryu ◽  
Hee-Jong Yang ◽  
Sunmin Park
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Gut Microbiome ◽  
Memory Impairment ◽  
Memory Function ◽  
Bacillus Species ◽  
Fermented Foods ◽  
Short Term ◽  
Brain Insulin ◽  
Brain Insulin Resistance

Fermented soybean paste is an indigenous food for use in cooking in East and Southeast Asia. Korea developed and used its traditional fermented foods two thousand years ago. Chungkookjang has unique characteristics such as short-term fermentation (24–72 h) without salt, and fermentation mostly with Bacilli. Traditionally fermented chungkookjang (TFC) is whole cooked soybeans that are fermented predominantly by Bacillus species. However, Bacillus species are different in the environment according to the regions and seasons due to the specific bacteria. Bacillus species differently contribute to the bioactive components of chungkookjang, resulting in different functionalities. In this review, we evaluated the production process of poly-γ-glutamic acid (γ-PGA)-rich chungkookjang fermented with specific Bacillus species and their effects on memory function through the modulation of brain insulin resistance, neuroinflammation, and the gut–microbiome–brain axis. Bacillus species were isolated from the TFC made in Sunchang, Korea, and they included Bacillus (B.) subtilis, B. licheniformis, and B. amyloliquefaciens. Chungkookjang contains isoflavone aglycans, peptides, dietary fiber, γ-PGA, and Bacillus species. Chungkookjangs made with B. licheniformis and B. amyloliquefaciens have higher contents of γ-PGA, and they are more effective for improving glucose metabolism and memory function. Chungkookjang has better efficacy for reducing inflammation and oxidative stress than other fermented soy foods. Insulin sensitivity is improved, not only in systemic organs such as the liver and adipose tissues, but also in the brain. Chungkookjang intake prevents and alleviates memory impairment induced by Alzheimer’s disease and cerebral ischemia. This review suggests that the intake of chungkookjang (20–30 g/day) rich in γ-PGA acts as a synbiotic in humans and promotes memory function by suppressing brain insulin resistance and neuroinflammation and by modulating the gut–microbiome–brain axis.

scholarly journals Meta-analysis of the Parkinson’s disease gut microbiome suggests alterations linked to intestinal inflammation

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Stefano Romano ◽  
George M. Savva ◽  
Janis R. Bedarf ◽  
Ian G. Charles ◽  
Falk Hildebrand ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Fatty Acids ◽  
Parkinson's Disease ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Intestinal Inflammation ◽  
Meta Analysis ◽  
Gastrointestinal Symptoms ◽  
Short Chain Fatty Acids ◽  
Inflammatory Status

AbstractThe gut microbiota is emerging as an important modulator of neurodegenerative diseases, and accumulating evidence has linked gut microbes to Parkinson’s disease (PD) symptomatology and pathophysiology. PD is often preceded by gastrointestinal symptoms and alterations of the enteric nervous system accompany the disease. Several studies have analyzed the gut microbiome in PD, but a consensus on the features of the PD-specific microbiota is missing. Here, we conduct a meta-analysis re-analyzing the ten currently available 16S microbiome datasets to investigate whether common alterations in the gut microbiota of PD patients exist across cohorts. We found significant alterations in the PD-associated microbiome, which are robust to study-specific technical heterogeneities, although differences in microbiome structure between PD and controls are small. Enrichment of the genera Lactobacillus, Akkermansia, and Bifidobacterium and depletion of bacteria belonging to the Lachnospiraceae family and the Faecalibacterium genus, both important short-chain fatty acids producers, emerged as the most consistent PD gut microbiome alterations. This dysbiosis might result in a pro-inflammatory status which could be linked to the recurrent gastrointestinal symptoms affecting PD patients.

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