Detangling Diet from Obesity Effects on the Gut Microbiome and Metabolic Parameters Using a Non-Human Primate Model

Abstract Objectives Poor diet and obesity often go hand-in-hand and are difficult to discern which variable is the major driver of the gut microbiome. The objective of this study was to determine the impact of obesity within dietary exposures on the gut microbiome and metabolic parameters using a non-human primate model. Methods Female M. fasicularis monkeys were fed a Western or Mediterranean diet for 2.5 years. We performed metagenomics sequencing on fecal samples obtained at 26 months. DNA was isolated from feces using Qiagen PowerSoil DNA extraction kit and metagenomics sequencing was performed for multikingdom microbiome analysis. DEXA scans for body adiposity and metabolic profiling were measured in each subject before the end of the study. Subjects were grouped by body fat composition (Lean (≤10% body fat) or Overweight/Obese (≥20% body fat)) and the impact of diet and adiposity was determine on the gut microbiome. Gut microbiota populations were correlated with metabolic parameters. Results Diet is the main determinant on gut microbiome α-diversity. Obesity had no significant outcome on Shannon diversity. Obesity within each dietary pattern can influence certain gut microbes. Lean Mediterranean diet-fed animals had significantly higher L. animals and C. comes that overweight animals fed the same diet. Obese Western diet-fed animals displayed elevated proportional abundance of S. infantarius and R. chanpaneliensis that lean Western diet-fed animals. Independent of adiposity, Western diet consumption lead to two distinct microbiome populations; P. copri high and P. copri low. P. copriHIGH displayed reduced α-diversity, increased abundance of other Prevotella species (P. stercorea, P. brevis, and P. bryantii), and increased F. prausnitzii. P. copri negatively correlated with α-diversity. P. copriLOW displayed increased proportional abundance of E. siraeum. Gut E. siraeum populations positively correlated with plasma HDL cholesterol levels. Conclusions Our data indicates that diet is a potent regulator of the gut microbiome, while body adiposity can subtly shift specific gut microbiota taxa within subjects fed a specific dietary pattern. Moreover, our data indicates at a sub-group of metabolically healthier subjects on a Western diet characterized by low P. copri microbiota abundance. Funding Sources NIH and DOD BCRP.

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Neonatal Immune System Ontogeny: The Role of Maternal Microbiota and Associated Factors. How Might the Non-Human Primate Model Enlighten the Path?

Vaccines ◽

10.3390/vaccines9060584 ◽

2021 ◽

Vol 9 (6) ◽

pp. 584

Author(s):

Natalia Nunez ◽

Louis Réot ◽

Elisabeth Menu

Keyword(s):

Immune System ◽

Mode Of Delivery ◽

Microbial Colonization ◽

Therapeutic Interventions ◽

Primate Model ◽

Neonatal Immune System ◽

Gastrointestinal Colonization ◽

The Impact ◽

Human Primate

Interactions between the immune system and the microbiome play a crucial role on the human health. These interactions start in the prenatal period and are critical for the maturation of the immune system in newborns and infants. Several factors influence the composition of the infant’s microbiota and subsequently the development of the immune system. They include maternal infection, antibiotic treatment, environmental exposure, mode of delivery, breastfeeding, and food introduction. In this review, we focus on the ontogeny of the immune system and its association to microbial colonization from conception to food diversification. In this context, we give an overview of the mother–fetus interactions during pregnancy, the impact of the time of birth and the mode of delivery, the neonate gastrointestinal colonization and the role of breastfeeding, weaning, and food diversification. We further review the impact of the vaccination on the infant’s microbiota and the reciprocal case. Finally, we discuss several potential therapeutic interventions that might help to improve the newborn and infant’s health and their responses to vaccination. Throughout the review, we underline the main scientific questions that are left to be answered and how the non-human primate model could help enlighten the path.

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The Impact of Chronic Marijuana Exposure on Fetal Development in a Non-Human Primate Model

American Journal of Obstetrics and Gynecology ◽

10.1016/j.ajog.2021.11.264 ◽

2022 ◽

Vol 226 (1) ◽

pp. S150

Author(s):

Rahul J. D'Mello ◽

Victoria H. Roberts ◽

Xiaojie Wang ◽

Juanito D. Terrobias ◽

Jamie O. Lo

Keyword(s):

Fetal Development ◽

Primate Model ◽

The Impact ◽

Human Primate

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SUN-637 The Impact of Hyperandrogenemia and Western-Style Diet on Post-Pregnancy Metabolism in Nonhuman Primates

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1274 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Diana Lynn Takahashi ◽

Emily Mishler ◽

Ov Daniel Slayden ◽

Jon D Hennebold ◽

Charles T Roberts ◽

...

Keyword(s):

Insulin Resistance ◽

Body Fat ◽

Glucose Homeostasis ◽

Polycystic Ovary ◽

Mean Value ◽

Fat Percentage ◽

Primate Model ◽

Intravenous Glucose ◽

Intravenous Glucose Tolerance Tests ◽

The Impact

Abstract Polycystic ovary syndrome (PCOS) often is associated with hyperandrogenemia and an increased incidence of obesity and type 2 diabetes. To understand the separate and combined effects of androgens and obesity on reproductive and metabolic parameters, our group established a nonhuman primate model consisting of animals receiving either testosterone (T, mean value of 1.4 ng/mL), an obesogenic western-style diet (WSD, 36% of calories from fat compared to 16% in normal monkey chow), or a combination of T+WSD. T+WSD increased insulin resistance compared to WSD alone after three years of treatment and reduced fertility. Those T+WSD animals that became pregnant had a mild worsening of glucose homeostasis during pregnancy. The current study sought to determine how T+WSD affected post-pregnancy metabolic health and whether T+WSD led to the worsening of insulin resistance after pregnancy. Intravenous glucose tolerance tests (ivGTT) were performed 1) before pregnancy, 2) approximately 3-4 months after C-section, which occurred between gestational day 130-135 (3rd trimester), and 3) one year post C-section. All animal groups tended to show increases in weight, BMI, and body fat percentage after pregnancy. Both WSD groups (WSD and T+WSD) had higher overall weights, BMI, and body fat percentages. Measures of insulin sensitivity such as fasting insulin, glucose, and insulin area under the curves during an ivGTT and homeostatic model of insulin resistance (HOMA-IR) all increased over time, but there were no differences between groups. The lack of treatment effect on measures of insulin resistance may be due to the fact that animals that did not become pregnant had significantly higher indices of insulin resistance. Experimental animals underwent a second round of fertility trials thereby allowing for a comparison of glucose homeostasis for those animals that became pregnant in both the 1st and 2nd trial. The WSD group demonstrated increased fasting glucose and glucose AUC during an early third trimester ivGTT in the second pregnancy compared to the first. The control, T, and T+WSD groups did not show significant differences in glucose homeostasis between the first and second pregnancy. These findings indicate that WSD consumption may increase the risk of worsened glucose homeostasis after pregnancy and during subsequent pregnancies. Testosterone, either in isolation or in combination with WSD, did not appear to have a significant impact on post-pregnancy metabolism or worsen metabolic outcomes in a second pregnancy.

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The gut-microbiota-brain axis in autism: what Drosophila models can offer?

Journal of Neurodevelopmental Disorders ◽

10.1186/s11689-021-09378-x ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Safa Salim ◽

Ayesha Banu ◽

Amira Alwa ◽

Swetha B. M. Gowda ◽

Farhan Mohammad

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Neurological Disorders ◽

Autism Spectrum ◽

Brain Disorders ◽

Mediated Communication ◽

The Impact ◽

Insight Into ◽

Drosophila Models

AbstractThe idea that alterations in gut-microbiome-brain axis (GUMBA)-mediated communication play a crucial role in human brain disorders like autism remains a topic of intensive research in various labs. Gastrointestinal issues are a common comorbidity in patients with autism spectrum disorder (ASD). Although gut microbiome and microbial metabolites have been implicated in the etiology of ASD, the underlying molecular mechanism remains largely unknown. In this review, we have summarized recent findings in human and animal models highlighting the role of the gut-brain axis in ASD. We have discussed genetic and neurobehavioral characteristics of Drosophila as an animal model to study the role of GUMBA in ASD. The utility of Drosophila fruit flies as an amenable genetic tool, combined with axenic and gnotobiotic approaches, and availability of transgenic flies may reveal mechanistic insight into gut-microbiota-brain interactions and the impact of its alteration on behaviors relevant to neurological disorders like ASD.

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Prospective correlation between the patient microbiome with response to and development of immune-mediated adverse effects to immunotherapy in lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e21024 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e21024-e21024

Author(s):

Justin Chau ◽

Meeta Yadav ◽

Ben Liu ◽

Muhammad Furqan ◽

Qun Dai ◽

...

Keyword(s):

Lung Cancer ◽

Gut Microbiota ◽

Treatment Response ◽

Gut Microbiome ◽

Operational Taxonomic Unit ◽

Geographic Region ◽

Organ Function ◽

Immune Mediated ◽

Α Diversity ◽

Clinical Trial Information

e21024 Background: Though the gut microbiome has been associated with immunotherapy (ICI) efficacy in certain cancers, similar correlations between microbiomes at other body sites with treatment response and immune related adverse events (irAEs) in lung cancer (LC) patients receiving ICIs have not been made. We designed a prospective cohort study conducted from 2018-2020 at a single-center academic institution to assess for correlations between the microbiome in various body sites with treatment response and development of irAEs in LC patients treated with ICIs. Methods: Patients with histopathologically confirmed, unresectable/advanced/metastatic LC planned to undergo ICI-based therapy were enrolled between September 2018 and June 2019. Patients must have had measurable disease, ECOG 0-2, and good organ function to be included. Data was collected for analysis from January 2019 to October 2020. Nasal, buccal and gut microbiome samples were obtained prior to ICI initiation, at development of irAEs, improvement of irAEs to grade 1 or less, and at disease progression. 16S rRNA sequenced data was mapped to the SILVA 13.2 database; operational taxonomic unit clusters were analyzed using MicrobiomeAnalyst and METAGENassist. Results: 37 patients were enrolled, and 34 patients were evaluable for this report. 32 healthy controls (HC) from the same geographic region were included to compare baseline gut microbiota. Compared to HC, LC gut microbiota exhibited significantly lower α-diversity. The gut microbiome of patients who did not suffer irAEs were found to have relative enrichment of Bifidobacterium ( p = 0.001) and Desulfovibrio ( p = 0.0002). Responders to combined chemoimmunotherapy exhibited increased Clostridiales ( p = 0.018) but reduced Rikenellaceae ( p = 0.016). In responders to chemoimmunotherapy we also observed enrichment of Finegoldia in nasal microbiome, and increased Megasphaera but reduced Actinobacillus in buccal samples. Longitudinal samples exhibited a trend of α-diversity and certain microbial changes during the development and resolution of irAEs. Conclusions: This pilot study identified significant differences in the gut microbiome between HC and LC patients, and correlates specific bacterial genera to ICI response and irAEs in LC. In addition, it suggests potential predictive utility in nasal and buccal microbiomes, warranting further validation with a larger cohort and mechanistic dissection using preclinical models. Clinical trial information: NCT03688347.

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Role of the gut microbiota in airway immunity and host defense against respiratory infections

Biological Chemistry ◽

10.1515/hsz-2021-0281 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Maike Willers ◽

Dorothee Viemann

Keyword(s):

Gut Microbiota ◽

Host Defense ◽

Gut Microbiome ◽

Respiratory Infections ◽

Current Knowledge ◽

Viral Pathogens ◽

Commensal Microbiota ◽

Enhanced Resistance ◽

The Impact

Abstract Colonization of the intestine with commensal bacteria is known to play a major role in the maintenance of human health. An altered gut microbiome is associated with various ensuing diseases including respiratory diseases. Here, we summarize current knowledge on the impact of the gut microbiota on airway immunity with a focus on consequences for the host defense against respiratory infections. Specific gut commensal microbiota compositions and functions are depicted that mediate protection against respiratory infections with bacterial and viral pathogens. Lastly, we highlight factors that have imprinting effects on the establishment of the gut microbiota early in life and are potentially relevant in the context of respiratory infections. Deepening our understanding of these relationships will allow to exploit the knowledge on how gut microbiome maturation needs to be modulated to ensure lifelong enhanced resistance towards respiratory infections.

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Altered diversity and composition of gut microbiota in Wilson's disease

Scientific Reports ◽

10.1038/s41598-020-78988-7 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Xiangsheng Cai ◽

Lin Deng ◽

Xiaogui Ma ◽

Yusheng Guo ◽

Zhiting Feng ◽

...

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Wilson’S Disease ◽

Wilson's Disease ◽

Healthy Individuals ◽

Lower Abundance ◽

Rrna Sequencing ◽

Healthy Control ◽

The Impact ◽

Bacterial Groups

AbstractWilson’s disease (WD) is an autosomal recessive inherited disorder of chronic copper toxicosis with high mortality and disability. Recent evidence suggests a correlation between dysbiosis in gut microbiome and multiple diseases such as genetic and metabolic disease. However, the impact of intestinal microbiota polymorphism in WD have not been fully elaborated and need to be explore for seeking some microbiota benefit for WD patients. In this study, the 16S rRNA sequencing was performed on fecal samples from 14 patients with WD and was compared to the results from 16 healthy individuals. The diversity and composition of the gut microbiome in the WD group were significantly lower than those in healthy individuals. The WD group presented unique richness of Gemellaceae, Pseudomonadaceae and Spirochaetaceae at family level, which were hardly detected in healthy controls. The WD group had a markedly lower abundance of Actinobacteria, Firmicutes and Verrucomicrobia, and a higher abundance of Bacteroidetes, Proteobacteria, Cyanobacteria and Fusobacteria than that in healthy individuals. The Firmicutes to Bacteroidetes ratio in the WD group was significantly lower than that of healthy control. In addition, the functional profile of the gut microbiome from WD patients showed a lower abundance of bacterial groups involved in the host immune and metabolism associated systems pathways such as transcription factors and ABC-type transporters, compared to healthy individuals. These results implied dysbiosis of gut microbiota may be influenced by the host metabolic disorders of WD, which may provide a new understanding of the pathogenesis and new possible therapeutic targets for WD.

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From the Table to the Tumor: The Role of Mediterranean and Western Dietary Patterns in Shifting Microbial-Mediated Signaling to Impact Breast Cancer Risk

Nutrients ◽

10.3390/nu11112565 ◽

2019 ◽

Vol 11 (11) ◽

pp. 2565 ◽

Cited By ~ 8

Author(s):

Tiffany M. Newman ◽

Mara Z. Vitolins ◽

Katherine L. Cook

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Mediterranean Diet ◽

Dietary Patterns ◽

Gut Microbiome ◽

Western Diet ◽

Diet Pattern ◽

The Mediterranean ◽

The Impact

Diet is a modifiable component of lifestyle that could influence breast cancer development. The Mediterranean dietary pattern is considered one of the healthiest of all dietary patterns. Adherence to the Mediterranean diet protects against diabetes, cardiovascular disease, and cancer. Reported consumption of a Mediterranean diet pattern was associated with lower breast cancer risk for women with all subtypes of breast cancer, and a Western diet pattern was associated with greater risk. In this review, we contrast the available epidemiological breast cancer data, comparing the impact of consuming a Mediterranean diet to the Western diet. Furthermore, we will review the preclinical data highlighting the anticancer molecular mechanism of Mediterranean diet consumption in both cancer prevention and therapeutic outcomes. Diet composition is a major constituent shaping the gut microbiome. Distinct patterns of gut microbiota composition are associated with the habitual consumption of animal fats, high-fiber diets, and vegetable-based diets. We will review the impact of Mediterranean diet on the gut microbiome and inflammation. Outside of the gut, we recently demonstrated that Mediterranean diet consumption led to distinct microbiota shifts in the mammary gland tissue, suggesting possible anticancer effects by diet on breast-specific microbiome. Taken together, these data support the anti-breast-cancer impact of Mediterranean diet consumption.

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Gut Microbiome Modulation Based on Probiotic Application for Anti-Obesity: A Review on Efficacy and Validation

Microorganisms ◽

10.3390/microorganisms7100456 ◽

2019 ◽

Vol 7 (10) ◽

pp. 456 ◽

Cited By ~ 9

Author(s):

Kaliyan Barathikannan ◽

Ramachandran Chelliah ◽

Momna Rubab ◽

Eric Banan-Mwine Daliri ◽

Fazle Elahi ◽

...

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Molecular Mechanisms ◽

Short Chain Fatty Acids ◽

Genetic Profile ◽

Fecal Transplantation ◽

Intestinal Microbes ◽

Prevalence Of Obesity ◽

Future Direction ◽

The Impact

The growing prevalence of obesity has become an important problem worldwide as obesity has several health risks. Notably, factors such as excessive food consumption, a sedentary way of life, high sugar consumption, a fat-rich diet, and a certain genetic profile may lead to obesity. The present review brings together recent advances regarding the significance of interventions involving intestinal gut bacteria and host metabolic phenotypes. We assess important biological molecular mechanisms underlying the impact of gut microbiota on hosts including bile salt metabolism, short-chain fatty acids, and metabolic endotoxemia. Some previous studies have shown a link between microbiota and obesity, and associated disease reports have been documented. Thus, this review focuses on obesity and gut microbiota interactions and further develops the mechanism of the gut microbiome approach related to human obesity. Specifically, we highlight several alternative diet treatments including dietary changes and supplementation with probiotics. The future direction or comparative significance of fecal transplantation, synbiotics, and metabolomics as an approach to the modulation of intestinal microbes is also discussed.

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11β-hydroxysteroid dehydrogenase-1 deficiency alters the gut microbiome response to Western diet

Journal of Endocrinology ◽

10.1530/joe-16-0578 ◽

2017 ◽

Vol 232 (2) ◽

pp. 273-283 ◽

Cited By ~ 4

Author(s):

Jethro S Johnson ◽

Monica N Opiyo ◽

Marian Thomson ◽

Karim Gharbi ◽

Jonathan R Seckl ◽

...

Keyword(s):

Relative Abundance ◽

Gut Microbiome ◽

Inflammatory Responses ◽

Hydroxysteroid Dehydrogenase ◽

Western Diet ◽

Metabolic Effects ◽

Chow Diet ◽

The Family ◽

The Impact

The enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD) interconverts active glucocorticoids and their intrinsically inert 11-keto forms. The type 1 isozyme, 11β-HSD1, predominantly reactivates glucocorticoids in vivo and can also metabolise bile acids. 11β-HSD1-deficient mice show altered inflammatory responses and are protected against the adverse metabolic effects of a high-fat diet. However, the impact of 11β-HSD1 on the composition of the gut microbiome has not previously been investigated. We used high-throughput 16S rDNA amplicon sequencing to characterise the gut microbiome of 11β-HSD1-deficient and C57Bl/6 control mice, fed either a standard chow diet or a cholesterol- and fat-enriched ‘Western’ diet. 11β-HSD1 deficiency significantly altered the composition of the gut microbiome, and did so in a diet-specific manner. On a Western diet, 11β-HSD1 deficiency increased the relative abundance of the family Bacteroidaceae, and on a chow diet, it altered relative abundance of the family Prevotellaceae. Our results demonstrate that (i) genetic effects on host–microbiome interactions can depend upon diet and (ii) that alterations in the composition of the gut microbiome may contribute to the aspects of the metabolic and/or inflammatory phenotype observed with 11β-HSD1 deficiency.

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