Gut microbiota varies by opioid use, circulating leptin and oxytocin in African American men with diabetes and high burden of chronic disease

Barengolts, Elena; Green, Stefan J.; Eisenberg, Yuval; Akbar, Arfana; Reddivari, Bharathi; Layden, Brian T.; Dugas, Lara R.; Chlipala, George E.

doi:10.1371/journal.pone.0194171

Cited by 80 publications

(74 citation statements)

References 51 publications

(119 reference statements)

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“…Within Firmicutes, ob/ob mice had lower relative abundances of Clostridium and Lactobacillus compared to control Het mice. In support, high leptin levels associate with Lactobacillales, the order containing Lactobacillus spp., in African-American men [88]. Most Lactobacilli spp.…”

Section: Discussionmentioning

confidence: 99%

Estradiol modulates gut microbiota in femaleob/obmice fed a high fat diet

Gao

et al. 2019

Preprint

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0Estrogens protect against diet-induced obesity in women and female rodents. In support of these 2 1 anorectic effects, lack of estrogens in postmenopausal women is associated with weight gain, 2 2 increasing their risk for cardiovascular diseases and cancer. Estrogens act with leptin, a satiety 2 3 2 hormone encoded by the ob gene, to regulate energy homeostasis in females. Leptin-deficient 1 mice (ob/ob) exhibit morbid obesity and insulin resistance. In addition to estrogens and leptin, 2 the gut microbiome (gut microbes and their metabolites), is critical in regulating energy 3 metabolism. The present study investigates whether estrogens and leptin modulate gut 4 microbiota in ovariectomized ob/ob (obese) or heterozygote (lean) control mice fed a high-fat 5 diet (HFD) that received either 17β-Estradiol (E2) or vehicle implants. E2 attenuated weight gain 6 in both genotypes compared to vehicle counterparts. Moreover, both obesity (ob/ob mice) and 7 E2 reduced gut microbial diversity. ob/ob mice exhibited lower species richness than control 8 mice, while E2-treated mice had reduced evenness compared to vehicle mice. Regarding taxa, 9 E2 treatment was associated with higher abundances of the family S24-7. Leptin was associated targeting the gut microbiome for hormone-dependent metabolic disorders in women. 1 6 1 7 1 8 1 9 2 1and behavior [4][5][6]. Estrogens reduce food intake, attenuate body weight gain and adiposity, and 2 2 increase physical activity in both humans and rodents [1, 2]. Postmenopausal women have lower 2 3 3 levels of circulating estrogens and an increased tendency to gain fat weight, which increases their 1 risk for obesity, cardiovascular disease, stroke, and type 2 diabetes [7][8][9]. Similarly, in mice on a 2 high-fat diet (HFD), ovariectomy increases energy intake and the development of obesity, while 3 estradiol (E2) treatment prevents weight gain [2,[10][11][12][13], indicating that estrogens protect against 4 HFD-induced obesity. 6Leptin is a peptide hormone secreted primarily by adipocytes, which acts in the brain to stimulate 7 metabolism, promote satiety, and regulate fat storage [14][15][16]. A mutation in the ob gene that 8 encodes leptin results in mice lacking the hormone (ob/ob) [17]. While phenotypically normal at 9 birth, ob/ob mice quickly develop obesity and diabetes [18]. Additionally, ob/ob mice exhibit 1 0 increased food intake and decreased physical activity, energy metabolism, and body temperature 1 1 compared to lean controls, making ob/ob mice an excellent genetic model of obesity [19][20][21]. 2Administering leptin to adult ob/ob mice reverses these effects by decreasing food intake, 1 3 increasing energy output and decreasing circulating levels of glucose and insulin [22, 23]. 1 4 1 5Leptin and estrogen signaling pathways interact to influence reproduction and energy 1 6 metabolism. High levels of E2 are associated with increased leptin sensitivity in both male and 1 7 female rodents [24]. In mice, ovariectomy decreases leptin sensitivity, but can be restored by E2 1 ...

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Section: Discussionmentioning

confidence: 99%

Estradiol modulates gut microbiota in femaleob/obmice fed a high fat diet

Gao

et al. 2019

Preprint

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“…The current analysis was performed as a sub-analysis in the cross-sectional study of Glucose Tolerance and Vitamin D insu ciency in African American Men (AAM), investigating glucose metabolism and selected biomarker interactions in AAM [42,43]. The original study was conducted at an urban Veteran Administration Medical Center (VAMC).…”

Section: Design and Participantsmentioning

confidence: 99%

“…The original study was conducted at an urban Veteran Administration Medical Center (VAMC). The intended subject populations (N=100) included those with T2D (N=50) and those without T2D (normal glucose tolerance participants, N=50) [42,43]. The inclusion criteria were glycohemoglobin HbA1c < 5.7% for NGT or 6.5-7.4% for T2D, age 35-70 years, body mass index (BMI) 22-39.9 kg/m 2 , and 25OH-vitamin D (25OHD) < 30 ng/ml.…”

Section: Design and Participantsmentioning

confidence: 99%

“…The research staff reviewed past medical history and medication use. The OGTT using 75 g glucose load was performed and blood was collected for biomarker analysis as previously described [42,43]. For this pilot study blood samples for analysis of adipocytokines, were chosen at random based on availability of samples at 0-and 120-minute of OGTT.…”

Section: Design and Participantsmentioning

confidence: 99%

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Predictors of HbA1c among adipocytokine biomarkers in African American men with varied glucose tolerance

Barengolts¹,

Akbar

Layden

et al. 2020

Preprint

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Background: Adipocytokines are important in type 2 diabetes (T2D). This study explored adipocytokine associations with acute and chronic hyperglycemia in African American Men (AAM). Methods: Fourteen adipocytokines were measured (multiplex assay) in blood samples from men with normal glucose tolerance (NGT) or T2D (drug-naïve MF(-) or using metformin MF(+)). Acute and chronic hyperglycemia were evaluated at 120-minute of OGTT and by HbA1c, respectively. Results: AAM with T2D (N=21) compared to NGT (N=20) were significantly older (59 vs. 54 years) and had higher body mass index (BMI 35 vs. 27 kg/m2) (p<0.01 for both). Fasting and 120-minute OGTT glucose and insulin were higher in T2D than NGT, however, differences did not reach statistical significance after adjusting for age and BMI. In the fasted state, TNF-a, IL-6, PAI-1 (p<0.01 for all) and IL-13, adiponectin, adipsin, lipocalin (p<0.05 for all) were lower in T2D compared to NGT. At 120-minute post-glucose load (acute hyperglycemia) TNF-a, IL-6, IL-13, IL-8, PAI-1, adiponectin, adipsin (p<0.01 for all) and lipocalin, resistin (p<0.05 for both) were lower in T2D than in NGT group. There were no statistical differences for the other adipocytokines including GM-CSF, IL-7, IL-10, IP-10, and MCP-1. Regression analysis (adjusted for age and BMI) showed that fasting IL-8, TNF-a, adiponectin, lipocalin, resistin, adipsin, and PAI-1 were all associated with HbA1c (p<0.05 for all). Further modeling revealed that after adjusting for age, BMI, glucose tolerance status and metformin use, only adipsin remained significantly associated with HbA1c (p=0.004). The model including adipsin, TNF-a, age, BMI, and group designation (i.e. NGT, MF(-), MF(+)) explained 86% of HbA1c variability. Conclusions: The study suggested that adipsin could be independently associated with HbA1c in AAM with varied glucose tolerance. Additional studies should corroborate these data and provide mechanistic insights for enabling adipsin-related discoveries of novel T2D treatment.

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“…Opioids are known to affect the delay in gastric emptying and slow the intestinal movements which result in increased nausea and vomiting as well as constipation. Opioids are also known to change the bacterial content of the large bowel [40]. In patients addicted to opioids, there is a remarkable deficit of Bifidus and Prevotella sp.…”

Section: Gastrointestinal Disordersmentioning

confidence: 99%

Undiscovered morphine. The effects of the long-term use of the opioids

Żylicz

2019

Palliat Med Pract

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Morphine and other opioids are used much more often and for a longer time than before. This causes many relatively unknown adverse effects, which become apparent only after a while. One of them is opioid-induced hyperalgesia and abnormal magnesium metabolism. The adverse effect that negatively influences the quality of life is opioid-induced hypogonadism. Morphine can have a profound immunosuppressive and tumour-promoting effect. It is probably responsible for the increased rate of heart infarctions. Very interesting are suggestions that morphine and other opioids are changing the large bowel microbiome. All of these phenomena do not concern only few patients but are generalized in this population and the severity of the phenomenon depends only on the treatment period. Jet none of these adverse effects are mentioned in drug leaflets. All of these phenomena are treatable providing that the diagnose is made accurately and timely. It is very well possible that in the future we shall be able to prevent most of these adverse effects. Med Pract 2019; 13, 1: 22-26 Palliat

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Gut microbiota varies by opioid use, circulating leptin and oxytocin in African American men with diabetes and high burden of chronic disease

Cited by 80 publications

References 51 publications

Estradiol modulates gut microbiota in femaleob/obmice fed a high fat diet

Estradiol modulates gut microbiota in femaleob/obmice fed a high fat diet

Predictors of HbA1c among adipocytokine biomarkers in African American men with varied glucose tolerance

Undiscovered morphine. The effects of the long-term use of the opioids

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