Association Of Peripheral 5-Hydroxyindole-3-Acetic Acid, A Serotonin Derivative, with Metabolic Syndrome and Low-Grade Inflammation

Afarideh, Mohsen; Behdadnia, Aram; Noshad, Sina; Mirmiranpour, Hossein; Mousavizadeh, Mostafa; Khajeh, Elias; Rad, Mona Vahidi; Mazaheri, Tina; Nakhjavani, Manouchehr; Esteghamati, Alireza

doi:10.4158/ep14442.or

Cited by 20 publications

(15 citation statements)

References 39 publications

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“…Nevertheless, cross-sectional investigations in older adults are in line with our findings. These include an inverse association of tryptophan 48 and xanthurenic acid with CRP 49 , and a direct association between 5-hydroxyindole-3-acetic acid and CRP 50 . Other studies in adults that contrast our findings include lack of association of isoleucine 35 , lack of association of methionine and tryptophan 50 , and positive relation of isoleucine 51,52 with CRP.…”

Section: Discussionmentioning

confidence: 99%

“…These include an inverse association of tryptophan 48 and xanthurenic acid with CRP 49 , and a direct association between 5-hydroxyindole-3-acetic acid and CRP 50 . Other studies in adults that contrast our findings include lack of association of isoleucine 35 , lack of association of methionine and tryptophan 50 , and positive relation of isoleucine 51,52 with CRP. Although no study have reported an association between indole-3-carboxaldehyde and CRP; exogenous administration of indole-3-carboxaldehyde decreased the production of several inflammatory cytokines 53 .…”

Section: Discussionmentioning

confidence: 99%

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Longitudinal relationship of amino acids and indole metabolites with long-term body mass index and cardiometabolic risk markers in young individuals

Oluwagbemigun

Anesi

Ulaszewska

et al. 2020

Sci Rep

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Amino acid metabolites in biofluids are associated with high body mass index (BMI) and cardiometabolic abnormalities. However, prospective investigations regarding these associations are few, particularly among young individuals. Moreover, little is presently known about the impact of long-term high BMI. Using data from the DOrtmund Nutritional and Anthropometric Longitudinally Designed study (111 males and 107 females), we prospectively investigated relations between repeatedly measured urinary levels of 33 metabolites and (1) previously identified long-term BMI trajectory groups from childhood into late adolescence and (2) cardiometabolic risk markers in late adolescence-young adulthood, in sex-specific linear mixed regression models. Males with long-term overweight had lower indole-3-acetic acid when compared to others. Further, methionine, isoleucine, tryptophan, xanthurenic acid, and indole-3-carboxaldehyde were negatively associated with C-reactive protein (CRP), but 5-hydroxyindole-3-acetic acid was positively associated with CRP. No associations were observed in females. Long-term overweight from childhood into late adolescence is associated with decreased urinary levels of gut bacteria-derived indole-3-acetic acid, and several urinary amino acids, including gut bacteria-derived indole-3-carboxaldehyde are associated with elevated CRP later on in life. taken together, our data suggest that indole metabolites, and their gut bacteria producers play potentially important roles in overweight-related inflammation. High body mass index (BMI) during childhood and adolescence is still a major public health concern 1,2. The condition contributes to the development of cardiometabolic abnormalities such as inflammation over the life course 3. Dysregulated metabolism is one of the biological mechanisms through which high BMI contributes to the development of these cardiometabolic abnormalities 4,5. Scientific efforts have focused on carbohydrate and lipid metabolic perturbations as one of these mechanisms, interest in the impact of unfavorable alterations in protein/amino acid metabolism is now emerging 6,7. Therefore, it would be necessary to explore the link of high BMI, amino acid metabolites, and cardiometabolic abnormalities.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Longitudinal relationship of amino acids and indole metabolites with long-term body mass index and cardiometabolic risk markers in young individuals

Oluwagbemigun

Anesi

Ulaszewska

et al. 2020

Sci Rep

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“…Mounting evidence indicates that peripheral 5-HT production and bioavailability is increased in obesity. Expression of TPH1 [23,24] and PAX4 (a critical transcription factor in EC cell specification) [23] is augmented in the duodenum and gastric antrum of obese subjects, while levels of plasma 5-HT and serum levels of the 5-HT metabolite, 5-HIAA, are associated with measures of human obesity [24,34]. Rodent models of obesity also show increased EC cell density (per unit area) and 5-HT content, which precedes obesity, as well as augmented plasma 5-HT [21,22,23].…”

Section: Discussionmentioning

confidence: 99%

Sugar Responses of Human Enterochromaffin Cells Depend on Gut Region, Sex, and Body Mass

et al. 2019

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Gut-derived serotonin (5-HT) is released from enterochromaffin (EC) cells in response to nutrient cues, and acts to slow gastric emptying and modulate gastric motility. Rodent studies also evidence a role for gut-derived 5-HT in the control of hepatic glucose production, lipolysis and thermogenesis, and in mediating diet-induced obesity. EC cell number and 5-HT content is increased in the small intestine of obese rodents and human, however, it is unknown whether EC cells respond directly to glucose in humans, and whether their capacity to release 5-HT is perturbed in obesity. We therefore investigated 5-HT release from human duodenal and colonic EC cells in response to glucose, sucrose, fructose and α-glucoside (αMG) in relation to body mass index (BMI). EC cells released 5-HT only in response to 100 and 300 mM glucose (duodenum) and 300 mM glucose (colon), independently of osmolarity. Duodenal, but not colonic, EC cells also released 5-HT in response to sucrose and αMG, but did not respond to fructose. 5-HT content was similar in all EC cells in males, and colonic EC cells in females, but 3 to 4-fold higher in duodenal EC cells from overweight females (p < 0.05 compared to lean, obese). Glucose-evoked 5-HT release was 3-fold higher in the duodenum of overweight females (p < 0.05, compared to obese), but absent here in overweight males. Our data demonstrate that primary human EC cells respond directly to dietary glucose cues, with regional differences in selectivity for other sugars. Augmented glucose-evoked 5-HT release from duodenal EC is a feature of overweight females, and may be an early determinant of obesity.

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“…The increased PGG2 can increase pro-inflammatory macrophage activation induced by LPS in vitro (Alhouayek et al, 2013). The concentration of 5-HIAA was reported to be associated with highly sensitive C-reactive protein, which was a marker of chronic low-grade inflammation in metabolic syndrome (Afarideh et al, 2015). Hence, the presence of these pro-inflammatory substances may explain the aggravation of inflammation and even death in mice injected with the Supernatant 1.…”

Section: Research Articlementioning

confidence: 98%

Washed microbiota transplantation vs. manual fecal microbiota transplantation: clinical findings, animal studies and in vitro screening

Zhang

Zhao³

et al. 2020

Protein Cell

182

178

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Fecal microbiota transplantation (FMT) by manual preparation has been applied to treat diseases for thousands of years. However, this method still endures safety risks and challenges the psychological endurance and acceptance of doctors, patients and donors. Population evidence showed the washed microbiota preparation with microfiltration based on an automatic purification system followed by repeated centrifugation plus suspension for three times significantly reduced FMT-related adverse events. This washing preparation makes delivering a precise dose of the enriched microbiota feasible, instead of using the weight of stool. Intraperitoneal injection in mice with the fecal microbiota supernatant obtained after repeated centrifugation plus suspension for three times induced less toxic reaction than that by the first centrifugation following the microfiltration. The toxic reactions that include death, the change in the level of peripheral white blood cells, and the proliferation of germinal center in secondary lymphoid follicles in spleen were noted. The metagenomic next-generation sequencing (NGS) indicated the increasing types and amount of viruses could be washed out during the washing process. Metabolomics analysis indicated metabolites with pro-inflammatory effects in the fecal microbiota supernatant such as leukotriene B4, corticosterone, and prostaglandin G2 could be removed by repeated washing. Near-infrared absorption spectroscopy could be served as a rapid detection method to control the quality of the washingprocess. In conclusion, this study for the first time provides evidence linking clinical findings and animal experiments to support that washed microbiota transplantation (WMT) is safer, more precise and more quality-controllable than the crude FMT by manual.

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Association Of Peripheral 5-Hydroxyindole-3-Acetic Acid, A Serotonin Derivative, with Metabolic Syndrome and Low-Grade Inflammation

Cited by 20 publications

References 39 publications

Longitudinal relationship of amino acids and indole metabolites with long-term body mass index and cardiometabolic risk markers in young individuals

Longitudinal relationship of amino acids and indole metabolites with long-term body mass index and cardiometabolic risk markers in young individuals

Sugar Responses of Human Enterochromaffin Cells Depend on Gut Region, Sex, and Body Mass

Washed microbiota transplantation vs. manual fecal microbiota transplantation: clinical findings, animal studies and in vitro screening

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