| 1. |
- Carvalho, Lucas Rannier Ribeiro Antonino, et al.
(författare)
-
Antibacterial mouthwash alters gut microbiome, reducing nutrient absorption and fat accumulation in Western diet-fed mice
- 2024
-
Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Prolonged use of antibacterial mouthwash is linked to an increased risk of systemic disease. We aimed to investigate if disturbing the oral microbiota would impact the lower gut microbiome with functional effects in diet-induced obesity. Mice were exposed to oral chlorhexidine and fed a Western diet (WD). Food intake and weight gain were monitored, and metabolic function, blood pressure, and microbiota were analyzed. Chlorhexidine reduced the number of viable bacteria in the mouth and lowered species richness in the gut but with proportional enrichment of some bacteria linked to metabolic pathways. In mice fed a Western diet, chlorhexidine reduced weight gain, body fat, steatosis, and plasma insulin without changing caloric intake, while increasing colon triglycerides and proteins, suggesting reduced absorption of these nutrients. The mechanisms behind these effects as well as the link between the oral microbiome and small intestinal function need to be pinpointed. While the short-term effects of chlorhexidine in this model appear beneficial, potential long-term disruptions in the oral and gut microbiota and possible malabsorption should be considered.
|
|
| 2. |
- du Toit, Lisa, et al.
(författare)
-
The Effect of Dietary Nitrate on the Oral Microbiome and Salivary Biomarkers in Individuals with High Blood Pressure.
- 2024
-
Ingår i: Journal of Nutrition. - : Elsevier. - 0022-3166 .- 1541-6100.
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Green leafy vegetables (GLV) contain inorganic nitrate, an anion with potential prebiotic effects on the oral microbiome. However, it remains unclear whether GLV and pharmacological supplementation [potassium nitrate (PN)] with a nitrate salt induce similar effects on the oral microbiome.OBJECTIVES: This study aimed to compare the effect of GLV with PN supplementation on the oral microbiome composition and salivary biomarkers in individuals with high blood pressure.METHODS: Seventy individuals were randomly allocated to 3 different groups to follow a 5-wk dietary intervention. Group 1 consumed 300 mg/d of nitrate in form of GLV. Group 2 consumed pills with 300 mg/d of PN and low-nitrate vegetables. Group 3 consumed pills with potassium chloride (placebo: PLAC) and low-nitrate vegetables. The oral microbiome composition and salivary biomarkers of oral health were analyzed before and after the dietary intervention.RESULTS: The GLV and PN groups showed similar microbial changes, probably nitrate-dependent, including an increase in the abundance of Neisseria, Capnocytophaga, Campylobacter species, and a decrease in Veillonella, Megasphaera, Actinomyces, and Eubacterium species after the treatment. Increased abundance of Rothia species, and reduced abundance of Streptococcus, Prevotella, Actinomyces, and Mogibacterium species were observed in the GLV group, which could be nitrate-independent. GLV and PN treatments increased salivary pH, but only GLV treatment showed an increase in the salivary buffering capacity and a reduction of lactate.CONCLUSION: The combination of nitrate-dependent and nitrate-independent microbial changes in the GLV group has a stronger effect to potentially improve oral health biomarkers compared with PN.
|
|
| 3. |
- Kleschyov, Andrei L., et al.
(författare)
-
NO-ferroheme is a signaling entity in the vasculature
- 2023
-
Ingår i: Nature Chemical Biology. - 1552-4450 .- 1552-4469. ; 19:10, s. 1267-1275
-
Tidskriftsartikel (refereegranskat)abstract
- Despite wide appreciation of the biological role of nitric oxide (NO) synthase (NOS) signaling, questions remain about the chemical nature of NOS-derived bioactivity. Here we show that NO-like bioactivity can be efficiently transduced by mobile NO-ferroheme species, which can transfer between proteins, partition into a hydrophobic phase and directly activate the sGC-cGMP-PKG pathway without intermediacy of free NO. The NO-ferroheme species (with or without a protein carrier) efficiently relax isolated blood vessels and induce hypotension in rodents, which is greatly potentiated after the blockade of NOS activity. While free NO-induced relaxations are abolished by an NO scavenger and in the presence of red blood cells or blood plasma, a model compound, NO-ferroheme-myoglobin preserves its vasoactivity suggesting the physiological relevance of NO-ferroheme species. We conclude that NO-ferroheme behaves as a signaling entity in the vasculature. Questions remain on the nature of the bioactivity of nitric oxide (NO) synthase signaling despite its wide appreciation. Here the authors describe NO-ferroheme as a vascular signaling species, whose biological activity is unrelated to the release of free nitric oxide, but allows it to travel protected to its main target guanylyl cyclase.
|
|
| 4. |
- Lundberg, Jon O, et al.
(författare)
-
The Tortoise and the Hare.
- 2023
-
Ingår i: Trends in endocrinology and metabolism. - : Elsevier. - 1043-2760 .- 1879-3061. ; 34:6, s. 317-318
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Distance running requires a high absolute oxygen consumption, while for a breath-hold diver the opposite is preferable. We compared physiological exercise parameters and mitochondrial function in a competitive triathlete with those seen in an accomplished breath-hold diver and notice some remarkable differences, possibly explaining why both have become successful.
|
|
| 5. |
- Moretti, Chiara H., et al.
(författare)
-
Dietary nitrite extends lifespan and prevents age-related locomotor decline in the fruit fly
- 2020
-
Ingår i: Free Radical Biology & Medicine. - : Elsevier BV. - 0891-5849 .- 1873-4596. ; 160, s. 860-870
-
Tidskriftsartikel (refereegranskat)abstract
- Aging is associated with decreased nitric oxide (NO) bioavailability and signalling. Boosting of a dietary nitrate nitrite-NO pathway e.g. by ingestion of leafy green vegetables, improves cardiometabolic function, mitochondrial efficiency and reduces oxidative stress in humans and rodents, making dietary nitrate and nitrite an appealing intervention to address age-related disorders. On the other hand, these anions have long been implicated in detrimental health effects of our diet, particularly in formation of carcinogenic nitrosamines.The aim of this study was to assess whether inorganic nitrite affects lifespan in Drosophila melanogaster and investigate possible mechanisms underlying any such effect.In a survival assay, female flies fed a nitrite supplemented diet showed lifespan extension by 9 and 15% with 0.1 and 1 mu M nitrite respectively, with no impact of nitrite on reproductive output. Interestingly, nitrite could also protect female flies from age-dependent locomotor decline, indicating a protective effect on healthspan. NO generation from nitrite involved Drosophila commensal bacteria and was indicated by a fluorescent probe as well as direct measurements of NO gas formation with chemiluminescence.Nutrient sensing pathways such as TOR and sirtuins, have been strongly implicated in lifespan extension. In aged flies, nitrite supplementation significantly downregulated dTOR and upregulated dSir2 gene expression. Total triglycerides and glucose were decreased, a described downstream effect of both TOR and sirtuin pathways.In conclusion, we demonstrate that very low doses of dietary nitrite extend lifespan and favour healthspan in female flies. We propose modulation of nutrient sensing pathways as driving mechanisms for such effects.
|
|
| 6. |
- Peng, Guotao, et al.
(författare)
-
Nitric oxide-dependent biodegradation of graphene oxide reduces inflammation in the gastrointestinal tract
- 2020
-
Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 12:32, s. 16730-16737
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding the biological fate of graphene-based materials such as graphene oxide (GO) is crucial to assess adverse effects following intentional or inadvertent exposure. Here we provide first evidence of biodegradation of GO in the gastrointestinal tract using zebrafish as a model. Raman mapping was deployed to assess biodegradation. The degradation was blocked upon knockdown ofnos2aencoding the inducible nitric oxide synthase (iNOS) or by pharmacological inhibition of NOS usingl-NAME, demonstrating that the process was nitric oxide (NO)-dependent. NO-dependent degradation of GO was further confirmedin vitroby combining a superoxide-generating system, xanthine/xanthine oxidase (X/XO), with an NO donor (PAPA NONOate), or by simultaneously producing superoxide and NO by decomposition of SIN-1. Finally, by using the transgenic strainTg(mpx:eGFP) to visualize the movement of neutrophils, we could show that inhibition of the degradation of GO resulted in increased neutrophil infiltration into the gastrointestinal tract, indicative of inflammation.
|
|
| 7. |
|
|
| 8. |
- Sundqvist, Michaela L, et al.
(författare)
-
A randomized clinical trial of the effects of leafy green vegetables and inorganic nitrate on blood pressure.
- 2020
-
Ingår i: American Journal of Clinical Nutrition. - : Oxford University Press. - 0002-9165 .- 1938-3207. ; 111:4, s. 749-756
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A diet rich in fruits and vegetables is associated with lowering of blood pressure (BP), but the nutrient(s) responsible for these effects remain unclear. Research suggests that inorganic nitrate present in leafy green vegetables is converted into NO in vivo to improve cardiovascular function.OBJECTIVE: In this study, we evaluated the effect of leafy green vegetables on BP in subjects with elevated BP, with the aim of elucidating if any such effect is related to their high nitrate content.DESIGN: We enrolled 243 subjects, 50-70 y old, with a clinic systolic BP (SBP) of 130-159 mm Hg. After a 2-wk run-in period on a nitrate-restricted diet the subjects were randomly assigned to receive 1 of the following 3 interventions daily for 5 wk: low-nitrate vegetables + placebo pills, low-nitrate vegetables + nitrate pills (300 mg nitrate), or leafy green vegetables containing 300 mg nitrate + placebo pills. The primary end point measure was the difference in change in 24 h ambulatory SBP between the groups.RESULTS: A total of 231 subjects (95%) completed the study. The insignificant change in ambulatory SBP (mean ± standard deviation) was -0.6 ± 6.2 mm Hg in the placebo group, -1.2 ± 6.8 mm Hg in the potassium nitrate group, and -0.5 ± 6.6 mm Hg in the leafy green vegetable group. There was no significant difference in change between the 3 groups.CONCLUSIONS: A 5-wk dietary supplementation with leafy green vegetables or pills containing the same amount of inorganic nitrate does not decrease ambulatory SBP in subjects with elevated BP. This trial was registered at clinicaltrials.gov as NCT02916615.
|
|
| 9. |
- Sundqvist, Michaela L, et al.
(författare)
-
Renal handling of nitrate in women and men with elevated blood pressure.
- 2021
-
Ingår i: Acta Physiologica. - : John Wiley & Sons. - 1748-1708 .- 1748-1716. ; 232:1
-
Tidskriftsartikel (refereegranskat)abstract
- AIM: The inorganic anions nitrate and nitrite are oxidation products of nitric oxide (NO) that have often been used as an index of NO generation. More than just being surrogate markers of NO, nitrate/nitrite can recycle to bioactive NO again. Nitrate is predominantly eliminated via the kidneys; however, there is less knowledge regarding tubular handling. The aim of this study, as part of a large randomized controlled trial, was to explore potential sex differences in renal nitrate handling during low and high dietary nitrate intake. We hypothesized that renal clearance and excretion of nitrate are higher in men compared to women.METHODS: In prehypertensive and hypertensive individuals (n = 231), nitrate and nitrite were measured in plasma and urine at low dietary nitrate intake (baseline) and after 5 weeks supplementation with nitrate (300 mg potassium nitrate/day) or placebo (300 mg potassium chloride/day). Twenty-four hours ambulatory blood pressure recordings and urine collections were conducted.RESULTS: At baseline, plasma nitrate and nitrite, as well as the downstream marker of NO signalling cyclic guanosine monophosphate, were similar in women and men. Approximately 80% of filtered nitrate was spared by the kidneys. Urinary nitrate concentration, amount of nitrate excreted, renal nitrate clearance (Cnitrate ) and fractional excretion of nitrate (FEnitrate ) were lower in women compared to men. No association was observed between plasma nitrate concentrations and glomerular filtration rate (GFR), nor between FEnitrate and GFR in either sex. After 5 weeks of nitrate supplementation plasma nitrate and nitrite increased significantly, but blood pressure remained unchanged. FEnitrate increased significantly and the sex difference observed at baseline disappeared.CONCLUSION: Our findings demonstrate substantial nitrate sparing capacity of the kidneys, which is higher in women compared to men. This suggests higher tubular nitrate reabsorption in women but the underlying mechanism(s) warrants further investigation.
|
|
| 10. |
- Yang, Jiangning, et al.
(författare)
-
Hypoxic erythrocytes mediate cardioprotection through activation of soluble guanylate cyclase and release of cyclic GMP
- 2023
-
Ingår i: Journal of Clinical Investigation. - : American Society For Clinical Investigation. - 0021-9738 .- 1558-8238. ; 133:17
-
Tidskriftsartikel (refereegranskat)abstract
- Red blood cells (RBCs) mediate cardioprotection via nitric oxide-like bioactivity, but the signaling and the identity of any mediator released by the RBCs remains unknown. We investigated whether RBCs exposed to hypoxia release a cardioprotective mediator and explored the nature of this mediator. Perfusion of isolated hearts subjected to ischemia-reperfusion with extracellular supernatant from mouse RBCs exposed to hypoxia resulted in improved postischemic cardiac function and reduced infarct size. Hypoxia increased extracellular export of cyclic guanosine monophosphate (cGMP) from mouse RBCs, and exogenous cGMP mimicked the cardioprotection induced by the supernatant. The protection induced by hypoxic RBCs was dependent on RBC-soluble guanylate cyclase and cGMP transport and was sensitive to phosphodiesterase 5 and activated cardiomyocyte protein kinase G. Oral administration of nitrate to mice to increase nitric oxide bioactivity further enhanced the cardioprotective effect of hypoxic RBCs. In a placebo-controlled clinical trial, a clear cardioprotective, soluble guanylate cyclase-dependent effect was induced by RBCs collected from patients randomized to 5 weeks nitrate-rich diet. It is concluded that RBCs generate and export cGMP as a response to hypoxia, mediating cardioprotection via a paracrine effect. This effect can be further augmented by a simple dietary intervention, suggesting preventive and therapeutic opportunities in ischemic heart disease.
|
|
