More Flavor for Flavonoid-Based Interventions?

doi:10.1016/j.molmed.2017.02.008

Trends in Molecular Medicine

Volume 23, Issue 4, April 2017, Pages 293-295

https://doi.org/10.1016/j.molmed.2017.02.008 Get rights and content

Poor diets are associated with obesity and a decline in cognitive function. Flavonoids are plant compounds that have been associated with improved metabolic parameters in obesity and reversal of cognitive decline. Given that microbial flavonoid conversion is important for bioactivity, flavonoid-derived neuroactive compounds may be functionally crucial in the gut microbiome–brain axis.

Section snippets

Flavonoids: Secondary Plant and Fungi Metabolites

Flavonoids and isoflavonoids, secondary plant and fungi metabolites commonly occurring as glycosides in nature, comprise a range of related compounds such as anthoxanthins (flavones and flavonols), flavanones, flavononols, flavans (e.g., flavan-3-ols and flavan-4-ols), anthocyanidins, isoflavones, and isoflavanes, among others. To date, those identified in food products fall into six categories: anthocyanidins, flavan-3-ols, flavones, flavonols, flavonones, and isoflavones [1]. These exhibit

Flavonoids, Gut Microbiome, and Metabolic Parameters of Obesity

Once ingested, flavonoids can modulate the composition of the gut microbiota not only through antimicrobial activities but also by becoming nutrient sources for particular bacterial species. Extensive findings show benefits of these plant-derived compounds in humans and animals, with flavonoid supplementation being among the most effective dietary interventions for weight loss. For example, a cranberry extract high in flavonols, anthocyanins, and proanthocyanidins (oligomeric flavonoids) given

Flavonoids, Gut Microbiome, Obesity, and Cognitive Function

From a different perspective, the influence of the gut microbiota on brain function through the gut–brain axis has garnered significant interest in recent years. Obesogenic diets have been reported to negatively impact on cognitive performance 7, 8 (Figure 1). For example, mice receiving a fecal matter transplant of microbiota shaped by a HFD have shown disruptions in cognitive behavioral tests (e.g., memory measurements using fear conditioning) compared to those transplanted with control

The Gut Microbiome and Extra-Gastrointestinal Effects of Flavonoid-Derived Metabolites

From these findings, another thought-provoking research question emerges. Could gut microbial modulation of intestinal flavonoid levels contribute to a cognitive decline associated with obesogenic diets? Indeed, evidence supports a microbial role in the extra-gastrointestinal effects of flavonoid-derived compounds; in a recent double-blind, placebo-controlled crossover clinical trial the authors examined the acute vascular benefits of soy consumption in healthy human males [14]. Soy contains

Concluding Remarks

Given these novel and exciting findings, and the considerable interest in the prebiotic potential of flavonoids, the challenge now will be to confirm if flavonoids are crucial to the gut microbiome–brain axis in obesity and beyond (Figure 1). The extensive repertoire of naturally available flavonoids (over 8000 different flavonoid compounds are known [1]), and the potential for metabolic engineering of flavonoid biosynthesis, provide novel opportunities to offset the effects of poor diets. In

Acknowledgments

N.O.K. is supported by a Cancer Institute NSW Career Development Fellowship (15/CDF/1-11). M.J.M. acknowledges funding from the National Health and Medical Research Council, Australia.

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Obese-type gut microbiota induce neurobehavioral changes in the absence of obesity
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J.E. Beilharz
The effect of short-term exposure to energy-matched diets enriched in fat or sugar on memory, gut microbiota and markers of brain inflammation and plasticity
Brain Behav. Immun.
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Y. Liu
Luteolin protects against high fat diet-induced cognitive deficits in obesity mice
Behav. Brain Res.
(2014)
R.W. Johnson
Feeding the beast: can microglia in the senescent brain be regulated by diet?
Brain Behav. Immun.
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S. Hazim
Acute benefits of the microbial-derived isoflavone metabolite equol on arterial stiffness in men prospectively recruited according to equol producer phenotype: a double-blind randomized controlled trial
Am. J. Clin. Nutr.
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A. Braune et al.
Bacterial species involved in the conversion of dietary flavonoids in the human gut
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Complex C-glycosyl flavonoid phytoalexins from Cucumis sativus
J. Nat. Prod.
(2003)

There are more references available in the full text version of this article.

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Tomato fruit consumption is influenced by flavor and nutrient quality. In the present study, we investigate the impact of water saving irrigation (WSI) as a pre-harvest management on flavor and nutrient quality of tomato fruit. Our results demonstrate that WSI-treated tomato fruit exhibited improved sensory scores as assessed by a taste panel, accompanied by elevated levels of SlGLK2 expression, sugars, acids, and carotenoid contents compared to non-treated fruit. Notably, WSI treatment significantly enhanced the development of chloroplast and plastoglobulus in chromoplast, which served as carotenoid storage sites and upregulated the expression of carotenoid biosynthetic genes. Furthermore, integrated transcriptome and metabolome analysis revealed heightened expression of sugar and flavonoid metabolism pathways in WSI-treated tomato fruit. Remarkably, the master regulator SlMYB12 displayed a substantially increased expression due to WSI. These findings suggest that WSI is an effective and sustainable approach to enhance the pigments metabolism and storage capacity as well as the organoleptic characteristics and nutritional value of tomato fruit, offering a win-win solution for both water conservation and quality improvement in agro-food production.
Integrated metabolomics and transcriptomics reveals difference involved in flavonoid and indole alkaloids biosynthesis in potato tuber flesh
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Colored potatoes have garnered attention due to their higher nutrients compared to regular potatoes. This study describes a combined transcriptomic and metabolomic analysis of potato tubers originating from a single sexual cross between two parents with differing tuber skin and flesh colors. Through the use of RNA-seq, and UPLC-MS/MS metabolomics, this study aimed to elucidate the genetic and metabolic variations involved in the transmission of traits from tetraploid potato parents to hybrid F₁ offspring. Our analysis revealed unique genes and metabolites associated with flavonoids and alkaloids within each group of offspring. Phenolic acids, flavonoids, and alkaloids are highlighted as key contributors to the positive heterosis observed in the tubers of potato hybrids, as assessed by calculating mid-parent heterosis for metabolites in three potato hybrids. At the overall metabolites level, hybrid SB (red-skinned and red-fleshed) exhibited a higher mid-parent heterosis than hybrid SA (purple-skinned and purple-fleshed) and SC (yellow-skinned and yellow-fleshed). Within hybrid SB tuber, specific accumulations of luteolin, salicin, isovitexin, and esculeoside B-5 were identified. Moreover, co-expression networks and correlation analysis pinpoint genes related to flavonoid and alkaloid biosynthesis. Notably, StDFR (dihydroflavonol reductase), a gene involved in flavonoid synthesis in potato tuber flesh, exhibits heightened expression in colored potato flesh. Additionally, we identified StYUCCA (indole-3-pyruvate monooxygenase), a gene regulating indole alkaloids synthesis, with elevated expression in yellow potato flesh. These findings provide insights into the utilization of heterosis breeding and the regulation of genes-metabolites in colored potato tuber flesh.
Subchronic exposure to PM<inf>2.5</inf> induced renal function damage and intestinal microflora changes in rats
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Exposure to inhalable environmental particulate matter with a diameter of 2.5 µm or smaller (PM_2.5) is associated with decreased or impaired kidney function, but the underlying biological mechanisms are not fully understood. Gut microbiota is an emerging key player in the homeostasis regulation of the gut-kidney axis. Few studies have investigated its role in PM_2.5 exposure-induced gut-kidney axis homeostasis abnormalities.
In this study, a versatile aerosol concentration enrichment system for medium- to long-term whole-body exposure was used to expose Sprague-Dawley rats to filtered air (FA) or concentrated ambient PM_2.5 for 12 weeks. A correlation analysis of renal impairment and the intestinal microbiome was performed.
The urine flow rate calculation and renal function analysis showed that PM_2.5 exposure significantly impaired renal function and increased the urine flow rate. The fecal microbiota analysis showed that renal impairment and increased urine flow rates were consistent with the reduced estimates of the fecal bacteria Chao1, observed-species, Shannon, and Simpson (richness and diversity indices). Pearson’s correlation analysis showed that the estimated bacterial richness and diversity were correlated with the urine flow rate and renal function. The linear discriminant analysis effect size (LEfSe) analysis revealed differences between animals exposed to PM_2.5 and FA in 25 bacterial groups. Further correlation of a single bacterial taxon with the urine flow rate and renal function showed that the relative abundances of 30, 29, 21, and 50 distinct bacterial groups were significantly correlated with the urine flow rate, estimated glomerular filtration rate (eGFR), serum cystatin C (CysC), and beta-2 microglobulin (β2-MG), respectively.
Subchronic exposure to PM_2.5 can cause intestinal ecological disorders, which may, in turn, lead to decreased kidney function or the development of impaired kidney function.
Enzymatic glucosylation of citrus flavonoids to enhance their bioactivity and taste as new food additives
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Citation Excerpt :
Many studies showed that citrus flavonoids could act as antioxidants and have good antioxidant effects in the prevention of cancer, cardiovascular diseases, gastric ulcers, allergies and even antibacterial infections [3–5]. Some citrus flavonoids are able to improve the flavor of foods and beverages because the compounds have de-bittering or sweetening property and can be used as natural flavorings, such as those utilizing in alcohol, jam, natural food additives and health care products [6]. In recent years, citrus flavonoids have attracted great attention from food industry because the natural food additives are high-valued.
Cyclodextrin glucosyltransferase (CGTase) is commonly used to produce cyclodextrins but its utility in flavonoids modification is rarely found. In the present study, an enzymatic transformation of citrus flavonoids by applying CGTase as the catalyst was investigated to produce a number of novel polyglucosylated derivatives from monoglucoside metabolites of citrus flavonoid diglycosides. Under the optimized conditions, the yield of glucosylated products achieved 80%. The water solubility and water partition coefficient of citrus flavonoids before and after the structural modification were compared. The results revealed that the water solubility of the flavonoids modified by glucosylation was significantly increased while the oil-water partition coefficient was just slightly reduced. Moreover, after glucosylation, the products have good anti-inflammatory and antioxidant effects. Interestingly, the taste property (bitterness and sweetness) of the glucosylated products was ameliorated. An evaluation with a Taste-Sensing System showed that the taste of the glucosylated products was strongly correlated with the attached rhamnosyl group (bitter taste) and glucosyl group (sweet taste), indicating that the amelioration of taste of flavonoids could be mainly attributed to the addition of glycosyl groups. The present study demonstrated a novel molecular engineering approach for the enhancement of water solubility and amelioration of taste for some citrus flavonoids, which may have potential applications in the functional food industry.
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Citation Excerpt :
Fig. 5F). The abundance of the family of Ruminococcaceae was increased in obese patients whose diet was rich in saturated fats and simple sugars as well as in patients with irritable bowel syndrome [42,43]. The relative abundance of Anaerotruncus was found to be casually correlated with obesity and its associated metabolic disorders in early studies [44,45].
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Citation Excerpt :
These secondary metabolites are ubiquitous in plants and have tremendous chemical diversity, as well as varied roles (Jin et al., 2000; Sheehan et al., 2015; Grotewold, 2016; Tohge et al., 2016). In addition, flavonoids are reported to benefit health by having anti-cancer, antioxidant, and anti-osteoporotic activities (Echeverry et al., 2015; Kaakoush and Morris, 2017). As well as the health benefits of compounds such as flavonoids, many recent studies have focused on the regulation of plant defense compounds such as steroidal glycoalkaloids (SGAs).
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Trends in Molecular Medicine

Section snippets

Flavonoids: Secondary Plant and Fungi Metabolites

Flavonoids, Gut Microbiome, and Metabolic Parameters of Obesity

Flavonoids, Gut Microbiome, Obesity, and Cognitive Function

The Gut Microbiome and Extra-Gastrointestinal Effects of Flavonoid-Derived Metabolites

Concluding Remarks

Acknowledgments

References (15)

Obese-type gut microbiota induce neurobehavioral changes in the absence of obesity

Biol. Psychiatry

The effect of short-term exposure to energy-matched diets enriched in fat or sugar on memory, gut microbiota and markers of brain inflammation and plasticity

Brain Behav. Immun.

Luteolin protects against high fat diet-induced cognitive deficits in obesity mice

Behav. Brain Res.

Feeding the beast: can microglia in the senescent brain be regulated by diet?

Brain Behav. Immun.

Acute benefits of the microbial-derived isoflavone metabolite equol on arterial stiffness in men prospectively recruited according to equol producer phenotype: a double-blind randomized controlled trial

Am. J. Clin. Nutr.

Bacterial species involved in the conversion of dietary flavonoids in the human gut

Gut Microbes

Complex C-glycosyl flavonoid phytoalexins from Cucumis sativus

J. Nat. Prod.

Cited by (23)

Water saving irrigation mediates bioactive pigments metabolism and storage capacity in tomato fruit

Integrated metabolomics and transcriptomics reveals difference involved in flavonoid and indole alkaloids biosynthesis in potato tuber flesh

Subchronic exposure to PM<inf>2.5</inf> induced renal function damage and intestinal microflora changes in rats

Enzymatic glucosylation of citrus flavonoids to enhance their bioactivity and taste as new food additives

Amelioration of metabolic disorders by a mushroom-derived polyphenols correlates with the reduction of Ruminococcaceae in gut of DIO mice

MicroTom Metabolic Network: Rewiring Tomato Metabolic Regulatory Network throughout the Growth Cycle

Trends in Molecular Medicine

ForumMore Flavor for Flavonoid-Based Interventions?

Section snippets

Flavonoids: Secondary Plant and Fungi Metabolites

Flavonoids, Gut Microbiome, and Metabolic Parameters of Obesity

Flavonoids, Gut Microbiome, Obesity, and Cognitive Function

The Gut Microbiome and Extra-Gastrointestinal Effects of Flavonoid-Derived Metabolites

Concluding Remarks

Acknowledgments

Biol. Psychiatry

Brain Behav. Immun.

Behav. Brain Res.

Brain Behav. Immun.

Am. J. Clin. Nutr.

Bacterial species involved in the conversion of dietary flavonoids in the human gut

Gut Microbes

Complex C-glycosyl flavonoid phytoalexins from Cucumis sativus

J. Nat. Prod.

Forum
More Flavor for Flavonoid-Based Interventions?