Quercetin and gut health -
YZ and A-YG revised and approved the final version. All authors contributed to the article and approved the submitted version. This work was supported by the National Key Research and Development Program of China YFA , and the National Natural Science Foundation of China Nos.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. ABX, antibiotic; DEGs, differentially expressed genes; HFD, high fat diet; LEfSe, linear discriminant analysis Effect Size; MSG, monosodium glutamate; NAFLD, non-alcoholic fatty liver disease; OTU, operational taxonomic units; PAS, periodic acid-schiff; PCoA, principal component analysis; PPAR-α, peroxisome proliferator-activated receptor-α; Que, quercetin; RetSat, retinol saturase.
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J Lipid Res. Other flavonoid-rich extracts include those from grapeseed, bilberry, Ginkgo biloba , and green tea. There are also water-soluble forms of quercetin available, such as hesperidin-methyl-chalcone HMC or quercetin-chalcone.
Quercetin is generally considered safe. Side effects may include headache and upset stomach. Preliminary evidence suggests that a byproduct of quercetin can lead to a loss of protein function.
Very high doses of quercetin may damage the kidneys. You should take periodic breaks from taking quercetin. If you are being treated with any of the following medications, you should not use quercetin supplements without talking to your health care provider first.
There is some concern that quercetin may reduce the effectiveness of certain antibiotics. Speak with your doctor. Quercetin may enhance the effect of these drugs, increasing your risk for bleeding. Anticoagulants include:. Test tube and animal studies suggest that quercetin may enhance the effects of doxorubicin and cisplatin, which are two chemotherapy medications used to treat cancer.
In addition, some doctors believe taking antioxidants at the same time as chemotherapy can be harmful, while others believe it can be helpful. In one study, combining quercetin with the anti-tumor drug doxorubicin, increased the drug's beneficial effects on breast cancer cells. In another, taking quercetin alongside cisplatin reduced the medicines' therapeutic effects in ovarian cancer cells.
Talk to your oncologist before taking any supplements if you are undergoing chemotherapy. Quercetin may interfere with the body's absorption of this drug, which is used to suppress the immune system.
Since quercetin affects the liver, concomitant use with medications that are changed by the liver may alter how the body metabolizes these medications. Speak with your physician.
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Monosodium glutamate MSG Hydrating night creams abdominal obesity, conventionally ehalth Quercetin and gut health hypothalamic damage, is a critical risk factor ahd health Queercetin. Microbiota-gut-brain axis plays important roles in Quercetin and gut health variety of metabolic diseases. However, whether gut microbiota is involved in the pathogenesis for MSG-induced abdominal obesity and the effect of quercetin on it remains unclear. Herein, we find that MSG-induced gut microbiota dysbiosis contributes to neuronal damage in the hypothalamus, as indicated by antibiotics-induced microbiota depletion and co-house treatment. Inspired by this finding, we investigate the mechanism in-depth for MSG-induced abdominal obesity.Quercetin and gut health -
Antifungals One of the more common causes of leaky gut has to do with an overgrowth of candida in the intestinal tract. While candida is typically a normally occurring yeast in our bodies, too much of it contributes to the breakdown of our gut lining and the onset of autoimmune responses.
Oregano oil, garlic, or grapefruit seed extract should all be used slowly so that your body acclimates to the change, as a large dose could wipe out the candida altogether and leave your system unbalanced.
Quercetin It's probably not a supplement you've heard of on a regular basis, but quercetin is a highly beneficial compound for healing a leaky gut. On a rudimentary level, this powerful flavonoid seals the gut lining and acts as a preventative barrier.
Deglycyrrhizinated licorice root This supplement packs a double punch, as it not only helps to keep our stomach's mucus alive and well, but it also works to aid in balancing hormones and alleviating adrenal fatigue.
DGL licorice root can be a powerful tool in healing one's gut lining while simultaneously helping to balance the signals being sent to the pituitary gland , which can often malfunction due to a poor diet. N-acetylglucosamine Protection and healing are both found in this supplement, which has become popular in recent years.
Helping to boost the health of the stomach and intestinal lining, it's also a strong anti-inflammatory, helping individuals with IBS, Crohn's disease, and more. These 10 supplements will work quite well to repair a leaky gut and help your digestive system to function on a more regular level, but they also include extra assistance when it comes to healing the rest of your body.
Often times the contributing factors to causing a leaky gut also wreak havoc on our hormones, leaving us feeling out of balance with a variety of symptoms. Additionally, many individuals find that their leaky gut creates so many autoimmune issues, from IBS to arthritis, that regularly exercising becomes a chore that they just can't undertake.
By utilizing the recommended supplements and healing your intestinal permeability, you might even find that increasing your fitness level is a much easier task. Healing a leaky gut takes time and usually cannot be done through supplements alone. Try boosting the effectiveness of these supplements by cutting out potential inflammatory foods from your diet and see if any of your nagging symptoms disappear.
For example, quercetin with bromelain an anti-inflammatory enzyme found in pineapples may be taken to help manage allergies. What are side effects of quercetin? According to a report, most studies have found little to no side effects in people eating nutrient-dense diets high in quercetin or taking supplements by mouth short term.
Is quercetin safe to take daily? Amounts up to milligrams taken twice daily for 12 weeks appear to be safe. However, of course, in very high doses there are some risks.
Side effects can include headaches and tingling of the arms and legs. Very high doses taken intravenously have also been linked to cases of kidney damage, although this seems very rare.
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Let's Be Friends. glycinifermentans, B. eggerthii, O. All the five species identified in this study have been demonstrated to be present in human fecal content, suggesting that these species in the gut are capable of biotransforming quercetin.
Our demonstration of the ability of F. plautii and Lactobacillus species positive control to degrade quercetin is also consistent with the previously published reports [ 23 ] [ 26 ] [ 32 ] [ 33 ]. Although F. plautii was previously reported to degrade quercetin to generate DOPAC, the research described in this report for the first time identified the ability of B.
glycinifermentans to biotransform quercetin to generate 2,4,6-THBA and 3,4-DHBA. glycinifermentans , which was reported to be part of human fecal content by Ghimire et al.
glycinifermentans [ 35 ]. Interestingly, based on the analysis of its complete genome, this bacterium was suggested for use as a probiotic for livestock to enhance immune stimulation, enzyme production and pathogen inhibition [ 36 ].
The link between our observation that it is capable of biotransforming quercetin to generate 2,4,6-THBA and 3,4-DHBA and its suggested use as a probiotic in the previous report [ 36 ] makes this bacterial strain an interesting candidate for the maintenance of human gut health.
The detection of DOPAC as a metabolite of quercetin generated by F. plautii in this study confirms the previous reports in literature [ 32 ]. In this study, we did not detect the presence of 2,4,6-THBA and 3,4-DHBA in the spent medium from F.
Although the reason for this is currently unclear, it is possible that the amounts of the other metabolites 2,4,6-THBA and 3,4-DHBA generated from this bacterium might have been below the detection levels of the HPLC technique employed.
Similarly, the lack of detection of DOPAC in the spent medium from B. glycinifermentans may be attributed to its low levels in the samples. It is to be noted that TBLASTN analysis revealed the presence of homologs of quercetinase, phloretin hydrolase and pirin-like protein in both B.
glycinifermentasns and F. Consistent with this, both species exhibited the presence of transcripts for quercetinase and phloretin hydrolase; however, the abundance of pirin-like protein implicated in quercetin degradation appears to be differentially regulated with a more than two-fold increase in B.
glycinifermentans and a more than two-fold decrease in F. This differential regulation may account for the differences in the metabolites produced as detected by HPLC.
Alternatively, it is also possible that the quercetin degradation pathway utilized by F. plautii is radically different from that of B. glycinifermentans and hence generates different metabolites.
This is supported by the observation that the spent culture supernatant from B. glycinifermentans had quercetin-degrading enzyme activity while the culture supernatant of F.
plautii did not. This observation also suggests that the quercetin-degrading enzymes in B. glycinifermentans and F. plautii are likely to be differentially localized secreted vs.
Furthermore, the degradation kinetics demonstrates that F. plautii completely degrades quercetin within 12 h of incubation, whereas B. glycinifermentans requires around 48 h for complete quercetin degradation. This, along with the minimal enzyme activity detected in the cell lysate, suggests that the degradation of quercetin by F.
plautii may require the presence of live bacterial cells. A recent study by Yang et al. demonstrated the involvement of ene-reductase, chalcone isomerase, enoate reductase and phloretin hydrolase in the generation of metabolites from flavones and flavonols [ 28 ].
Hence, the lack of quercetin degradation in the culture supernatant and minimal activity in the pellet observed in our study may have also been related to the requirement of four different enzymes for the generation of DOPAC from quercetin.
Alternatively, it is also possible that the enzymes involved in F. plautii are sensitive to the experimental conditions or require other cofactors when assayed in vitro, which may not be the case for B. The observation that pirin-like protein, which was previously reported to have quercetin-2,3-dioxygenase activity [ 37 ] , was differentially expressed in B.
plautii may provide a link to the differences observed in the generation of metabolites between the two species of bacteria.
Hence, further research should shed light on the specific pathways utilized by these bacteria for quercetin biotransformation. The importance of 2,4,6-THBA and 3,4-DHBA in the inhibition of cancer cell growth was well-established by our group previously [ 24 ] , and in the present study, we demonstrated that F.
plautii is able to produce DOPAC at concentrations sufficient to produce an antiproliferative effect on cancer cells when tested ex vivo.
It is to be noted that DOPAC has also been shown to inhibit cancer cell proliferation by other investigators in various cancer cell types [ 22 ] [ 26 ] [ 38 ] ; this is believed to occur through its antioxidant properties.
The demonstration of the ability of the bacterial culture supernatant of F. plautii grown in the presence of quercetin to inhibit colony formation is, to our knowledge, the first report showing the direct effect of bacteria-generated metabolites on cancer cell growth and, therefore, is a very significant finding.
We observed that while 1 mL supernatant from the F. plautii culture was sufficient to inhibit colony formation in the HCT cells, 1 mL culture supernatant from the B. glycinifermentans was insufficient to exert a similar inhibitory effect.
Quantification of the metabolites indicated that the amount of 3,4-DHBA generated in our experiments from B. glycinifermentans was lower As an alternative strategy, we performed concentration of the supernatants through rota-evaporation at 65 °C under vacuum conditions.
Addition of the 5× and 10× concentrated samples dissolved in the cell culture medium failed to inhibit cancer cell growth data not shown for the supernatant obtained from the F.
plautii culture. We believe that this could be related to the instability of DOPAC during the process of concentration; for example, temperature may affect the stability of DOPAC.
Therefore, alternative methods of concentration need to be explored to demonstrate the effectiveness of bacterial supernatants where metabolites are generated at lower concentrations such as for B.
glycinifermentans against cancer cell growth. While the human gut is known to harbor — species of bacteria [ 39 ] [ 40 ] , this study investigated the potential of only 94 bacterial species to degrade quercetin.
Therefore, additional screening is required to establish the contribution of other bacterial strains to CRC prevention as well. However, it is interesting to note that of the 94 strains screened, only five exhibited the ability to degrade quercetin.
This suggests that the flavonoid-biotransforming ability may be narrowly restricted to only a few species of bacteria, highlighting the importance of these bacteria in the prevention of CRC. While the focus of our study was on quercetin, it is to be noted that the diet also contains other flavonoid members such as anthocyanins, epigallocatechin gallate, catechins, cyanidinglucoside, etc.
that may be biotransformed by the gut microflora [ 41 ]. For example, DOPAC, 2,4,6-THBA and 3,4-DHBA have been reported to be metabolites produced upon green and black tea consumption [ 22 ] [ 42 ] while 2,4,6-THBA and 3,4-DHBA have been demonstrated to be generated upon the consumption of the anthocyanin, cyanidinglucoside [ 9 ].
Additionally, phenolic acids have also been shown to be produced from the intestinal degradation of fibers by colonic bacteria [ 43 ]. In this study, the bacterial strains were grown individually to screen for their ability to degrade quercetin, but it is still unknown how quercetin may be degraded in the presence of other bacteria, in cocultures.
It is known that some bacterial species influence the growth of others; diet is also suggested to contribute to this selection [ 41 ] [ 44 ]. Therefore, additional studies are required to establish how diet influences the growth of these species and overall degradation of quercetin in vivo.
It will be interesting to explore the metabolism of quercetin by other species of bacteria, enzymes involved in this process and characterize the metabolites generated individually or in a community setting.
Additional studies are also required to test the bacterial culture supernatants containing these metabolites for their ability to inhibit cancer cell proliferation.
Conclusions The research described in this report identified five species of bacteria capable of degrading quercetin to give different bioactive metabolites, some of which have been previously characterized to have antiproliferative effects against cancer cells. This study also established clear differences between two bacterial species B.
plautii in terms of their ability to degrade quercetin; in addition, it also showed the generation of different metabolites. We also demonstrated for the first time the inhibitory effect of the bacterial culture supernatant from F. plautii against cancer cell growth, paving the way for similar studies with other bacterial culture supernatants.
We believe that bacteria-mediated biotransformation of flavonoids and generation of bioactive metabolites are important contributors to colorectal cancer prevention observed in flavonoid-rich diets. References Bischoff, S. Quercetin: Potentials in the prevention and therapy of disease.
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