Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
YAHKUB BABATUNDE MUTALUB
 -- 3497 2022-09-08 12:02:20 |
2 format corrected.
Beatrix Zheng
 + 2 word(s) 3499 2022-09-09 03:51:40 |

Video Upload Options

Do you have a full video?
Send video materials Upload full video

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Mutalub, Y.B.;  Abdulwahab, M.;  Mohammed, A.;  Yahkub, A.M.;  Al-Mhanna, S.B.;  Yusof, W.;  Tang, S.P.;  Rasool, A.H.G.;  Mokhtar, S.S. Gut Microbiota Modulation in Cardiometabolic Diseases Treatment. Encyclopedia. Available online: https://encyclopedia.pub/entry/27003 (accessed on 27 July 2024).
Mutalub YB,  Abdulwahab M,  Mohammed A,  Yahkub AM,  Al-Mhanna SB,  Yusof W, et al. Gut Microbiota Modulation in Cardiometabolic Diseases Treatment. Encyclopedia. Available at: https://encyclopedia.pub/entry/27003. Accessed July 27, 2024.
Mutalub, Yahkub Babatunde, Monsurat Abdulwahab, Alkali Mohammed, Aishat Mutalib Yahkub, Sameer Badri Al-Mhanna, Wardah Yusof, Suk Peng Tang, Aida Hanum Ghulam Rasool, Siti Safiah Mokhtar. "Gut Microbiota Modulation in Cardiometabolic Diseases Treatment" Encyclopedia, https://encyclopedia.pub/entry/27003 (accessed July 27, 2024).
Mutalub, Y.B.,  Abdulwahab, M.,  Mohammed, A.,  Yahkub, A.M.,  Al-Mhanna, S.B.,  Yusof, W.,  Tang, S.P.,  Rasool, A.H.G., & Mokhtar, S.S. (2022, September 08). Gut Microbiota Modulation in Cardiometabolic Diseases Treatment. In Encyclopedia. https://encyclopedia.pub/entry/27003
Mutalub, Yahkub Babatunde, et al. "Gut Microbiota Modulation in Cardiometabolic Diseases Treatment." Encyclopedia. Web. 08 September, 2022.
Gut Microbiota Modulation in Cardiometabolic Diseases Treatment
Edit
This entry is adapted from the peer-reviewed paper 10.3390/foods11172575

The diverse relationship between cardiometabolic diseases (CMD) vulnerability and changes in gut microbiota make-up and metabolites has emphasized that gut microbiota is an unfamiliar modulator of CMD. These connections are possible targets for new CMD therapy. The host–microbiota interaction is made up of various levels at which potential therapeutic interventions can be instituted. These levels include dietary substrates, microbial ecology, and microbiota–host pathways that liberate metabolites that modulate host processes. Agents that inhibit recognized gut microbial enzymes can also be produced. The interesting part of this is that interventions directed at gut microbiota and/or their metabolism in lieu of the host may not necessarily be taken up into the host circulation, hence minimizing the likely adverse effects in comparison to those directed at host metabolism. Among the challenges of therapeutically targeting the gut microbiota are the individual variations, in addition to differences, in gut microbiota make-up, which can affect the action of the medication. This may call for individualized treatment. The gut-microbiota-directed therapeutic concept is based on targeting microbiota compositions, metabolic pathways, and mucosal barrier protection.

dysbiosis cardiovascular disease metabolic disease probiotics prebiotics drug development treatment bacteria metabolite

1. Targeting Whole Gut Microbiota

Gut microbiota, apart from acting as a medication target, may be used as a live treatment in the microbial intervention of management of disorders [1]. Live microbial therapy and/or whole gut microbiota target include fecal microbiota transplantation (FMT), single-strain microorganism or microbial consortia, and the use of antibiotics [1][2][3].
FMT is the process of direct transfer of healthy microbiota from an individual donor into the gut of a dysbiotic recipient with the aim of restoring the normal intestinal microbiota composition and function [4][5][6][7][8]. The recipient individual goes through a gut lavage of laxative therapy before undergoing FMT to improve the success rate of FMT [9]. FMT has been successfully employed for the treatment of Clostridium difficile infection and is lately gaining attention in the management of cardiometabolic diseases (CMD) [4][10][11][12]. A remarkable enhancement of peripheral and liver insulin sensitivity by 176% and 119%, respectively, was observed 6 weeks after fecal transfer from lean healthy individuals to metabolic syndrome patients and the observed enhancement was irrespective of weight differences [10]. This form of transplantation brought about a generalized intestinal microbial abundance, especially a higher proportion of butyrate-generating organisms [13][14]. Furthermore, FMT restored intestinal microbial equilibrium and prevented cardiac cell injury in a mouse myocarditis model [15].
Since the therapeutic application of fecal preparations was a practice of early Chinese [16], intestinal microbiota can be explored as a favorable derivation of live organisms for the treatment of CMD. Currently, the major drawback of FMT is a concomitant transfer of infectious organisms or endotoxins [2][17][18][19][20]. This could be bypassed by transplant of a specific category of bacteria rather than the whole fecal transfer [21][22]. The refinement of the CMD therapeutic role of FMT in terms of composition, route of administration, and dosage calls for additional research.
The application of live organisms to generally adjust microbial ecology in the management of CMD has received some great consideration. Probiotics are live microorganisms that provide their host with health benefits when used in the right quantity [23]. Only very few of them were endorsed as drugs, and the majority are being used as food supplements. They can be utilized therapeutically for varying cardiometabolic conditions. Remarkable reductions in blood lipid and/or glucose levels were observed following patient consumption of Bifidobacteria- and Lactobacilli-containing probiotics [24][25][26]. L. acidophilus ATCC 4358 treatment lessened atherosclerosis in ApoE−/− mice [27]. Supplementation with probiotics also enhanced the metabolic profiles of diabetic patients [28].
Intake of L. plantarum by carotid atherosclerotic individuals increased bacterial diversity and affected intestinal SCFA generation [29]. Additionally, intake of L. acidophilus, L. casei, and L. rhamnosus each induced differential gene regulatory pathways in the human mucosa, as determined by transcriptome analysis. These response profiles were similar to those obtained for specific bioactive molecules and drugs, indicating the potential of gut microbiota used as naturally evolved drug candidates [30]. Obesity and type 2 diabetes (T2DM) were associated with reduced availability of intestinal A. muciniphila [31][32]. Improved metabolic profiles were therefore observed in obese and diabetic mice given A. muciniphila [33]. Christensenella minuta treatment was demonstrated to change the gut microbiota community and prevent obesity in mice [34]. Lactobacillus rhamnosus treatment decreased infarct dimensions and enhanced heart functions [35]. Saccharonyces boulardii was documented to enhance left ventricular ejection fraction in HF patients [36]. Other examples of probiotics are Enterococcus, Bifidobacterium, and Streptococcus [37]. Therapeutically administered probiotics to immunodeficient, debilitated patients may turn to opportunistic pathogens that can cause endocarditis [38]. This means that the probiotics approach in susceptible individuals should be used with caution.
Other research revealed contradictory effects in the use of probiotics on CVD and risk factors [17][39] probably due to preintervention microbial variability. For therapeutic purposes, an isolated microorganism or a specific category of microorganisms, known as consortia, can be established while trials in humans are conducted to establish their safety and efficacy.
Dietary habits also determine intestinal microbial heterogeneity. Acute dietary modification has resulted in commensurate alterations in the composition and quantity of gut microbiota [40]. Even though individual gut microbiota tend to be resilient, the abrupt nutritional alteration can adjust the microbial ecology [41][42][43][44]. Alterations in dietary sugar content were associated with alterations in E. rectale and Roseburia [45][46].
Some of the currently available antihypertensive drugs have been demonstrated to exert their action via gut microbiota modulation. For example, captopril, in addition to its inhibiting effect on the angiotensin-converting enzyme, also proliferates the gut bacteria Allobaculum. As a result of this bacteria, the stoppage of captopril treatment preserves the antihypertensive state [47]. Similarly, angiotensin II receptor blockers were demonstrated to maintain Lactobacillus levels, prevent gut dysbiosis, and restore the normal F/B ratio [48][49][50]. Moreover, statin drugs have been demonstrated to modulate gut microbiota. For instance, atorvastatin elevated proteobacteria levels and decreased Firmicutes levels in addition to normalization of dominant taxa in high-fat-diet-fed rats [51][52].
Pathogens are implicated in the pathophysiology of some CVDs, such as atherosclerosis [53][54][55][56]. Therefore, researchers have given attention to the use of antibiotics for the eradication of pathogen-associated CVD. For instance, decreased lipoprotein levels result from ampicillin therapy [57], while a reduction in systolic blood pressure was observed in spontaneously hypertensive rats following minocycline and vancomycin treatment [58]. Depletion of microorganisms and subsequently decreased plasma leptin and myocardial infarction ensued from oral vancomycin administration to rats [59][60]. Oral minocycline therapy modified hypertension after restoring gut microbiota balance and decreasing the F/B ratio [61][62]. This therapeutic approach is, however, limited by the restriction of effect to the period of antibiotic administration, therefore requiring chronic use, with its consequent likelihood of antibiotic resistance and depletion of beneficial bacteria [2][3][63]. There is presently no proof of the overall beneficial effect of vague antibiotic therapy in human CVD management. Antibiotics, therefore, appear to be more appropriate for the elimination of disease-causing microorganisms, instead of a prolonged prophylactic application.
Higher Bacteroidetes and lower Firmicutes were observed after 10 weeks of moderate to severe aerobic exercise by obese adults [64]. Similarly, regular exercise attenuates obesity development and causes changes in the gut microbiota composition in a mice obesity model [65][66]. Furthermore, exercise increased the percentage of Bacteroidetes and decreased the percentage of Firmicutes regardless of diet [67], and high-intensity interval training increased the gut Bacteroidetes to Firmicutes ratio during diet-induced obesity [68]. Rugby players were found to have a higher number and more diverse gut microbiota compared to their non-athletic counterparts of similar age and body mass index [69]. This research also revealed that exercise may increase the α-diversity of gut microbiota and the abundance of the bacterial genus Akkermansia. Voluntary exercise impacted the Bacteroidetes/Firmicutes balance and prevented diet-induced obesity, in addition to causing improved glucose tolerance [70].
A recent study has demonstrated a depletion of opportunistic pathogens and accumulation of intestinal-wall-protecting bacteria in association with improved lipid profile and insulin sensitivity after nutritional intervention with prebiotics and whole grains [71]. Anthocyanin-containing fruits such as blueberries could also heighten the diversity of gut microbiota [72]. Dietary fortification with magnesium acetate also modified hypertension after the restoration of intestinal microbiota balance and decreased the F/B ratio [61][62].

2. Treatment Targeting LPS/Strengthen Intestinal Barrier

Interventions leading to the reduction of circulating LPS have been explored for the management of CMD. Some of the interventions are listed below:
The high quantities of circulating LPS associated with certain CMD could be reduced through physical exercise [73][74]. This will subsequently ameliorate CMD. For instance, physical exercise led to changes in the structure of intestinal bacteria that favor reduced LPS and avert heart impairment in mice with myocardial infarction [75]. In rats fed a high-fat diet, both acute and chronic exercise may induce a significant decrease in the TLR4-mediated signaling pathway in the liver, muscle, and adipose tissue, accompanied by the concomittant reduction in serum LPS levels and improved insulin signaling and sensitivity in metabolic target tissues [76][77].
Decrease atherosclerosis of the aorta related to reduced plasma and fecal LPS as well as lower gut penetrability was observed following oral administration of Akkermansia muciniphila to Apolipoprotein E (ApoE)−/− mice fed with a Western diet [78]. Similarly, reduced circulating LPS from A muciniphila treatment of metabolic syndrome patients improved their lipid profile and insulin resistance without alteration of body weight [79].
Antibiotics can reduce the fecal and circulating LPS. Rifaximin, tobramycin, and polymyxin B, for instance, could decrease gut bacterial translocation and decrease gut LPS, aside from their regular bacteriostatic and bactericidal action [80][81]. The limitations of antibiotic intervention were nonetheless mentioned earlier on.

3. Treatment Targeting Inflammation

Studies have associated inflammation with CMD [82]. The recognition of intestinal microbiota associated with immunological reactions involved in the pathogenesis of CMD can serve as a therapeutic target in inflammation-associated CMD [3]. Prebiotics are indigestible food materials that enhance the growth of beneficial gut microorganisms [83]. Inflammatory cell invasion in rats was significantly decreased with prebiotic oligofructose [84]. An appreciable alleviation of inflammation and hypertension was demonstrated in patients with hypertension following consumption of the dietary approach to stop hypertension (DASH) and the Mediterranean diet [85][86][87][88]. The application of immunotherapy may however be limited by a higher likelihood of opportunistic infections, especially in individuals with multimorbidity [83].

4. Treatment Targeting SCFAs

Several researchers including Gordon [82] have evaluated the role of SCFAs in CMD. The enhanced insulin sensitivity observed in metabolic syndrome patients after FMT from lean individuals was linked to higher butyrate-generating microorganisms and subsequent higher fecal SCFAs [10].
Supplementation with 1% butyrate halved aortic lesions in mice [89][90]. SCFAs also reduce hypertension in animals [91]. Another research revealed that treatment with Roseburia intestinalis (butyrate-liberating bacteria) attenuated atherosclerosis development via butyrate [92]. Lifestyle modification (including diet and exercise), which is presently a vital clinical intervention in the management of CMD, alters gut microbiota composition and function, including SCFA production [93].
Studies have demonstrated the attenuation of CMD by SCFAs liberated from gut microbiota degradation of prebiotic fibers [94][95][96]. Prebiotics are indigestible molecules that provide a beneficial effect to the host via alteration in the make-up and/or actions of the gut microbiota. They are usually in form of complex saccharides or oligosaccharides [97]. An energetic tool in the prevention and treatment of CMD is the regulation of gut microbiota through diet. For example, intestinal microbiota modulation via a high-fiber diet and acetate intake attenuated cardiac diseases and hypertension [62]. Similarly, modulation of intestinal microbiota with a high-fiber diet resulted in the growth of beneficial bacteria, heightened generation of SCFAs, and caused attenuation of elevated blood pressure [98]. A high abundance of acetate-liberating intestinal bacteria and subsequent remarkable reduction in fibrosis and hypertrophy of heart cells, as well as blood pressure and HF prevention, were demonstrated in mice fed a high-fiber diet [62]. Furthermore, hypertension reversal ensued through intake of butyrate- and acetate-generating corn and Clostridium butyricum by hypertensive rodents [99]. Additionally, oral intake of butyrate, propionate and acetate decreased insulin resistance and body weight in high-fat-diet-induced obese mice [100].
A high generation of SCFA can also result from the consumption of vegetables, legumes, and fruits [101]. The favorable role of a plant-based diet compared to animal-based ones has been attributed to their ability to modulate local and systemic SCFA generation [93]. A remarkable decrease in fecal butyrate and acetate level was demonstrated with the shifting of individuals from plant- to animal-based foods [44]. Propionate averts hypertension, vascular dysfunction, heart fibrosis, and hypertrophy [102]. A decrease in adverse cardiac remodeling and hypertension ensued when gut microbial metabolite (acetate) or a prebiotic (high-fiber diet) was administered in a rodent hypertension model [62]. Furthermore, carotid artery endothelial dysfunction was attenuated following administration of prebiotic inulin-like fructans to ApoE−/− mice [103]. Prebiotic inulin treatment also remarkably reduced atherosclerotic lesions in ApoE−/− mice [104]. A plant polysaccharide-rich diet increased butyrate generation by gut microbiota and attenuated atherosclerosis compared to low-plant polysaccharide diets [92]. Similarly, atherosclerosis was attenuated by microbiota of ApoE−/− mice when fed a high-plant-polysaccharide-containing diet, as contrasted to a Western diet-fed one [105]. Augmentation of the diet with ginger also modifies gut microbial ecology and incites enhanced metabolism of fatty acids [106].
Studies have revealed the ability of probiotics to positively modulate fat metabolism [107][108]. The probable mechanisms of probiotics involve opposition of disease-causing organisms, the liberation of antimicrobial agents, and pH modification [109][110]. Lactobacillus sp. administration was linked with remarkable alteration in colonic SCFAs in carotid atherosclerotic patients [29]. Symbiotic formulations are dietary adjuncts with a blend of probiotics and prebiotics that can modify intestinal metabolism [99]. The commonly adjoined probiotics in symbiotic formulations are Bifidobacteria, Lactobacilli, S. boulardii, and B. coagulans, while the prebiotics are oligosaccharides, dietary fibers, and inulin [111].
FMT to metabolic syndrome patients from lean individuals was linked to a higher abundance of butyrate-generating bacteria (such as Roseburia) and resulted in improved insulin sensitivity [10].
Current studies demonstrate that exercise modifies the intestinal microbiota for its cardiovascular effects. Research revealed that it increases the ratio of Firmicutes to Bacteroidetes [112][113] as well as elevates the amount of the microbial product butyrate [114]. The positive effect of exercise on intestinal microbiota was interim and abated following the stoppage of the exercise [114]. This makes a longer period of exercise a necessity for remarkable long-lasting effects [2]. The gut metabolism of athletes is found to generate a high level of SCFA [115]. Voluntary running in animals is also associated with microbiota diversity and attendant elevated butyrate levels [116]. The butyrate may inhibit the activity of histone deacetylases and therefore influence immune modulation and decrease oxidative stress [117]. It can also regulate gut motility and barrier integrity as well as inflammation and visceral sensitivity [117][118]. All these partake in CMD modulation. Huang et al. [119] studied rats and demonstrated a pronounced antioxidant function and tricarboxylic acid cycle with endurance training. With regards to the use of exercise to modulate gut microbiota for CMD treatment, further research is needed to answer the questions about the types, timing, and conditions of exercise to achieve a remarkable impact on CMD.
Favorable effects of SCFAs have been demonstrated in hypertension models in rats. Local inoculation of acetate into the colon overturned hypertension in rats [120]. Oral administration of propionate led to enhanced vascular action, decreased blood pressure, and adverse cardiac events in hypertensive mice [102]. Butyrate or propionate administration prevents myocardial harm in hypertension models [91][102]. Sodium butyrate therapy in rodents resulted in improved insulin sensitivity and attenuation of obesity [121]. Tributyrin was synthesized to solve butyrate’s problem of offensive taste and odor. It is a prodrug that carries three molecules of butyrate esterified to glycerol and with comparable cardiometabolic action to and better pharmacokinetic parameters than butyrate [122]. Tributyrin treatment of obese mice diminished insulin resistance and inflammation [1]. Another research revealed that fat accumulation and atherosclerosis were remarkably attenuated with tributyrin treatment in ApoE−/− mice. This is an optimistic approach for CVD prophylaxis [92].

5. Treatment Targeting TMA

Therapeutic approaches that are directed toward halting TMAO generation and elimination of TMAO and its progenitor (TMA) have gained recognition owing to the association of TMAO with cardiometabolic diseases by several studies, as mentioned earlier. Hence, targeting the gut microbiota for reduction of TMA generation will be a likely treatment strategy for CMD [1]. Apart from pharmacological agents, probiotics can be employed for the inhibition of metabolic pathways in gut microbes to reduce TMAO liberation [123].
Mediterranean diet consumption led to remarkably reduced TMAO and could attenuate CMD [124][125]. CMD can be prevented by limiting the intake of a choline/carnitine-rich diet since nutritional intake is the main source of TMAO [126]. Western diets are carnitine/choline-rich while vegetarian diets are carnitine-choline depleted [106][127]. A high-fiber diet decreased plasma TMAO [128]. Although there is no consensus on the effect of saturated fat and red meat intake on TMAO levels [106][129][130], individuals following a vegetarian diet regimen had reduced plasma and urinary TMAO [97][131]. It is therefore thought that this dietary approach could reduce TMAO generation and subsequently attenuate CMD [132].
It is postulated that the transfer of low TMAO-liberating microbiota to patients with heart failure or its risk factors could decrease TMAO, yet none of such has been demonstrated clinically [83].
Broad-spectrum antibiotic administration to individuals led to decreased intestinal microbiota and a remarkable reduction in TMAO levels [133][134]. The use of broad-spectrum antibiotics in elderly mice reduced plasma TMAO and subsequently attenuated endothelial dysfunction and aortic stiffening to a similar level as the young mice [135]. CVD prevention in humans using long-term antibiotics is not practicable due to the previously mentioned challenges of this approach [3].
Reduction in TMAO and altered platelet aggregation were observed in individuals with high TMAO that were treated with low-dose aspirin [127][136]. The low-dose aspirin can also change the gut microbial composition [137].
Targeting bacterial enzymes involved in TMA generation for inhibition are being investigated as a preventive or therapeutic approach for CMD [126][138][139][140]. For example, a structural analog of choline 3,3-dimethyl-1-butanol (DMB) is a model microbial TMA lyase inhibitor used for this purpose [141]. Reduction in TMA/TMAO ensued inhibition of TMA lyase and inhibition of TMA lyase modified CVD [142]. Foam cell production and subsequent atherosclerosis were impaired after oral administration of DMB, which resulted in decreased plasma TMAO in ApoE−/−mice on a choline-augmented diet [138]. Another study also demonstrated the anti-atherogenesis effect of DMB [143]. Furthermore, decreased ventricular remodeling and enhanced hemodynamic status followed DMB administration [144]. More potent TMA lyase inhibitors such as fluoromethylcholine, iodomethylcholine, chloromethylcholine, and bromomethylcholine have been invented. These compounds specifically act locally on the gut microbiota with minimal systemic exposure of the host, thereby limiting adverse effects [3][145]. TMA lyase inhibitors, including DMB, are harmless to the microbes. Therefore, they do not cause selective pressure like antibiotics do, and the risk of resistance is minimal [3].
Aside from TMA lyase (CutC/D), other enzymes involved in the generation of TMA from other precursors include CntA/B [140], betaine reductase [146], TMAO reductase [147], and YeaW/X [148]. Clinical trials have demonstrated that dietary indoles of Brussels sprouts inhibited FMO3 and thereby prevented the conversion of TMA to TMAO [149]. Drug development that targets a reduction of TMAO production via inhibition of TMA lyase is preferred to specific FMO3 inhibition because elevated plasma levels of TMA result in a condition termed trimethylaminuria, which brings about an offensive “fishy” odor [150]. Another enzyme inhibitor (meldonium), which is an analog of carnitine, produces an anti-atherosclerotic effect by competitively inhibiting microbial carnitine palmitoyltransferase-1 (CPT1), resulting in the attenuation of microbial TMA generation [151]. Furthermore, phospholipase D (PLD) is one more intestinal microbial enzyme that can be targeted for drug development. PLD is involved in TMA generation by liberating free choline from phosphatidylcholine, the predominant dietary form of choline. The good news is that gut microbial PLD can be preferentially inhibited without affecting the host enzyme, owing to the phylogenetic differences between host and microbial PLD enzymes [152]. Therefore, future therapeutic action with innocuous enzyme inhibitors directed at gut microbiota presents an innovative strategy for the prevention and treatment of CMD. This nonetheless requires clinical studies for validation [3][17].

6. Treatment Targeting Bile Acids

A secondary bile acid, ursodeoxycholic acid (UDCA), was studied as an innovative treatment for rodent obesity [153]. An FXR agonist and semisynthetic analog of bile acid, obeticholic was thought to have the ability to decrease bacterial translocation and inflammation [154]. It was the first FXR agonist to reach the clinical stage [155]. Investigations have demonstrated that obeticholic modified fat metabolism and improve insulin sensitivity as a result of the role FXR signaling plays in the control of lipid and glucose balance [1]. Similarly, TGR5 agonists enhance a myocardial reaction to stress in mice [156], hence they, as well as FXR agonists, can be innovative targets for the management of heart failure [83]. Furthermore, targeting BSH microbiota–host interplay could be a strategy for metabolic disorders and obesity since studies have shown that microbial BSH action may remarkably decrease weight gain as well as plasma cholesterol [157][158]. Statin drugs were demonstrated to affect the BA pool as well as decrease gut butyrate generation [159].

7. Targeting Other Metabolites/Enzymes

Significant advancement has been recorded in the comprehension of intestinal microbial metabolism. The exposition of more microbial products allows additional likely therapeutic targets for CMD [1]. The intestinal microbiota tryptophan decarboxylase was identified to be accountable for the generation of tryptamine [160]. Microbial dissimilatory sulfite reductases (DsrAB) are responsible for hydrogen sulfide production [161] while tryptophanases lead to indole generation [162]. The gut microbiota glycyl radical enzyme was also recognized to break the C-S bond of taurine to produce hydrogen sulfide [163]. The applicability of the mentioned microbial enzymes and the production of their inhibitors as innovative therapeutic targets require further studies. This is with the aim of improving the liberation of useful metabolites and attenuating the generation of harmful ones [1].

References

  1. Du, Y.; Li, X.; Su, C.; Wang, L.; Jiang, J.; Hong, B. The human gut microbiome—A new and exciting avenue in cardiovascular drug discovery. Expert Opin. Drug Discov. 2019, 14, 1037–1052.
  2. Xu, H.; Wang, X.; Feng, W.; Liu, Q.; Zhou, S.; Liu, Q.; Cai, L. The gut microbiota and its interactions with cardiovascular disease. Microb. Biotechnol. 2020, 13, 637–656.
  3. Witkowski, M.; Weeks, T.L.; Hazen, S.L. Gut Microbiota and Cardiovascular Disease. Circ. Res. 2020, 127, 553–570.
  4. Barnes, D.; Park, K.T. Donor Considerations in Fecal Microbiota Transplantation. Curr. Gastroenterol. Rep. 2017, 19, 10.
  5. Fuentes, S.; de Vos, W.M. How to Manipulate the Microbiota: Fecal Microbiota Transplantation. Adv. Exp. Med. Biol. 2016, 902, 143–153.
  6. Shreiner, A.B.; Kao, J.Y.; Young, V.B. The gut microbiome in health and in disease. Curr. Opin. Gastroenterol. 2015, 31, 69–75.
  7. Ursell, L.K.; Metcalf, J.L.; Parfrey, L.W.; Knight, R. Defining the human microbiome. Nutr. Rev. 2012, 70 (Suppl. 1), S38–S44.
  8. Gallo, A.; Passaro, G.; Gasbarrini, A.; Landolfi, R.; Montalto, M. Modulation of microbiota as treatment for intestinal inflammatory disorders: An uptodate. World J. Gastroenterol. 2016, 22, 7186–7202.
  9. Cooper, S.; Mathews, R.; Bushar, L.; Paddock, B.; Wood, J.; Tammara, R. The Human Microbiome: Composition and Change Reflecting Health and Disease. HAPS Educ. 2019, 23, 432–445.
  10. Vrieze, A.; Van Nood, E.; Holleman, F.; Salojärvi, J.; Kootte, R.S.; Bartelsman, J.F.; Dallinga-Thie, G.M.; Ackermans, M.T.; Serlie, M.J.; Oozeer, R.; et al. Transfer of Intestinal Microbiota From Lean Donors Increases Insulin Sensitivity in Individuals With Metabolic Syndrome. Gastroenterology 2012, 143, 913–916.e7.
  11. Gregory, J.C.; Buffa, J.A.; Org, E.; Wang, Z.; Levison, B.S.; Zhu, W.; Wagner, M.A.; Bennett, B.J.; Li, L.; DiDonato, J.A.; et al. Transmission of Atherosclerosis Susceptibility with Gut Microbial Transplantation. J. Biol. Chem. 2015, 290, 5647–5660.
  12. Proctor, L.M. The Human Microbiome Project in 2011 and Beyond. Cell Host Microbe 2011, 10, 287–291.
  13. Qin, J.; Li, Y.; Cai, Z.; Li, S.; Zhu, J.; Zhang, F.; Liang, S.; Zhang, W.; Guan, Y.; Shen, D.; et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 2012, 490, 55–60.
  14. Karlsson, F.H.; Tremaroli, V.; Nookaew, I.; Bergström, G.; Behre, C.J.; Fagerberg, B.; Nielsen, J.; Bäckhed, F. Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature 2013, 498, 99–103.
  15. Hu, X.-F.; Zhang, W.-Y.; Wen, Q.; Chen, W.-J.; Wang, Z.-M.; Chen, J.; Zhu, F.; Liu, K.; Cheng, L.-X.; Yang, J.; et al. Fecal microbiota transplantation alleviates myocardial damage in myocarditis by restoring the microbiota composition. Pharmacol. Res. 2019, 139, 412–421.
  16. Drew, L. Microbiota: Reseeding the gut. Nature 2016, 540, S109–S112.
  17. Tang, W.W.; Kitai, T.; Hazen, S.L. Gut Microbiota in Cardiovascular Health and Disease. Circ. Res. 2017, 120, 1183–1196.
  18. Brandt, L.J. FMT: First step in a long journey. Am. J. Gastroenterol. 2013, 108, 1367–1368.
  19. De Leon, L.M.; Watson, J.B.; Kelly, C.R. Transient Flare of Ulcerative Colitis After Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection. Clin. Gastroenterol. Hepatol. 2013, 11, 1036–1038.
  20. Chehoud, C.; Dryga, A.; Hwang, Y.; Nagy-Szakal, D.; Hollister, E.B.; Luna, R.A.; Versalovic, J.; Kellermayer, R.; Bushman, F.D. Transfer of Viral Communities between Human Individuals during Fecal Microbiota Transplantation. mBio 2016, 7, e00322-16.
  21. Brand, M.W.; Wannemuehler, M.J.; Phillips, G.J.; Proctor, A.; Overstreet, A.-M.; Jergens, A.E.; Orcutt, R.P.; Fox, J.G. The Altered Schaedler Flora: Continued Applications of a Defined Murine Microbial Community. ILAR J. 2015, 56, 169–178.
  22. Tamburini, S.; Shen, N.; Wu, H.C.; Clemente, S.T.N.S.J.C. The microbiome in early life: Implications for health outcomes. Nat. Med. 2016, 22, 713–722.
  23. Hill, C.; Guarner, F.; Reid, G.; Gibson, G.R.; Merenstein, D.J.; Pot, B.; Morelli, L.; Canani, R.B.; Flint, H.J.; Salminen, S.; et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat. Rev. Gastroenterol. Hepatol. 2014, 11, 506–514.
  24. Yadav, H.; Jain, S.; Sinha, P. Antidiabetic effect of probiotic dahi containing Lactobacillus acidophilus and Lactobacillus casei in high fructose fed rats. Nutrition 2007, 23, 62–68.
  25. Tahri, K.; Grille, J.P.; Schneider, F. Bifidobacteria Strain Behavior Toward Cholesterol: Coprecipitation with Bile Salts and Assimilation. Curr. Microbiol. 1996, 33, 187–193.
  26. Nguyen, T.; Kang, J.; Lee, M. Characterization of Lactobacillus plantarum PH04, a potential probiotic bacterium with cholesterol-lowering effects. Int. J. Food Microbiol. 2007, 113, 358–361.
  27. Huang, Y.; Wang, J.; Quan, G.; Wang, X.; Yang, L.; Zhong, L. Lactobacillus acidophilus ATCC 4356 Prevents Atherosclerosis via Inhibition of Intestinal Cholesterol Absorption in Apolipoprotein E-Knockout Mice. Appl. Environ. Microbiol. 2014, 80, 7496–7504.
  28. Asemi, Z.; Zare, Z.; Shakeri, H.; Sabihi, S.-S.; Esmaillzadeh, A. Effect of Multispecies Probiotic Supplements on Metabolic Profiles, hs-CRP, and Oxidative Stress in Patients with Type 2 Diabetes. Ann. Nutr. Metab. 2013, 63, 1–9.
  29. Karlsson, C.; Ahrné, S.; Molin, G.; Berggren, A.; Palmquist, I.; Fredrikson, G.N.; Jeppsson, B. Probiotic therapy to men with incipient arteriosclerosis initiates increased bacterial diversity in colon: A randomized controlled trial. Atherosclerosis 2010, 208, 228–233.
  30. van Baarlen, P.; Troost, F.; van der Meer, C.; Hooiveld, G.; Boekschoten, M.; Brummer, R.J.M.; Kleerebezem, M. Human mucosal in vivo transcriptome responses to three lactobacilli indicate how probiotics may modulate human cellular pathways. Proc. Natl. Acad. Sci. USA 2010, 108, 4562–4569.
  31. Shin, N.R.; Lee, J.C.; Lee, H.Y.; Kim, M.S.; Whon, T.W.; Lee, M.S.; Bae, J.W. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut 2014, 63, 727–735.
  32. Forslund, K.; Hildebrand, F.; Nielsen, T.; Falony, G.; Le Chatelier, E.; Sunagawa, S.; Prifti, E.; Vieira-Silva, S.; Gudmundsdottir, V.; Krogh Pedersen, H.; et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature 2015, 528, 262–266.
  33. Plovier, H.; Everard, A.; Druart, C.; Depommier, C.; Van Hul, M.; Geurts, L.; Chilloux, J.; Ottman, N.; Duparc, T.; Lichtenstein, L.; et al. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat. Med. 2016, 23, 107–113.
  34. Goodrich, J.K.; Waters, J.L.; Poole, A.C.; Sutter, J.L.; Koren, O.; Blekhman, R.; Beaumont, M.; Van Treuren, W.; Knight, R.; Bell, J.T.; et al. Human Genetics Shape the Gut Microbiome. Cell 2014, 159, 789–799.
  35. Gan, X.T.; Ettinger, G.; Huang, C.X.; Burton, J.P.; Haist, J.V.; Rajapurohitam, V.; Sidaway, J.E.; Martin, G.; Gloor, G.B.; Swann, J.R.; et al. Probiotic Administration Attenuates Myocardial Hypertrophy and Heart Failure After Myocardial Infarction in the Rat. Circ. Heart Fail. 2014, 7, 491–499.
  36. Costanza, A.C.; Moscavitch, S.D.; Neto, H.C.F.; Mesquita, E.T. Probiotic therapy with Saccharomyces boulardii for heart failure patients: A randomized, double-blind, placebo-controlled pilot trial. Int. J. Cardiol. 2015, 179, 348–350.
  37. Markowiak, P.; Śliżewska, K. Effects of Probiotics, Prebiotics, and Synbiotics on Human Health. Nutrients 2017, 9, 1021.
  38. Kothari, D.; Patel, S.; Kim, S.-K. Probiotic supplements might not be universally-effective and safe: A review. Biomed. Pharmacother. 2019, 111, 537–547.
  39. Jonsson, A.L.; Bäckhed, F. Role of gut microbiota in atherosclerosis. Nat. Rev. Cardiol. 2017, 14, 79–87.
  40. Khalesi, S.; Sun, J.; Buys, N.; Jayasinghe, R. Effect of probiotics on blood pressure: A systematic review and meta-analysis of randomized, controlled trials. Hypertension 2014, 64, 897–903.
  41. Xu, Z.; Knight, R. Dietary effects on human gut microbiome diversity. Br. J. Nutr. 2015, 113, S1–S5.
  42. Voreades, N.; Kozil, A.; Weir, T.L. Diet and the development of the human intestinal microbiome. Front. Microbiol. 2014, 5, 494.
  43. Ravussin, Y.; Koren, O.; Spor, A.; LeDuc, C.; Gutman, R.; Stombaugh, J.; Knight, R.; Ley, R.E.; Leibel, R.L. Responses of Gut Microbiota to Diet Composition and Weight Loss in Lean and Obese Mice. Obesity 2012, 20, 738–747.
  44. David, L.A.; Maurice, C.F.; Carmody, R.N.; Gootenberg, D.B.; Button, J.E.; Wolfe, B.E.; Ling, A.V.; Devlin, A.S.; Varma, Y.; Fischbach, M.A.; et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 2014, 505, 559–563.
  45. Duncan, S.H.; Lobley, G.E.; Holtrop, G.; Ince, J.; Johnstone, A.M.; Louis, P.; Flint, H.J. Human Colonic Microbiota Associated with Diet, Obesity and Weight Loss. Int. J. Obes. 2008, 32, 1720–1724.
  46. Duncan, S.H.; Belenguer, A.; Holtrop, G.; Johnstone, A.M.; Flint, H.J.; Lobley, G.E. Reduced Dietary Intake of Carbohydrates by Obese Subjects Results in Decreased Concentrations of Butyrate and Butyrate-Producing Bacteria in Feces. Appl. Environ. Microbiol. 2007, 73, 1073–1078.
  47. Yang, T.; Aquino, V.; Lobaton, G.O.; Li, H.B.; Colon-Perez, L.; Goel, R.; Qi, Y.F.; Zubcevic, J.; Febo, M.; Richards, E.M.; et al. Sustained Captopril-Induced Reduction in Blood Pressure Is Associated With Alterations in Gut-Brain Axis in the Spontaneously Hypertensive Rat. J. Am. Heart Assoc. 2019, 8, e010721.
  48. Yisireyili, M.; Uchida, Y.; Yamamoto, K.; Nakayama, T.; Cheng, X.W.; Matsushita, T.; Nakamura, S.; Murohara, T.; Takeshita, K. Angiotensin receptor blocker irbesartan reduces stress-induced intestinal inflammation via AT1a signaling and ACE2-dependent mechanism in mice. Brain, Behav. Immun. 2018, 69, 167–179.
  49. Wu, D.; Tang, X.; Ding, L.; Cui, J.; Wang, P.; Du, X.; Yin, J.; Wang, W.; Chen, Y.; Zhang, T. Candesartan attenuates hypertension-associated pathophysiological alterations in the gut. Biomed. Pharmacother. 2019, 116, 109040.
  50. Wu, R.; Mei, X.; Wang, J.; Sun, W.; Xue, T.; Lin, C.; Xu, D. Zn(ii)-Curcumin supplementation alleviates gut dysbiosis and zinc dyshomeostasis during doxorubicin-induced cardiotoxicity in rats. Food Funct. 2019, 10, 5587–5604.
  51. Khan, M.Y.; Dirweesh, A.; Khurshid, T.; Siddiqui, W.J. Comparing fecal microbiota transplantation to standard-of-care treatment for recurrent Clostridium difficile infection: A systematic review and meta-analysis. Eur. J. Gastroenterol. Hepatol. 2018, 30, 1309–1317.
  52. Khan, T.J.; Ahmed, Y.M.; Zamzami, M.A.; Mohamed, S.A.; Khan, I.; Baothman, O.A.S.; Mehanna, M.G.; Yasir, M. Effect of atorvastatin on the gut microbiota of high fat diet-induced hypercholesterolemic rats. Sci. Rep. 2018, 8, 662.
  53. Epstein, S.; Speir, E.; Zhou, Y.; Guetta, E.; Leon, M.; Finkel, T. The role of infection in restenosis and atherosclerosis: Focus on cytomegalovirus. Lancet 1996, 348, S13–S17.
  54. Patel, P.; Mendall, M.A.; Carrington, D.; Strachan, D.P.; Leatham, E.; Molineaux, N.; Levy, J.; Blakeston, C.; Seymour, C.A.; Camm, A.J.; et al. Association of Helicobacter pylori and Chlamydia pneumoniae infections with coronary heart disease and cardiovascular risk factors. BMJ 1995, 311, 711–714.
  55. Danesh, J.; Collins, R.; Peto, R. Chronic infections and coronary heart disease: Is there a link? Lancet 1997, 350, 430–436.
  56. Saikku, P.; Mattila, K.; Nieminen, M.S.; Huttunen, J.K.; Leinonen, M.; Ekman, M.R.; Mäkelä, P.H.; Valtonen, V. Serological Evidence of an Association of a Novel Chlamydia, Twar, with Chronic Coronary Heart Disease and Acute Myocardial Infarction. Lancet 1988, 332, 983–986.
  57. Rune, I.; Rolin, B.; Larsen, C.; Nielsen, D.S.; Kanter, J.; Bornfeldt, K.E.; Lykkesfeldt, J.; Buschard, K.; Kirk, R.K.; Christoffersen, B.; et al. Modulating the Gut Microbiota Improves Glucose Tolerance, Lipoprotein Profile and Atherosclerotic Plaque Development in ApoE-Deficient Mice. PLoS ONE 2016, 11, e0146439.
  58. Galla, S.; Chakraborty, S.; Cheng, X.; Yeo, J.; Mell, B.; Zhang, H.; Mathew, A.V.; Vijay-Kumar, M.; Joe, B. Disparate effects of antibiotics on hypertension. Physiol. Genom. 2018, 50, 837–845.
  59. Lam, V.; Su, J.; Hsu, A.; Gross, G.J.; Salzman, N.H.; Baker, J.E. Intestinal Microbial Metabolites Are Linked to Severity of Myocardial Infarction in Rats. PLoS ONE 2016, 11, e0160840.
  60. Lam, V.; Su, J.; Koprowski, S.; Hsu, A.; Tweddell, J.S.; Rafiee, P.; Gross, G.J.; Salzman, N.H.; Baker, J.E. Intestinal microbiota determine severity of myocardial infarction in rats. FASEB J. 2012, 26, 1727–1735.
  61. Yang, T.; Santisteban, M.M.; Rodriguez, V.; Li, E.; Ahmari, N.; Carvajal, J.M.; Zadeh, M.; Gong, M.; Qi, Y.; Zubcevic, J.; et al. Gut Dysbiosis Is Linked to Hypertension. Hypertension 2015, 65, 1331–1340.
  62. Marques, F.Z.; Nelson, E.; Chu, P.-Y.; Horlock, D.; Fiedler, A.; Ziemann, M.; Tan, J.K.; Kuruppu, S.; Rajapakse, N.W.; El-Osta, A.; et al. High-Fiber Diet and Acetate Supplementation Change the Gut Microbiota and Prevent the Development of Hypertension and Heart Failure in Hypertensive Mice. Circulation 2017, 135, 964–977.
  63. Chen, X.; Li, H.-Y.; Hu, X.-M.; Zhang, Y.; Zhang, S.-Y. Current understanding of gut microbiota alterations and related therapeutic intervention strategies in heart failure. Chin. Med J. 2019, 132, 1843–1855.
  64. Santacruz, A.; Marcos, A.; Wärnberg, J.; Martí, A.; Martin-Matillas, M.; Campoy, C.; Moreno, L.A.; Veiga, O.; Redondo-Figuero, C.; Garagorri, J.M.; et al. Interplay Between Weight Loss and Gut Microbiota Composition in Overweight Adolescents. Obesity 2009, 17, 1906–1915.
  65. Mailing, L.J.; Allen, J.M.; Buford, T.W.; Fields, C.J.; Woods, J.A. Exercise and the Gut Microbiome: A Review of the Evidence, Potential Mechanisms, and Implications for Human Health. Exerc. Sport Sci. Rev. 2019, 47, 75–85.
  66. Mohr, A.E.; Jäger, R.; Carpenter, K.C.; Kerksick, C.M.; Purpura, M.; Townsend, J.R.; West, N.P.; Black, K.; Gleeson, M.; Pyne, D.B.; et al. The athletic gut microbiota. J. Int. Soc. Sports Nutr. 2020, 17, 1–33.
  67. Evans, C.C.; LePard, K.J.; Kwak, J.W.; Stancukas, M.C.; Laskowski, S.; Dougherty, J.; Moulton, L.; Glawe, A.; Wang, Y.; Leone, V.; et al. Exercise Prevents Weight Gain and Alters the Gut Microbiota in a Mouse Model of High Fat Diet-Induced Obesity. PLoS ONE 2014, 9, e92193.
  68. Denou, E.; Marcinko, K.; Surette, M.G.; Steinberg, G.R.; Schertzer, J.D. High-intensity exercise training increases the diversity and metabolic capacity of the mouse distal gut microbiota during diet-induced obesity. Am. J. Physiol. Endocrinol. Metab. 2016, 310, E982–E993.
  69. Clarke, S.; Murphy, E.F.; O’Sullivan, O.; Lucey, A.; Humphreys, M.; Hogan, A.; Hayes, P.; O’Reilly, M.; Jeffery, I.; Wood-Martin, R.; et al. Exercise and associated dietary extremes impact on gut microbial diversity. Gut 2014, 63, 1913–1920.
  70. Aoki, T.; Oyanagi, E.; Watanabe, C.; Kobiki, N.; Miura, S.; Yokogawa, Y.; Kitamura, H.; Teramoto, F.; Kremenik, M.J.; Yano, H. The Effect of Voluntary Exercise on Gut Microbiota in Partially Hydrolyzed Guar Gum Intake Mice under High-Fat Diet Feeding. Nutrients 2020, 12, 2508.
  71. Xiao, S.; Fei, N.; Pang, X.; Shen, J.; Wang, L.; Zhang, B.; Zhang, M.; Zhang, X.; Zhang, C.; Li, M.; et al. A gut microbiota-targeted dietary intervention for amelioration of chronic inflammation underlying metabolic syndrome. FEMS Microbiol. Ecol. 2014, 87, 357–367.
  72. Shondelmyer, K.; Knight, R.; Sanivarapu, A.; Ogino, S.; Vanamala, J.K.P. Ancient Thali Diet: Gut Microbiota, Immunity, and Health. Yale J. Biol. Med. 2018, 91, 177–184.
  73. Lira, F.S.; Rosa, J.C.; Pimentel, G.D.; Souza, H.A.; Caperuto, E.C.; CarnevaliJr, L.C.; Seelaender, M.; Damaso, A.R.; Oyama, L.M.; de Mello, M.T.; et al. Endotoxin levels correlate positively with a sedentary lifestyle and negatively with highly trained subjects. Lipids Health Dis. 2010, 9, 82.
  74. Kallio, K.A.E.; Hätönen, K.A.; Lehto, M.; Salomaa, V.; Männistö, S.; Pussinen, P.J. Endotoxemia, nutrition, and cardiometabolic disorders. Acta Diabetol. 2015, 52, 395–404.
  75. Liu, Z.; Liu, H.-Y.; Zhou, H.; Zhan, Q.; Lai, W.; Zeng, Q.; Ren, H.; Xu, D. Moderate-Intensity Exercise Affects Gut Microbiome Composition and Influences Cardiac Function in Myocardial Infarction Mice. Front. Microbiol. 2017, 8, 1687.
  76. Lustgarten, M.S. The Role of the Gut Microbiome on Skeletal Muscle Mass and Physical Function: 2019 Update. Front. Physiol. 2019, 10, 1435.
  77. Ortiz-Alvarez, L.; Xu, H.; Martinez-Tellez, B. Influence of Exercise on the Human Gut Microbiota of Healthy Adults: A Systematic Review. Clin. Transl. Gastroenterol. 2020, 11, e00126.
  78. Li, J.; Lin, S.; Vanhoutte, P.M.; Woo, C.W.; Xu, A. Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe-/- Mice. Circulation 2016, 133, 2434–2446.
  79. Depommier, C.; Everard, A.; Druart, C.; Plovier, H.; Van Hul, M.; Vieira-Silva, S.; Falony, G.; Raes, J.; Maiter, D.; Delzenne, N.M.; et al. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: A proof-of-concept exploratory study. Nat. Med. 2019, 25, 1096–1103.
  80. Ponziani, F.R.; Zocco, M.A.; D’Aversa, F.; Pompili, M.; Gasbarrini, A. Eubiotic properties of rifaximin: Disruption of the traditional concepts in gut microbiota modulation. World J. Gastroenterol. 2017, 23, 4491–4499.
  81. Conraads, V.M.; Jorens, P.G.; De Clerck, L.S.; Van Saene, H.K.; Ieven, M.M.; Bosmans, J.M.; Schuerwegh, A.; Bridts, C.H.; Wuyts, F.; Stevens, W.J.; et al. Selective intestinal decontamination in advanced chronic heart failure: A pilot trial. Eur. J. Heart Fail. 2004, 6, 483–491.
  82. Ridker, P.M.; Everett, B.M.; Thuren, T.; MacFadyen, J.G.; Chang, W.H.; Ballantyne, C.; Fonseca, F.; Nicolau, J.; Koenig, W.; Anker, S.D.; et al. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N. Engl. J. Med. 2017, 377, 1119–1131.
  83. Jia, Q.; Li, H.; Zhou, H.; Zhang, X.; Zhang, A.; Xie, Y.; Li, Y.; Lv, S.; Zhang, J. Role and Effective Therapeutic Target of Gut Microbiota in Heart Failure. Cardiovasc. Ther. 2019, 2019, 5164298.
  84. Kumar, S.A.; Ward, L.C.; Brown, L. Inulin oligofructose attenuates metabolic syndrome in high-carbohydrate, high-fat diet-fed rats. Br. J. Nutr. 2016, 116, 1502–1511.
  85. Alonso, A.; de la Fuente, C.; Martín-Arnau, A.M.; de Irala, J.; Martínez, J.A.; Martínez-González, M. Fruit and vegetable consumption is inversely associated with blood pressure in a Mediterranean population with a high vegetable-fat intake: The Seguimiento Universidad de Navarra (SUN) Study. Br. J. Nutr. 2004, 92, 311–319.
  86. Sureda, A.; Del Mar Bibiloni, M.; Julibert, A.; Bouzas, C.; Argelich, E.; Llompart, I.; Pons, A.; Tur, J.A. Adherence to the Mediterranean Diet and Inflammatory Markers. Nutrients 2018, 10, 62.
  87. Saneei, P.; Hashemipour, M.; Kelishadi, R.; Esmaillzadeh, A. The Dietary Approaches to Stop Hypertension (DASH) Diet Affects Inflammation in Childhood Metabolic Syndrome: A Randomized Cross-Over Clinical Trial. Ann. Nutr. Metab. 2014, 64, 20–27.
  88. Phillips, C.M.; Harrington, J.M.; Perry, I.J. Relationship between dietary quality, determined by DASH score, and cardiometabolic health biomarkers: A cross-sectional analysis in adults. Clin. Nutr. 2019, 38, 1620–1628.
  89. Aguilar, E.C.; Leonel, A.J.; Teixeira, L.G.; Silva, A.R.; Silva, J.F.; Pelaez, J.M.N.; Capettini, L.S.A.; Lemos, V.S.; Santos, R.A.S.; Alvarez-Leite, J.I. Butyrate impairs atherogenesis by reducing plaque inflammation and vulnerability and decreasing NFκB activation. Nutr. Metab. Cardiovasc. Dis. 2014, 24, 606–613.
  90. Aguilar, E.C.; dos Santos, L.C.; Leonel, A.J.; de Oliveira, J.S.; Santos, E.A.; Navia-Pelaez, J.M.; da Silva, J.F.; Mendes, B.P.; Capettini, L.S.; Teixeira, L.G.; et al. Oral butyrate reduces oxidative stress in atherosclerotic lesion sites by a mechanism involving NADPH oxidase down-regulation in endothelial cells. J. Nutr. Biochem. 2016, 34, 99–105.
  91. Wang, L.; Zhu, Q.; Lu, A.; Liu, X.; Zhang, L.; Xu, C.; Liu, X.; Li, H.; Yang, T. Sodium butyrate suppresses angiotensin II-induced hypertension by inhibition of renal (pro)renin receptor and intrarenal renin–angiotensin system. J. Hypertens. 2017, 35, 1899–1908.
  92. Kasahara, K.; Krautkramer, K.A.; Org, E.; Romano, K.A.; Kerby, R.L.; Vivas, E.I.; Mehrabian, M.; Denu, J.M.; Bäckhed, F.; Lusis, A.J.; et al. Interactions between Roseburia intestinalis and diet modulate atherogenesis in a murine model. Nat. Microbiol. 2018, 3, 1461–1471.
  93. Tang, W.H.W.; Bäckhed, F.; Landmesser, U.; Hazen, S.L. Intestinal Microbiota in Cardiovascular Health and Disease: JACC State-of-the-Art Review. J. Am. Coll Cardiol. 2019, 73, 2089–2105.
  94. Furusawa, Y.; Obata, Y.; Fukuda, S.; Endo, T.A.; Nakato, G.; Takahashi, D.; Nakanishi, Y.; Uetake, C.; Kato, K.; Kato, T.; et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 2013, 504, 446–450.
  95. Frost, G.; Sleeth, M.L.; Sahuri-Arisoylu, M.; Lizarbe, B.; Cerdan, S.; Brody, L.; Anastasovska, J.; Ghourab, S.; Hankir, M.; Zhang, S.; et al. The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nat. Commun. 2014, 5, 3611.
  96. Tang, W.W.; Wang, Z.; Shrestha, K.; Borowski, A.G.; Wu, Y.; Troughton, R.W.; Klein, A.L.; Hazen, S.L. Intestinal Microbiota-Dependent Phosphatidylcholine Metabolites, Diastolic Dysfunction, and Adverse Clinical Outcomes in Chronic Systolic Heart Failure. J. Card. Fail. 2015, 21, 91–96.
  97. Gibson, G.R.; Hutkins, R.; Sanders, M.E.; Prescott, S.L.; Reimer, R.A.; Salminen, S.J.; Scott, K.; Stanton, C.; Swanson, K.S.; Cani, P.D.; et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat. Rev. Gastroenterol. Hepatol. 2017, 14, 491–502.
  98. De Filippis, F.; Pellegrini, N.; Vannini, L.; Jeffery, I.B.; La Storia, A.; Laghi, L.; Serrazanetti, D.I.; Di Cagno, R.; Ferrocino, I.; Lazzi, C.; et al. High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome. Gut 2016, 65, 1812–1821.
  99. Naqvi, S.; Asar, T.O.; Kumar, V.; Al-Abbasi, F.A.; Alhayyani, S.; Kamal, M.A.; Anwar, F. A cross-talk between gut microbiome, salt and hypertension. Biomed. Pharmacother. 2021, 134, 111156.
  100. Den Besten, G.; Bleeker, A.; Gerding, A.; van Eunen, K.; Havinga, R.; van Dijk, T.H.; Oosterveer, M.H.; Jonker, J.W.; Groen, A.K.; Reijngoud, D.J.; et al. Short-Chain Fatty Acids Protect Against High-Fat Diet-Induced Obesity via a PPARγ-Dependent Switch from Lipogenesis to Fat Oxidation. Diabetes 2015, 64, 2398–2408.
  101. Miura, K.; Greenland, P.; Stamler, J.; Liu, K.; Daviglus, M.L.; Nakagawa, H. Relation of Vegetable, Fruit, and Meat Intake to 7-Year Blood Pressure Change in Middle-aged Men: The Chicago Western Electric Study. Am. J. Epidemiology 2004, 159, 572–580.
  102. Bartolomaeus, H.; Balogh, A.; Yakoub, M.; Homann, S.; Markó, L.; Höges, S.; Tsvetkov, D.; Krannich, A.; Wundersitz, S.; Avery, E.G.; et al. Short-Chain Fatty Acid Propionate Protects From Hypertensive Cardiovascular Damage. Circulation 2019, 139, 1407–1421.
  103. Catry, E.; Bindels, L.B.; Tailleux, A.; Lestavel, S.; Neyrinck, A.M.; Goossens, J.-F.; Lobysheva, I.; Plovier, H.; Essaghir, A.; Demoulin, J.-B.; et al. Targeting the Gut Microbiota with Inulin-Type Fructans: Preclinical Demonstration of a Novel Approach in the Management of Endothelial Dysfunction. Gut 2018, 67, 271–283.
  104. Jin, M.; Qian, Z.; Yin, J.; Xu, W.; Zhou, X. The role of intestinal microbiota in cardiovascular disease. J. Cell. Mol. Med. 2019, 23, 2343–2350.
  105. Lindskog Jonsson, A.; Caesar, R.; Akrami, R.; Reinhardt, C.; Fåk Hållenius, F.; Borén, J.; Bäckhed, F. Impact of Gut Microbiota and Diet on the Development of Atherosclerosis in Apoe -/- Mice. Arterioscler. Thromb. Vasc. Biol. 2018, 38, 2318–2326.
  106. Wang, Z.; Bergeron, N.; Levison, B.S.; Li, X.S.; Chiu, S.; Jia, X.; Koeth, R.A.; Li, L.; Wu, Y.; Tang, W.H.W.; et al. Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women. Eur. Heart J. 2019, 40, 583–594.
  107. Korcz, E.; Kerényi, Z.; Varga, L. Dietary fibers, prebiotics, and exopolysaccharides produced by lactic acid bacteria: Potential health benefits with special regard to cholesterol-lowering effects. Food Funct. 2018, 9, 3057–3068.
  108. Lew, L.C.; Choi, S.B.; Khoo, B.Y.; Sreenivasan, S.; Ong, K.L.; Liong, M.T. Lactobacillus plantarum DR7 Reduces Cholesterol via Phosphorylation of AMPK That Down-regulated the mRNA Expression of HMG-CoA Reductase. Korean J. Food Sci. Anim. Resour. 2018, 38, 350.
  109. Ojetti, V.; Lauritano, E.C.; Barbaro, F.; Migneco, A.; Ainora, M.E.; Fontana, L.; Gabrielli, M.; Gasbarrini, A. Rifaximin pharmacology and clinical implications. Expert Opin. Drug Metab. Toxicol. 2009, 5, 675–682.
  110. Delzenne, N.M.; Neyrinck, A.M.; Bäckhed, F.; Cani, P.D. Targeting gut microbiota in obesity: Effects of prebiotics and probiotics. Nat. Rev. Endocrinol. 2011, 7, 639–646.
  111. Al Khodor, S.; Reichert, B.; Shatat, I.F. The Microbiome and Blood Pressure: Can Microbes Regulate Our Blood Pressure? Front Pediatr. 2017, 5, 1.
  112. A Petriz, B.; Castro, A.P.; Almeida, J.A.; Gomes, C.P.; Fernandes, G.R.; Kruger, R.H.; Pereira, R.W.; Franco, O.L. Exercise induction of gut microbiota modifications in obese, non-obese and hypertensive rats. BMC Genom. 2014, 15, 1–13.
  113. Lambert, J.E.; Myslicki, J.P.; Bomhof, M.R.; Belke, D.D.; Shearer, J.; Reimer, R.A. Exercise training modifies gut microbiota in normal and diabetic mice. Appl. Physiol. Nutr. Metab. 2015, 40, 749–752.
  114. Allen, J.M.; Mailing, L.J.; Niemiro, G.M.; Moore, R.; Cook, M.D.; White, B.A.; Holscher, H.D.; Woods, J.A. Exercise Alters Gut Microbiota Composition and Function in Lean and Obese Humans. Med. Sci. Sports Exerc. 2018, 50, 747–757.
  115. Cerdá, B.; Pérez, M.; Pérez-Santiago, J.D.; Tornero-Aguilera, J.F.; González-Soltero, R.; Larrosa, M. Gut microbiota modification: Another piece in the puzzle of the benefits of physical exercise in health? Front Physiol. 2016, 18, 51.
  116. Yan, Q.; Zhai, W.; Yang, C.; Li, Z.; Mao, L.; Zhao, M.; Wu, X. The Relationship among Physical Activity, Intestinal Flora, and Cardiovascular Disease. Cardiovasc. Ther. 2021, 2021, 1–10.
  117. Pant, K.; Peixoto, E.; Richard, S.; Gradilone, S.A. Role of Histone Deacetylases in Carcinogenesis: Potential Role in Cholangiocarcinoma. Cells 2020, 9, 780.
  118. Ahmad, A.F.; Ward, N.; Dwivedi, G. The gut microbiome and heart failure. Curr. Opin. Cardiol. 2019, 34, 225–232.
  119. Huang, C.-C.; Lin, W.-T.; Hsu, F.-L.; Tsai, P.-W.; Hou, C.-C. Metabolomics investigation of exercise-modulated changes in metabolism in rat liver after exhaustive and endurance exercises. Eur. J. Appl. Physiol. 2009, 108, 557–566.
  120. Ganesh, B.; Nelson, J.W.; Eskew, J.R.; Ganesan, A.; Ajami, N.J.; Petrosino, J.F.; BryanJr, R.M.; Durgan, D.J. Prebiotics, Probiotics, and Acetate Supplementation Prevent Hypertension in a Model of Obstructive Sleep Apnea. Hypertension 2018, 72, 1141–1150.
  121. Ohira, H.; Tsutsui, W.; Fujioka, Y. Are Short Chain Fatty Acids in Gut Microbiota Defensive Players for Inflammation and Atherosclerosis? J. Atheroscler. Thromb. 2017, 24, 660.
  122. Vinolo, M.A.R.; Rodrigues, H.G.; Festuccia, W.T.; Crisma, A.R.; Alves, V.S.; Martins, A.R.; Amaral, C.L.; Fiamoncini, J.; Hirabara, S.M.; Sato, F.T.; et al. Tributyrin attenuates obesity-associated inflammation and insulin resistance in high-fat-fed mice. Am. J. Physiol. Endocrinol. Metab. 2012, 303, E272–E282.
  123. Martin, F.-P.; Wang, Y.; Sprenger, N.; Yap, I.K.S.; Lundstedt, T.; Lek, P.; Rezzi, S.; Ramadan, Z.; Van Bladeren, P.; Fay, L.B.; et al. Probiotic modulation of symbiotic gut microbial–host metabolic interactions in a humanized microbiome mouse model. Mol. Syst. Biol. 2008, 4, 157.
  124. Papadaki, A.; Martinez-Gonzalez, M.A.; Alonso-Gómez, A.; Rekondo, J.; Salas-Salvadó, J.; Corella, D.; Ros, E.; Fitó, M.; Estruch, R.; Lapetra, J.; et al. Mediterranean diet and risk of heart failure: Results from the PREDIMED randomized controlled trial. Eur. J. Heart Fail. 2017, 19, 1179–1185.
  125. Estruch, R.; Ros, E.; Salas-Salvadó, J.; Covas, M.-I.; Corella, D.; Arós, F.; Gómez-Gracia, E.; Ruiz-Gutiérrez, V.; Fiol, M.; Lapetra, J.; et al. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts. N. Engl. J. Med. 2018, 378, e34.
  126. Koeth, R.A.; Wang, Z.; Levison, B.S.; Buffa, J.A.; Org, E.; Sheehy, B.T.; Britt, E.B.; Fu, X.; Wu, Y.; Li, L.; et al. Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat. Med. 2013, 19, 576–585.
  127. Zhu, W.; Wang, Z.; Tang, W.H.W.; Hazen, S.L. Gut Microbe-Generated TMAO from Dietary Choline Is Prothrombotic in Subjects. Circulation 2017, 135, 1671.
  128. Li, Q.; Wu, T.; Liu, R.; Zhang, M.; Wang, R. Soluble Dietary Fiber Reduces Trimethylamine Metabolism via Gut Microbiota and Co-Regulates Host AMPK Pathways. Mol. Nutr. Food Res. 2017, 61, 1700473.
  129. Hamaya, R.; Ivey, K.L.; Lee, D.H.; Wang, M.; Li, J.; Franke, A.; Sun, Q.; Rimm, E.B. Association of diet with circulating trimethylamine-N-oxide concentration. Am. J. Clin. Nutr. 2020, 112, 1448–1455.
  130. Park, J.E.; Miller, M.; Rhyne, J.; Wang, Z.; Hazen, S.L. Differential effect of short-term popular diets on TMAO and other cardio-metabolic risk markers. Nutr. Metab. Cardiovasc. Dis. 2019, 29, 513–517.
  131. Wu, W.-K.; Chen, C.-C.; Liu, P.-Y.; Panyod, S.; Liao, B.-Y.; Chen, P.-C.; Kao, H.-L.; Kuo, H.-C.; Kuo, C.-H.; Chiu, T.H.T.; et al. Identification of TMAO-producer phenotype and host–diet–gut dysbiosis by carnitine challenge test in human and germ-free mice. Gut 2019, 68, 1439–1449.
  132. Brunt, V.E.; Casso, A.G.; Gioscia-Ryan, R.A.; Sapinsley, Z.J.; Ziemba, B.P.; Clayton, Z.S.; Bazzoni, A.E.; VanDongen, N.S.; Richey, J.J.; Hutton, D.A.; et al. Gut Microbiome-Derived Metabolite Trimethylamine N-Oxide Induces Aortic Stiffening and Increases Systolic Blood Pressure with Aging in Mice and Humans. Hypertension 2021, 78, 499–511.
  133. Tang, W.H.W.; Wang, Z.; Levison, B.S.; Koeth, R.A.; Britt, E.B.; Fu, X.; Wu, Y.; Hazen, S.L. Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk. N. Engl. J. Med. 2013, 368, 1575–1584.
  134. Wang, Z.; Tang, W.H.W.; Buffa, J.A.; Fu, X.; Britt, E.B.; Koeth, R.A.; Levison, B.; Fan, Y.; Wu, Y.; Hazen, S.L. Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide. Eur. Heart J. 2014, 35, 904–910.
  135. Brunt, V.E.; Gioscia-Ryan, R.A.; Richey, J.J.; Zigler, M.C.; Cuevas, L.M.; Gonzalez, A.; Vázquez-Baeza, Y.; Battson, M.L.; Smithson, A.T.; Gilley, A.D.; et al. Suppression of the gut microbiome ameliorates age-related arterial dysfunction and oxidative stress in mice. J. Physiol. 2019, 597, 2361–2378.
  136. Zhu, W.; Gregory, J.C.; Org, E.; Buffa, J.A.; Gupta, N.; Wang, Z.; Li, L.; Fu, X.; Wu, Y.; Mehrabian, M.; et al. Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk. Cell 2016, 165, 111–124.
  137. Rogers, M.A.M.; Aronoff, D.M. The influence of non-steroidal anti-inflammatory drugs on the gut microbiome. Clin. Microbiol. Infect. 2016, 22, 178.e1–178.e9.
  138. Wang, Z.; Roberts, A.B.; Buffa, J.A.; Levison, B.S.; Zhu, W.; Org, E.; Gu, X.; Huang, Y.; Zamanian-Daryoush, M.; Culley, M.K.; et al. Non-lethal Inhibition of Gut Microbial Trimethylamine Production for the Treatment of Atherosclerosis. Cell 2015, 163, 1585–1595.
  139. Craciun, S.; Balskus, E.P. Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme. Proc. Natl. Acad. Sci. USA 2012, 109, 21307–21312.
  140. Zhu, Y.; Jameson, E.; Crosatti, M.; Schäfer, H.; Rajakumar, K.; Bugg, T.D.H.; Chen, Y. Carnitine metabolism to trimethylamine by an unusual Rieske-type oxygenase from human microbiota. Proc. Natl. Acad. Sci. USA 2014, 111, 4268–4273.
  141. Brown, J.M.; Hazen, S.L. Targeting of microbe-derived metabolites to improve human health: The next frontier for drug discovery. J. Biol. Chem. 2017, 292, 8560–8568.
  142. Craciun, S.; Marks, J.A.; Balskus, E.P. Characterization of Choline Trimethylamine-Lyase Expands the Chemistry of Glycyl Radical Enzymes. ACS Chem. Biol. 2014, 9, 1408–1413.
  143. Xue, J.; Zhou, D.; Poulsen, O.; Imamura, T.; Hsiao, Y.-H.; Smith, T.H.; Malhotra, A.; Dorrestein, P.; Knight, R.; Haddad, G.G. Intermittent Hypoxia and Hypercapnia Accelerate Atherosclerosis, Partially via Trimethylamine-Oxide. Am. J. Respir. Cell Mol. Biol. 2017, 57, 581–588.
  144. Chen, K.; Zheng, X.; Feng, M.; Li, D.; Zhang, H. Gut Microbiota-Dependent Metabolite Trimethylamine N-Oxide Contributes to Cardiac Dysfunction in Western Diet-Induced Obese Mice. Front. Physiol. 2017, 8, 139.
  145. Roberts, A.; Gu, X.; Buffa, J.A.; Hurd, A.G.; Wang, Z.; Zhu, W.; Gupta, N.; Skye, S.M.; Cody, D.B.; Levison, B.S.; et al. Development of a gut microbe–targeted nonlethal therapeutic to inhibit thrombosis potential. Nat. Med. 2018, 24, 1407–1417.
  146. Andreesen, J.R. Glycine metabolism in anaerobes. Antonie Van Leeuwenhoek 1994, 66, 223–237.
  147. Pascal, M.-C.; Burini, J.-F.; Chippaux, M. Regulation of the trimethylamine N-oxide (TMAO) reductase in Escherichia coli: Analysis of tor::Mud1 operon fusion. Mol. Gen. Genet. 1984, 195, 351–355.
  148. Koeth, R.A.; Levison, B.S.; Culley, M.K.; Buffa, J.A.; Wang, Z.; Gregory, J.C.; Org, E.; Wu, Y.; Li, L.; Smith, J.D.; et al. γ-Butyrobetaine Is a Proatherogenic Intermediate in Gut Microbial Metabolism of L-Carnitine to TMAO. Cell Metab. 2014, 20, 799–812.
  149. Cashman, J.R.; Xiong, Y.; Lin, J.; Verhagen, H.; van Poppel, G.; van Bladeren, P.J.; Larsen-Su, S.; Williams, D.E. In vitro and in vivo inhibition of human flavin-containing monooxygenase form 3 (FMO3) in the presence of dietary indoles. Biochem. Pharmacol. 1999, 58, 1047–1055.
  150. Mitchell, S.C.; Smith, R.L. Trimethylaminuria: The fish malodor syndrome. Drug Metab. Dispos. 2001, 29, 517–521.
  151. Velasquez, M.T.; Ramezani, A.; Manal, A.; Raj, D.S. Trimethylamine N-Oxide: The Good, the Bad and the Unknown. Toxins 2016, 8, 326.
  152. Chittim, C.L.; Del Campo, A.M.; Balskus, E.P. Gut bacterial phospholipase Ds support disease-associated metabolism by generating choline. Nat. Microbiol. 2019, 4, 155–163.
  153. Chen, Y.-S.; Liu, H.-M.; Lee, T.-Y. Ursodeoxycholic Acid Regulates Hepatic Energy Homeostasis and White Adipose Tissue Macrophages Polarization in Leptin-Deficiency Obese Mice. Cells 2019, 8, 253.
  154. Úbeda, M.; Lario, M.; Muñoz, L.; Borrero, M.J.; Rodríguez-Serrano, M.; Sánchez-Díaz, A.M.; Del Campo, R.; Lledó, L.; Pastor, Ó.; García-Bermejo, L.; et al. Obeticholic acid reduces bacterial translocation and inhibits intestinal inflammation in cirrhotic rats. J. Hepatol. 2016, 64, 1049–1057.
  155. Pellicciari, R.; Costantino, G.; Camaioni, E.; Sadeghpour, B.M.; Entrena, A.; Willson, T.M.; Fiorucci, S.; Clerici, C.; Gioiello, A. Bile acid derivatives as ligands of the farnesoid X receptor. Synthesis, evaluation, and structure-activity relationship of a series of body and side chain modified analogues of chenodeoxycholic acid. J. Med. Chem. 2004, 47, 4559–4569.
  156. Eblimit, Z.; Thevananther, S.; Karpen, S.J.; Taegtmeyer, H.; Moore, D.D.; Adorini, L.; Penny, D.J.; Desai, M.S. TGR5 activation induces cytoprotective changes in the heart and improves myocardial adaptability to physiologic, inotropic, and pressure-induced stress in mice. Cardiovasc. Ther. 2018, 36, e12462.
  157. Joyce, S.A.; MacSharry, J.; Casey, P.G.; Kinsella, M.; Murphy, E.F.; Shanahan, F.; Hill, C.; Gahan, C.G.M. Regulation of host weight gain and lipid metabolism by bacterial bile acid modification in the gut. Proc. Natl. Acad. Sci. USA 2014, 111, 7421–7426.
  158. Korpela, K.; Salonen, A.; Virta, L.J.; Kekkonen, R.A.; Forslund, K.; Bork, P.; De Vos, W.M. Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children. Nat. Commun. 2016, 7, 10410.
  159. Caparrós-Martín, J.A.; Lareu, R.R.; Ramsay, J.P.; Peplies, J.; Reen, F.J.; Headlam, H.A.; Ward, N.C.; Croft, K.D.; Newsholme, P.; Hughes, J.D.; et al. Statin Therapy Causes Gut Dysbiosis in Mice through a PXR-Dependent Mechanism. Microbiome 2017, 5, 95.
  160. Williams, B.B.; Van Benschoten, A.H.; Cimermancic, P.; Donia, M.S.; Zimmermann, M.; Taketani, M.; Ishihara, A.; Kashyap, P.C.; Fraser, J.S.; Fischbach, M.A. Discovery and Characterization of Gut Microbiota Decarboxylases that Can Produce the Neurotransmitter Tryptamine. Cell Host Microbe 2014, 16, 495–503.
  161. Pott, A.S.; Dahl, C. Sirohaem sulfite reductase and other proteins encoded by genes at the dsr locus of Chromatium vinosum are involved in the oxidation of intracellular sulfur. Microbiology 1998, 144, 1881–1894.
  162. London, J.; Goldberg, M.E. The Tryptophanase from Escherichia coli K-12: I. Purification, Physical Properties, and Quaternary Structure. J. Biol. Chem. 1972, 10, 1566–1570.
  163. Peck, S.C.; Denger, K.; Burrichter, A.; Irwin, S.M.; Balskus, E.P.; Schleheck, D. A glycyl radical enzyme enables hydrogen sulfide production by the human intestinal bacterium Bilophila wadsworthia. Proc. Natl. Acad. Sci. USA 2019, 116, 3171–3176.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Pharmacology & Pharmacy
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Yahkub Babatunde Mutalub
,
Monsurat Abdulwahab
,
Alkali Mohammed
,
Aishat Mutalib Yahkub
,
Sameer Badri AL-Mhanna
,
Wardah Yusof
,
Suk Peng Tang
,
Aida Hanum Ghulam Rasool
,
Siti Safiah Mokhtar
View Times: 506
Entry Collection: Hypertension and Cardiovascular Diseases
Revisions: 2 times (View History)
Update Date: 09 Sep 2022
Table of Contents
    1000/1000
    Hot Most Recent
    Video Production Service
    Feedback