Microbiome-Directed Therapies: History
View Latest Version
Please note this is an old version of this entry, which may differ significantly from the current revision.
Contributor:
Shiyue He
,
Fengyu Lin
,
Xinyue Hu
,
Pinhua Pan

Loss of commensal microbiota and excessive growth of potentially pathogenic bacteria are the main features of the gut microbiota in critically ill adult patients. Gut microbiota imbalance can increase the risk of secondary infection, immunosuppression, and even organ dysfunction, leading to an increased incidence of opportunistic infections and sepsis, aggravated various target organ damage, and worsened patient condition. Additionally, even after recovery from sepsis, the slow recolonization of patients’ normal microbiota may lead to long-term immunosuppression and poor prognosis. Therefore, different strategies related to the gut microbiota, such as using probiotics and prebiotics alone or in combination (synthetic preparations,) have been proposed in order to prevent the further growth of pathogens and improve the outcomes of critically ill patients.

  • gut microbiota
  • critically ill patients
  • fecal microbiota transplantation

1. Probiotics

The International Scientific Association for Probiotics and Prebiotics defines probiotics as “live microorganisms that, when given in sufficient amounts, have a beneficial effect on the health of the host” [1]. They protect the intestinal barrier, attenuate pathogen overgrowth, decrease bacterial translocation, reduce serum pro-inflammatory cytokine concentrations while increasing the serum anti-inflammatory cytokine concentrations, and induce host immunomodulation to prevent infection [2][3][4][5]. In addition, probiotics also act through pharmacokinetics. For example, gut Actinobacterium Eggerthella lenta could affect the pharmacokinetic of digoxin and reduce its toxicity in treating congestive heart failure [6]. Moreover, the probiotic E. coli strain Nissle 1917 influences the pharmacokinetics of the antiarrhythmic amiodarone and increases drug absorption [7].
Several probiotics play a role in adult intensive care [8]. Probiotic therapy significantly reduces the incidence of diarrhea, acquired infections, and VAP in critically ill patients [9][10][11]. In sepsis-induced, severe ALI, Akkermansia muciniphila (A. muciniphila) was significantly negatively correlated with TNF-α, IL-1β and IL-6, suggesting that Gut A. muciniphila plays an important role in ALI and that supplementation with A. muciniphila may be a possible therapy for ALI [12]. In addition, the combination of probiotics Bifidobacterium longum, Lactobacillus bulgaricus and Streptococcus thermophilus was more effective as an adjuvant therapy for severe and critically ill patients with COVID-19, shortening the nucleic acid conversion time, and reducing the inflammatory index such as procalcitonin and C-reactive protein [13]. Another probiotic, L. reuteri., can reduce lung inflammation and mortality of ARDS [14]. In uremic dialysis patients, oral administration of Lactobacillus acidophilus led to a decrease in serum dimethylamine, a potential uremic toxin [15]. The administration of probiotics (e.g., Bifidobacterium bifidum, Bifidobacterium catenulatum, Bifidobacterium longum, Lactobacillus plantarum) can also significantly reduce serum proinflammatory endotoxin, decrease cytokine levels, and improve life quality [16]. A double-blind clinical study has shown that the probiotics Lactobacillus rhamnosus GG or a combination application of probiotics (including streptococcus thermophiles, lactobacillus acidophilus, lactobacillus delbrueckii ssp. bulgaricus, lactobacillus paracasei, lactobacillus plantarum, Bifidobacterium longum, Bifidobacterium infantis, and Bifidobacterium breve) has beneficial effects on heart failure caused by adverse cardiac remodeling after myocardial infarction (MI). These probiotics play roles through decreasing the levels of intestinal metabolite trimethylamine N-oxide (TMAO) [17][18].

2. Prebiotics

Prebiotics are substrates that can be selectively utilized by host microbes to maintain gut homeostasis and improve health outcomes. Dietary fiber (DF) is a powerful beneficial prebiotic that promotes the production of SCFAs [19].
Several prospective cohort studies have found that the use of DF in critically ill patients is effective in enhancing intestinal barrier function, reducing the systemic inflammatory response, modulating gut microbiota: increasing the abundance of the SCFAs-producing bacteria, and decreasing the level of potentially pathogenic microbiota [20]. The use of DF also improves the clinical outcomes, shortening hospital days, and reducing morbidity and mortality in critically ill patients [20]. Researchers have also found that prebiotics may ameliorate the prognosis of COVID-19 by offering anti-inflammatory nutrition, improving malnutrition, and enhancing immunity through the gut–lung microbial axis [21][22][23]. More importantly, DF-fermented SCFAs increase the production of CD103+DCs, promote the differentiation of activated CD8+T cells to effector cells with a memory phenotype, and improve the outcomes of anti-PD-1 immune checkpoint inhibitor therapy in patients with melanoma [24][25]. Similarly, the SCFAs produced by DF provide energy to the gut microbiota and promote the amino acids to reach the colon for absorption into the body rather than fermenting into uremic solutes [26].
In addition, flavonoid is an important class of natural products widely found in fruits which belongs to a class of plant secondary metabolites [27]. Clinical trials have demonstrated that flavonoids can upregulate the abundance of probiotics, such as Bifidobaterium and Lactobacillus, while downregulating the abundance of some pathogenic bacteria such as Staphylococcus aureus and Clostridium histolyticum [28][29]. Moreover, flavonoids can also promote the production of SCFAs [30].

3. Synbiotics

Synbiotics are mixtures of probiotics and prebiotics that exert beneficial effects on the host in two main ways: enhancing the viability of probiotic microorganisms and providing specific health effects [31][32]. Probiotics stimulated by prebiotics could regulate the metabolic activity of the gut, maintain the intestinal biostructure, and promote the growth and multiplication of probiotics and its resistance to reactive oxygen species and bile salts/acids [33]. In addition, synbiotic agents modulate the innate and adaptive immune systems to reduce systemic inflammation and promote extraintestinal organ function [33][34]. Synbiotics lead to lower concentrations of adverse metabolites which results in significantly increased SCFAs levels, which may contribute to a positive effect on the host health [31].
A double-blinded controlled clinical trial demonstrates that a combination of antibiotic intervention led to a significant reduction in pharyngeal aspiration in critically ill patients and an increased level of patient consciousness [35]. In addition, for hospital-acquired infections in critically ill patients, synbiotics may be a safer and more effective way to reduce endotoxin and inflammatory markers in serum and the complications of sepsis [4][11]. Studies have shown that prophylactic synbiotics (e.g., Bifidobacterium breve strain Yakult combined with Lactobacillus casei strain Shiorta, and galactooligosaccharides) increases the number of probiotics (e.g., Bifidobacterium, Lactobacillus) in fecal bacteria and intestinal SCFA levels, especially acetate. These may modulate the gut microbiota and environment, and have preventive effects on the incidence of enterocolitis and VAP in sepsis patients [36]. Moreover, synbiotics are used to maintain a stable intestinal microbiota after SIRS and major surgery including high-risk hepatectomy, colorectal resection surgery, Roux-en-Y gastric bypass (RYGB), and sepsis-associated encephalitis (SAE) [37][38]. Synbiotics could also reduce the incidence of diseases such as VAP and healthcare-associated pneumonia, and shorten ICU length of stay [39][40]. In the late stage of intestinal disorders, supplementation with synbiotics can accelerate the recovery of the microbiota, thus preventing the development of sepsis and the onset and progression of critical diseases such as ARDS to some extent [41]. Synbiotics intake has been demonstrated to reduce plasma levels of uremic toxin and may exert nephroprotective effects [15].
Based on the above literature, the researchers briefly summarize the different scenarios in which FMT, SDD, probiotics, prebiotics, and synbiotics act directly by regulating the gut microbiota (Table 1).
Table 1. Appropriate situations for different therapeutic approaches.
Mirobiome-Based Therapeutics Appropriate Situations References
FMT Post-antibiotics; CDI; the possible eradication of colonization and recurrent infections due to different species of MDROs. [42][43][44]
SDD Wards with low rates of resistant bacteria; patients colonized with Staphylococcus aureus or aerobic gram-negative bacteria. [43][45]
Probiotics, prebiotics and synbiotics Available as food supplements; most situations with gut microbiota dysbiosis except post-antibiotics. [1][42]
FMT, fecal microbiota transplantation, SDD, selectively digestive decontamination, CDI, Clostridium difficile infection, MDROs, multidrug-resistant organisms.

4. Microbiota-Derived Metabolites and Proteins

Transfer of sterile filtrates from donor feces, rather than fecal microbiota, has been shown to be sufficient to restore normal bowel habits and eliminate symptoms [46]. Therefore, researchers speculate that gut metabolites may contribute to critical illness and dysbiosis. There is observational data that correlates critical illness, dysbiosis, and altered gut metabolites, including SCFAs, flavonoids, indole derivations, amines, bile acids, etc. [47]. In this section, several microbiota-derived metabolites and proteins therapies will be summarized.

4.1. Short-Chain Fatty Acid

Typically, undigested DF, as well as proteins and peptides, can be fermented by gut bacteria in the cecum and colon. The main products of these fermentative reactions are SCFAs, consisting of groups of fatty acids with less than six carbons. SCFAs include formic acid (C1), acetic acid (C2), propionic acid (C3), butyric acid (C4), and valeric acid (C5). The major SCFAs in the gut are C2, C3, and C4, accounting for more than 95% of all SCFAs [48]. SCFAs are key mediators in the regulation of myocardial tissue repair by gut microbiota [49]. Decreased microbiota abundance has been shown to alter immune cell responses to infectious damage, usually resulting in a pro-inflammatory phenotype [50], which further aggravates disease progression. Normal levels of SCFAs support the activity of innate lymphocytes, T cells, and B cells in the gut, thereby improving immune tolerance in the gut, strengthening the gut immune barrier, and enhancing its ability to clear pathogens [51][52]. Furthermore, a large proportion of gut-derived SCFAs are transported out of the gut to affect other organs through the gut–lung axis, gut–brain axis, gut–liver axis, gut–kidney axis, gut–bone axis, gut–skin axis, gut–fat axis, gut–heart axis, and so on [53][54][55][56][57][58]. Available studies have shown that gut microbiota dysbiosis and a lack of SCAFs are significantly associated with the severity of COVID-19 [59]. Therefore, maintaining healthy gut microbiota and normal levels of SCFAs contribute to critical illness prevention and prognosis. However, little is known about their therapeutic mechanism in critically ill patients, except for mouse models, so verifying the therapeutic mechanism of SCFAs in clinical trials may be a possible direction in subsequent research. In the following sections, the researchers introduce the beneficial role that major SCFAs play in critical illness.

Butyrate

Previous work on mouse models has shown that butyrate, a specific type of SCFAs readily produced from fiber-rich diets through microbial fermentation, is critical for the maintenance of intestinal homeostasis [60]. Thus, the researchers speculate that butyrate acid plays a crucial role in critically ill patients.
In a mouse model of sepsis-associated encephalitis, butyrate is a major metabolite of intestinal microbiota and may have a neuroprotective effect in the process of sepsis through the GPR109A/Nrf2/HO-1 pathway [61].
Butyrate acid promotes the proliferation and differentiation of intestinal epithelial cells (IECs) and the synthesis of intestinal epithelial tight junction protein, such as the increased expression of Zo-1 and Occludin, reduces cell apoptosis, and inhibits intestinal permeability, resulting in enhanced intestinal mucosa mechanical barrier function [62][63]. In addition, butyrate acid enhances the intestinal mucosal immune barrier. It can maintain immune homeostasis by restoring the IRF3 signaling pathway [64]. Moreover, butyrate acid promotes the production of anti-microbial peptides (AMPs) [65]. AMPs are small molecular peptides produced by IECs with broad-spectrum antimicrobial activities, such as butyrate acid which promotes RegIIIγ and β-defensins in a GPR43-dependent manner, which play important roles in limiting bacteria and manipulating species composition [66][67]. Furthermore, butyrate acid strengthens the intestinal biological barrier function. Elevated levels of butyrate acid lowers colonic PH and inhibits the growth and colonization of pathogenic bacteria [68]. It also prevents bacterial translocation across the intestinal barrier by promoting the antimicrobial activity of intestinal macrophages [69].
As a histone deacetylase inhibitor, it affects the gene expression profile of intestinal epithelial cells and immune cells through histone deacetylases [70][71][72]. It can alter the gene expression profile of immune cells such as Treg cells, intestinal macrophages, and bone marrow-derived macrophages through G protein-coupled receptors (GPCR), affecting their response to microbial stimulation [69][73]. Butyrate acid can relieve inflammation and clinical symptoms in critically ill patients by activating Treg cells [74]. In addition to directly affecting the function of the intestine itself, butyrate acid can also affect the organs via the gut–lung axis and gut–brain axis. Studies have shown that the GPCR overlap with each other in extraintestinal or intestinal organs [75]. For example, GPR109A viewed as GPCR common to both lung and intestine can be activated by butyrate [48]. Butyrate acid affects the intestinal epithelial barrier function and immune function regulation through GPR109A, with similar effects on lung tissue (Table 2). Intraperitoneal injection of sodium butyrate acid can decrease the expression of hypermobility protein 1 (HP-1), pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and inhibit the activation of the NF-κB signaling pathway in an ALI/ARDS mouse model [76][77].
Table 2. Association of G protein-coupled receptor with SCFAs.
GPCR Association with SCFAs References
GPR41 Activated by SCFAs such as propionate, butyrate and valerate.
SCFAs enhance the cellular metabolism and adaptive immunity function through GPR41 and maintain intestinal homeostasis. Propionate activated GPR41 alleviates inflammation in allergy.		 [78][79][80]
GPR43 GPR43 can be activated by SCFAs such as acetate, propionate, butyrate.
SCFAs promote intestinal epithelial cells to produce AMPs, stimulates the migration of neutrophils, and modulates the production of reactive oxygen species (ROS) and phagocytosis through a GPR43-relate manner. Elevated SCFAs level enhances luminal immunoglobulin A production and strengthen the intestinal mucosa barrier.		 [67][81][82][83][84][85]
GPR40 GPR40 receptor activation promotes tight junction assembly in airway epithelial cells via AMPK-dependent mechanisms. [86]
GPR109A Butyrate-mediated GPR109A activation suppresses inflammation and regulates lipid metabolism by regulating macrophages. [48][87][88]
GPCR/GPR, G protein-coupled receptor; SCFA, short-chain fatty acid; AMP, anti-microbiota peptide.

Propionate

Propionate is mainly produced by Bacteroides spp. and is used as a gluconeogenic substrate in the liver and intestinal to provide energy to the body [68]. Propionic acid is an anti-inflammatory cytokine, its level in serum may predict the severity and prognosis in critically ill patients and may be a cytokine regulatory marker for critical illnesses such as sepsis [89].

Acetate

Acetate is mainly derived from gut microbes and is a metabolite released into the intestinal lumen by anaerobic bacteria from the gut microbiota, which is then absorbed by IEC and distributed to peripheral capillaries [90]. In recent years, studies in mice have found that acetate inhibits the permeability of the alveolar–capillary barrier, reduces pulmonary edema, inhibits oxidative stress, suppresses inflammatory cell recruitment and inflammatory mediator production, and regulates MAPK pathway activation; thus leading to amelioration of ALI and ARDS [91]. Elevated levels of acetate may prevent IEC translocation by inhibiting endotoxin and increasing claudin, thereby reducing the incidence of sepsis [34][36][92].

4.2. Flavonoid Metabolites

Researchers have found that flavonoids ingested with food enter the circulatory system through the intestines to exert their beneficial effects [93]. Generally, flavonoids are absorbed as metabolites, and gut microbiota participate in this metabolism [94][95]. Flavonoid metabolites can shape the gut microbiota by inhibiting the growth of various pathogens and increasing beneficial genera; these could reduce the endotoxin, maintain gut immune homeostasis, and promote nutrients absorption [96][97]. Flavonoids metabolites have anti-inflammatory effects and play a part in local and systemic immunity. In mouse models, flavonoid metabolites can improve intestinal barrier function by reducing intestinal mucosal inflammation and maintaining the intestinal tight junction barrier and structure [98][99][100]. In addition, flavonoid metabolites regulate inflammatory mediators, such as through inhibiting endothelial activation, NLRP3 inflammasome, toll-like receptors (TLRs), or bromodomain-containing protein 4 (BRD4), as well as activating nuclear factor erythroid-derived 2-related factor 2 (Nrf2), thereby restoring cytokine storm in critical illness including SARS-CoV-2 infection [101]. DAT, a kind of flavonoid metabolite, has been shown to treat upper respiratory tract infections in mice and protect mice from bacterial endotoxin-induced septic shock [102][103]. Therefore, the researchers suggest that flavonoid metabolites produced by intestinal microbial metabolism play important roles when critically ill patients and hosts are infected with viruses and lethal bacterial infections.

4.3. Others

Other than SCFAs and flavonoid metabolites, other microbiota-derived metabolites and proteins also play a critical role in maintaining the balance of intestinal mucosa and contributing to the treatment of critical illness. Indole-3-propionic acid (IPA) could modulate gut microbiota in normal mice, increase the levels of some probiotics (e.g., Akkermansiaceae, Bifidobacteriaceae), strengthen the mucus barrier, and attenuate LPS-induced inflammatory factors in sepsis by increasing mucins and goblet cell secretion products [104]. Studies on mouse models of sepsis suggest that the anti-inflammatory activity of IPA may associated with the increased abundance of Bifidobacteriaceae and inhibited expansion of Enterobacteriaceae, contributing to an improvement in mortality in sepsis [105]. Aromatic microbial metabolites (AMMs), such as phenyl lactic and 4-hydroxyphenyllactic acids, have been observed at a much higher level than normal in the serum of septic patients [106]. A prospective observational pilot study found that high level of AMMs were associated with severity and mortality in critically ill patients, and may become a possible direction to improve the prognosis of critical illness [107]. TMAO has been found to be higher in individuals with heart failure than in controls, suggesting that TMAO is a new and novel risk factor in heart failure development and can lead to cardiac hypertrophy and cardiac fibrosis [108]. Beta-lactamase, produced primarily by extended-spectrum β-lactam Enterobacteriaceae, has been shown to reduce the jejunal concentration of antibiotics and to prevent antibiotics from reaching the colon, thus alleviating the effect of antibiotics on gut microbiota disturbance [109][110].

This entry is adapted from the peer-reviewed paper 10.3390/nu15224734

References

  1. 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.
  2. Manzanares, W.; Lemieux, M.; Langlois, P.L.; Wischmeyer, P.E. Probiotic and synbiotic therapy in critical illness: A systematic review and meta-analysis. Crit. Care 2016, 19, 262.
  3. Suez, J.; Zmora, N.; Segal, E.; Elinav, E. The pros, cons, and many unknowns of probiotics. Nat. Med. 2019, 25, 716–729.
  4. Seifi, N.; Sedaghat, A.; Nematy, M.; Khadem-Rezaiyan, M.; Shirazinezhad, R.; Ranjbar, G.; Safarian, M. Effects of synbiotic supplementation on the serum endotoxin level, inflammatory status, and clinical outcomes of adult patients with critical illness: A randomized controlled trial. Nutr. Clin. Pract. 2022, 37, 451–458.
  5. Milajerdi, A.; Mousavi, S.M.; Sadeghi, A.; Salari-Moghaddam, A.; Parohan, M.; Larijani, B.; Esmaillzadeh, A. The effect of probiotics on inflammatory biomarkers: A meta-analysis of randomized clinical trials. Eur. J. Nutr. 2020, 59, 633–649.
  6. Haiser, H.J.; Gootenberg, D.B.; Chatman, K.; Sirasani, G.; Balskus, E.P.; Turnbaugh, P.J. Predicting and manipulating cardiac drug inactivation by the human gut bacterium Eggerthella lenta. Science 2013, 341, 295–298.
  7. Matuskova, Z.; Anzenbacherova, E.; Vecera, R.; Tlaskalova-Hogenova, H.; Kolar, M.; Anzenbacher, P. Administration of a probiotic can change drug pharmacokinetics: Effect of E. coli Nissle 1917 on amidarone absorption in rats. PLoS ONE 2014, 9, e87150.
  8. Sudeep, K.C.; Angurana, S.K. Probiotic therapy in critical illness: Does it hold water? Intensive Care Med. 2021, 47, 922–923.
  9. Shimizu, K.; Hirose, T.; Ogura, H. Efficacy of probiotics in the prevention of diarrhea in ventilated critically ill ICU patients: Meta-analysis of randomized control trials. J. Intensive Care 2021, 9, 62.
  10. Batra, P.; Soni, K.D.; Mathur, P. Efficacy of probiotics in the prevention of VAP in critically ill ICU patients: An updated systematic review and meta-analysis of randomized control trials. J. Intensive Care 2020, 8, 81.
  11. Li, C.; Liu, L.; Gao, Z.; Zhang, J.; Chen, H.; Ma, S.; Liu, A.; Mo, M.; Wu, C.; Chen, D.; et al. Synbiotic Therapy Prevents Nosocomial Infection in Critically Ill Adult Patients: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials Based on a Bayesian Framework. Front. Med. 2021, 8, 693188.
  12. Wu, X.; Xuan, W.; Yang, X.; Liu, W.; Zhang, H.; Jiang, G.; Cao, B.; Jiang, Y. Ficolin A knockout alleviates sepsis-induced severe lung injury in mice by restoring gut Akkermansia to inhibit S100A4/STAT3 pathway. Int. Immunopharmacol. 2023, 121, 110548.
  13. Wang, H.; Wang, Y.; Lu, C.; Qiu, L.; Song, X.; Jia, H.; Cui, D.; Zhang, G. The efficacy of probiotics in patients with severe COVID-19. Ann. Palliat. Med. 2021, 10, 12374–12380.
  14. Alghetaa, H.; Mohammed, A.; Zhou, J.; Singh, N.; Nagarkatti, M.; Nagarkatti, P. Resveratrol-mediated attenuation of superantigen-driven acute respiratory distress syndrome is mediated by microbiota in the lungs and gut. Pharmacol. Res. 2021, 167, 105548.
  15. Rysz, J.; Franczyk, B.; Ławiński, J.; Olszewski, R.; Ciałkowska-Rysz, A.; Gluba-Brzózka, A. The Impact of CKD on Uremic Toxins and Gut Microbiota. Toxins 2021, 13, 252.
  16. Wang, I.K.; Wu, Y.Y.; Yang, Y.F.; Ting, I.W.; Lin, C.C.; Yen, T.H.; Chen, J.H.; Wang, C.H.; Huang, C.C.; Lin, H.C. The effect of probiotics on serum levels of cytokine and endotoxin in peritoneal dialysis patients: A randomised, double-blind, placebo-controlled trial. Benef. Microbes 2015, 6, 423–430.
  17. Moludi, J.; Saiedi, S.; Ebrahimi, B.; Alizadeh, M.; Khajebishak, Y.; Ghadimi, S.S. Probiotics Supplementation on Cardiac Remodeling Following Myocardial Infarction: A Single-Center Double-Blind Clinical Study. J. Cardiovasc. Transl. Res. 2021, 14, 299–307.
  18. Boutagy, N.E.; Neilson, A.P.; Osterberg, K.L.; Smithson, A.T.; Englund, T.R.; Davy, B.M.; Hulver, M.W.; Davy, K.P. Probiotic supplementation and trimethylamine-N-oxide production following a high-fat diet. Obesity 2015, 23, 2357–2363.
  19. Davani-Davari, D.; Negahdaripour, M.; Karimzadeh, I.; Seifan, M.; Mohkam, M.; Masoumi, S.J.; Berenjian, A.; Ghasemi, Y. Prebiotics: Definition, Types, Sources, Mechanisms, and Clinical Applications. Foods 2019, 8, 92.
  20. Fu, Y.; Moscoso, D.I.; Porter, J.; Krishnareddy, S.; Abrams, J.A.; Seres, D.; Chong, D.H.; Freedberg, D.E. Relationship Between Dietary Fiber Intake and Short-Chain Fatty Acid-Producing Bacteria During Critical Illness: A Prospective Cohort Study. J. Parenter. Enter. Nutr. 2020, 44, 463–471.
  21. Conte, L.; Toraldo, D.M. Targeting the gut-lung microbiota axis by means of a high-fibre diet and probiotics may have anti-inflammatory effects in COVID-19 infection. Ther. Adv. Respir. Dis. 2020, 14, 1753466620937170.
  22. Hawryłkowicz, V.; Lietz-Kijak, D.; Kaźmierczak-Siedlecka, K.; Sołek-Pastuszka, J.; Stachowska, L.; Folwarski, M.; Parczewski, M.; Stachowska, E. Patient Nutrition and Probiotic Therapy in COVID-19: What Do We Know in 2021? Nutrients 2021, 13, 3385.
  23. Gasmi, A.; Tippairote, T.; Mujawdiya, P.K.; Peana, M.; Menzel, A.; Dadar, M.; Benahmed, A.G.; Bjørklund, G. The microbiota-mediated dietary and nutritional interventions for COVID-19. Clin. Immunol. 2021, 226, 108725.
  24. Davar, D.; Zarour, H.M. Facts and Hopes for Gut Microbiota Interventions in Cancer Immunotherapy. Clin. Cancer Res. 2022, 28, 4370–4384.
  25. Spencer, C.N.; McQuade, J.L.; Gopalakrishnan, V.; McCulloch, J.A.; Vetizou, M.; Cogdill, A.P.; Khan, M.A.W.; Zhang, X.; White, M.G.; Peterson, C.B.; et al. Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response. Science 2021, 374, 1632–1640.
  26. Cigarran Guldris, S.; González Parra, E.; Cases Amenós, A. Gut microbiota in chronic kidney disease. Nefrologia 2017, 37, 9–19.
  27. Panche, A.N.; Diwan, A.D.; Chandra, S.R. Flavonoids: An overview. J. Nutr. Sci. 2016, 5, e47.
  28. Molan, A.L.; Liu, Z.; Plimmer, G. Evaluation of the effect of blackcurrant products on gut microbiota and on markers of risk for colon cancer in humans. Phytother. Res. 2014, 28, 416–422.
  29. Sun, H.; Zhang, P.; Zhu, Y.; Lou, Q.; He, S. Antioxidant and prebiotic activity of five peonidin-based anthocyanins extracted from purple sweet potato (Ipomoea batatas (L.) Lam.). Sci. Rep. 2018, 8, 5018.
  30. Yu, Q.; Yu, F.; Li, Q.; Zhang, J.; Peng, Y.; Wang, X.; Li, T.; Yin, N.; Sun, G.; Ouyang, H.; et al. Anthocyanin-Rich Butterfly Pea Flower Extract Ameliorating Low-Grade Inflammation in a High-Fat-Diet and Lipopolysaccharide-Induced Mouse Model. J. Agric. Food Chem. 2023, 71, 11941–11956.
  31. Olas, B. Probiotics, Prebiotics and Synbiotics-A Promising Strategy in Prevention and Treatment of Cardiovascular Diseases? Int. J. Mol. Sci. 2020, 21, 9737.
  32. Swanson, K.S.; Gibson, G.R.; Hutkins, R.; Reimer, R.A.; Reid, G.; Verbeke, K.; Scott, K.P.; Holscher, H.D.; Azad, M.B.; Delzenne, N.M.; et al. The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics. Nat. Rev. Gastroenterol. Hepatol. 2020, 17, 687–701.
  33. You, S.; Ma, Y.; Yan, B.; Pei, W.; Wu, Q.; Ding, C.; Huang, C. The promotion mechanism of prebiotics for probiotics: A review. Front. Nutr. 2022, 9, 1000517.
  34. Davison, J.M.; Wischmeyer, P.E. Probiotic and synbiotic therapy in the critically ill: State of the art. Nutrition 2019, 59, 29–36.
  35. Dehghani, M.H.; Saghafi, F.; Bordbari, Z.; Zare-Kamali, J.; Jafari-Nedooshan, J.; Sahebnasagh, A. Investigating the effect of oral synbiotic on enteral feeding tolerance in critically ill patients: A double-blinded controlled clinical trial of gut microbiota. Nutr. Clin. Pract. 2023, 38, 402–410.
  36. Shimizu, K.; Yamada, T.; Ogura, H.; Mohri, T.; Kiguchi, T.; Fujimi, S.; Asahara, T.; Yamada, T.; Ojima, M.; Ikeda, M.; et al. Synbiotics modulate gut microbiota and reduce enteritis and ventilator-associated pneumonia in patients with sepsis: A randomized controlled trial. Crit. Care 2018, 22, 239.
  37. Rohith, G.; Sureshkumar, S.; Anandhi, A.; Kate, V.; Rajesh, B.S.; Abdulbasith, K.M.; Nanda, N.; Palanivel, C.; Vijayakumar, C. Effect of Synbiotics in Reducing the Systemic Inflammatory Response and Septic Complications in Moderately Severe and Severe Acute Pancreatitis: A Prospective Parallel-Arm Double-Blind Randomized Trial. Dig. Dis. Sci. 2023, 68, 969–977.
  38. Shi, Y.; Cui, H.; Wang, F.; Zhang, Y.; Xu, Q.; Liu, D.; Wang, K.; Hou, S. Role of gut microbiota in postoperative complications and prognosis of gastrointestinal surgery: A narrative review. Medicine 2022, 101, e29826.
  39. Sharif, S.; Greer, A.; Skorupski, C.; Hao, Q.; Johnstone, J.; Dionne, J.C.; Lau, V.; Manzanares, W.; Eltorki, M.; Duan, E.; et al. Probiotics in Critical Illness: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Crit. Care Med. 2022, 50, 1175–1186.
  40. Lan, S.H.; Hung, S.H.; Chang, S.P.; Lu, L.C.; Lai, C.C.; Lin, W.T. Pro-, pre- and synbiotics for the prevention of incidental ventilator-associated pneumonia among critically ill patients: A systematic review and meta-analysis of randomized controlled trials. Expert Rev. Anti-Infect. Ther. 2022, 20, 1205–1215.
  41. Haak, B.W.; Prescott, H.C.; Wiersinga, W.J. Therapeutic Potential of the Gut Microbiota in the Prevention and Treatment of Sepsis. Front. Immunol. 2018, 9, 2042.
  42. Suez, J.; Zmora, N.; Zilberman-Schapira, G.; Mor, U.; Dori-Bachash, M.; Bashiardes, S.; Zur, M.; Regev-Lehavi, D.; Ben-Zeev Brik, R.; Federici, S.; et al. Post-Antibiotic Gut Mucosal Microbiome Reconstitution Is Impaired by Probiotics and Improved by Autologous FMT. Cell 2018, 174, 1406–1423.e1416.
  43. Matzaras, R.; Nikopoulou, A.; Protonotariou, E.; Christaki, E. Gut Microbiota Modulation and Prevention of Dysbiosis as an Alternative Approach to Antimicrobial Resistance: A Narrative Review. Yale J. Biol. Med. 2022, 95, 479–494.
  44. Saha, S.; Tariq, R.; Tosh, P.K.; Pardi, D.S.; Khanna, S. Faecal microbiota transplantation for eradicating carriage of multidrug-resistant organisms: A systematic review. Clin. Microbiol. Infect. 2019, 25, 958–963.
  45. Campos-Madueno, E.I.; Moradi, M.; Eddoubaji, Y.; Shahi, F.; Moradi, S.; Bernasconi, O.J.; Moser, A.I.; Endimiani, A. Intestinal colonization with multidrug-resistant Enterobacterales: Screening, epidemiology, clinical impact, and strategies to decolonize carriers. Eur. J. Clin. Microbiol. Infect. Dis. 2023, 42, 229–254.
  46. Ott, S.J.; Waetzig, G.H.; Rehman, A.; Moltzau-Anderson, J.; Bharti, R.; Grasis, J.A.; Cassidy, L.; Tholey, A.; Fickenscher, H.; Seegert, D.; et al. Efficacy of Sterile Fecal Filtrate Transfer for Treating Patients With Clostridium difficile Infection. Gastroenterology 2017, 152, 799–811.e797.
  47. Van Treuren, W.; Dodd, D. Microbial Contribution to the Human Metabolome: Implications for Health and Disease. Annu. Rev. Pathol. Mech. Dis. 2020, 15, 345–369.
  48. Sun, M.; Wu, W.; Liu, Z.; Cong, Y. Microbiota metabolite short chain fatty acids, GPCR, and inflammatory bowel diseases. J. Gastroenterol. 2017, 52, 1–8.
  49. Ho, K.M.; Kalgudi, S.; Corbett, J.M.; Litton, E. Gut microbiota in surgical and critically ill patients. Anaesth. Intensive Care 2020, 48, 179–195.
  50. Blander, J.M.; Longman, R.S.; Iliev, I.D.; Sonnenberg, G.F.; Artis, D. Regulation of inflammation by microbiota interactions with the host. Nat. Immunol. 2017, 18, 851–860.
  51. Keskey, R.; Cone, J.T.; DeFazio, J.R.; Alverdy, J.C. The use of fecal microbiota transplant in sepsis. Transl. Res. 2020, 226, 12–25.
  52. Kim, C.H. Control of lymphocyte functions by gut microbiota-derived short-chain fatty acids. Cell Mol. Immunol. 2021, 18, 1161–1171.
  53. Yin, Y.; Sichler, A.; Ecker, J.; Laschinger, M.; Liebisch, G.; Höring, M.; Basic, M.; Bleich, A.; Zhang, X.J.; Kübelsbeck, L.; et al. Gut microbiota promote liver regeneration through hepatic membrane phospholipid biosynthesis. J. Hepatol. 2023, 78, 820–835.
  54. Hua, Q.; Han, Y.; Zhao, H.; Zhang, H.; Yan, B.; Pei, S.; He, X.; Li, Y.; Meng, X.; Chen, L.; et al. Punicalagin alleviates renal injury via the gut-kidney axis in high-fat diet-induced diabetic mice. Food Funct. 2022, 13, 867–879.
  55. Wang, Z.; Sun, Y.; Han, Y.; Chen, X.; Gong, P.; Zhai, P.; Yao, W.; Ba, Q.; Wang, H. Eucommia bark/leaf extract improves HFD-induced lipid metabolism disorders via targeting gut microbiota to activate the Fiaf-LPL gut-liver axis and SCFAs-GPR43 gut-fat axis. Phytomedicine 2023, 110, 154652.
  56. Zaiss, M.M.; Jones, R.M.; Schett, G.; Pacifici, R. The gut-bone axis: How bacterial metabolites bridge the distance. J. Clin. Investig. 2019, 129, 3018–3028.
  57. Mahmud, M.R.; Akter, S.; Tamanna, S.K.; Mazumder, L.; Esti, I.Z.; Banerjee, S.; Akter, S.; Hasan, M.R.; Acharjee, M.; Hossain, M.S.; et al. Impact of gut microbiome on skin health: Gut-skin axis observed through the lenses of therapeutics and skin diseases. Gut Microbes 2022, 14, 2096995.
  58. Matsiras, D.; Bezati, S.; Ventoulis, I.; Verras, C.; Parissis, J.; Polyzogopoulou, E. Gut Failure: A Review of the Pathophysiology and Therapeutic Potentials in the Gut-Heart Axis. J. Clin. Med. 2023, 12, 2567.
  59. Zhang, F.; Wan, Y.; Zuo, T.; Yeoh, Y.K.; Liu, Q.; Zhang, L.; Zhan, H.; Lu, W.; Xu, W.; Lui, G.C.Y.; et al. Prolonged Impairment of Short-Chain Fatty Acid and L-Isoleucine Biosynthesis in Gut Microbiome in Patients With COVID-19. Gastroenterology 2022, 162, 548–561.e544.
  60. Hao, F.; Tian, M.; Zhang, X.; Jin, X.; Jiang, Y.; Sun, X.; Wang, Y.; Peng, P.; Liu, J.; Xia, C.; et al. Butyrate enhances CPT1A activity to promote fatty acid oxidation and iTreg differentiation. Proc. Natl. Acad. Sci. USA 2021, 118, e2014681118.
  61. Zhang, H.; Xu, J.; Wu, Q.; Fang, H.; Shao, X.; Ouyang, X.; He, Z.; Deng, Y.; Chen, C. Gut Microbiota Mediates the Susceptibility of Mice to Sepsis-Associated Encephalopathy by Butyric Acid. J. Inflamm. Res. 2022, 15, 2103–2119.
  62. Zhou, D.; Pan, Q.; Xin, F.Z.; Zhang, R.N.; He, C.X.; Chen, G.Y.; Liu, C.; Chen, Y.W.; Fan, J.G. Sodium butyrate attenuates high-fat diet-induced steatohepatitis in mice by improving gut microbiota and gastrointestinal barrier. World J. Gastroenterol. 2017, 23, 60–75.
  63. Bach Knudsen, K.E.; Lærke, H.N.; Hedemann, M.S.; Nielsen, T.S.; Ingerslev, A.K.; Gundelund Nielsen, D.S.; Theil, P.K.; Purup, S.; Hald, S.; Schioldan, A.G.; et al. Impact of Diet-Modulated Butyrate Production on Intestinal Barrier Function and Inflammation. Nutrients 2018, 10, 1499.
  64. Kim, S.M.; DeFazio, J.R.; Hyoju, S.K.; Sangani, K.; Keskey, R.; Krezalek, M.A.; Khodarev, N.N.; Sangwan, N.; Christley, S.; Harris, K.G.; et al. Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity. Nat. Commun. 2020, 11, 2354.
  65. Tian, L.; Zhou, X.Q.; Jiang, W.D.; Liu, Y.; Wu, P.; Jiang, J.; Kuang, S.Y.; Tang, L.; Tang, W.N.; Zhang, Y.A.; et al. Sodium butyrate improved intestinal immune function associated with NF-κB and p38MAPK signalling pathways in young grass carp (Ctenopharyngodon idella). Fish Shellfish. Immunol. 2017, 66, 548–563.
  66. Li, X.Y.; He, C.; Zhu, Y.; Lu, N.H. Role of gut microbiota on intestinal barrier function in acute pancreatitis. World J. Gastroenterol. 2020, 26, 2187–2193.
  67. Zhao, Y.; Chen, F.; Wu, W.; Sun, M.; Bilotta, A.J.; Yao, S.; Xiao, Y.; Huang, X.; Eaves-Pyles, T.D.; Golovko, G.; et al. GPR43 mediates microbiota metabolite SCFA regulation of antimicrobial peptide expression in intestinal epithelial cells via activation of mTOR and STAT3. Mucosal Immunol. 2018, 11, 752–762.
  68. Tomova, A.; Bukovsky, I.; Rembert, E.; Yonas, W.; Alwarith, J.; Barnard, N.D.; Kahleova, H. The Effects of Vegetarian and Vegan Diets on Gut Microbiota. Front. Nutr. 2019, 6, 47.
  69. Schulthess, J.; Pandey, S.; Capitani, M.; Rue-Albrecht, K.C.; Arnold, I.; Franchini, F.; Chomka, A.; Ilott, N.E.; Johnston, D.G.W.; Pires, E.; et al. The Short Chain Fatty Acid Butyrate Imprints an Antimicrobial Program in Macrophages. Immunity 2019, 50, 432–445.e437.
  70. Chang, P.V.; Hao, L.; Offermanns, S.; Medzhitov, R. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc. Natl. Acad. Sci. USA 2014, 111, 2247–2252.
  71. 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.
  72. Fellows, R.; Denizot, J.; Stellato, C.; Cuomo, A.; Jain, P.; Stoyanova, E.; Balázsi, S.; Hajnády, Z.; Liebert, A.; Kazakevych, J.; et al. Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases. Nat. Commun. 2018, 9, 105.
  73. Smith, P.M.; Howitt, M.R.; Panikov, N.; Michaud, M.; Gallini, C.A.; Bohlooly, Y.M.; Glickman, J.N.; Garrett, W.S. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 2013, 341, 569–573.
  74. Arpaia, N.; Campbell, C.; Fan, X.; Dikiy, S.; van der Veeken, J.; deRoos, P.; Liu, H.; Cross, J.R.; Pfeffer, K.; Coffer, P.J.; et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 2013, 504, 451–455.
  75. Melhem, H.; Kaya, B.; Ayata, C.K.; Hruz, P.; Niess, J.H. Metabolite-Sensing G Protein-Coupled Receptors Connect the Diet-Microbiota-Metabolites Axis to Inflammatory Bowel Disease. Cells 2019, 8, 450.
  76. Li, N.; Liu, X.X.; Hong, M.; Huang, X.Z.; Chen, H.; Xu, J.H.; Wang, C.; Zhang, Y.X.; Zhong, J.X.; Nie, H.; et al. Sodium butyrate alleviates LPS-induced acute lung injury in mice via inhibiting HMGB1 release. Int. Immunopharmacol. 2018, 56, 242–248.
  77. Liu, J.; Chang, G.; Huang, J.; Wang, Y.; Ma, N.; Roy, A.C.; Shen, X. Sodium Butyrate Inhibits the Inflammation of Lipopolysaccharide-Induced Acute Lung Injury in Mice by Regulating the Toll-Like Receptor 4/Nuclear Factor κB Signaling Pathway. J. Agric. Food Chem. 2019, 67, 1674–1682.
  78. Dang, A.T.; Marsland, B.J. Microbes, metabolites, and the gut-lung axis. Mucosal Immunol. 2019, 12, 843–850.
  79. Yang, W.; Yu, T.; Huang, X.; Bilotta, A.J.; Xu, L.; Lu, Y.; Sun, J.; Pan, F.; Zhou, J.; Zhang, W.; et al. Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL-22 production and gut immunity. Nat. Commun. 2020, 11, 4457.
  80. Trompette, A.; Gollwitzer, E.S.; Yadava, K.; Sichelstiel, A.K.; Sprenger, N.; Ngom-Bru, C.; Blanchard, C.; Junt, T.; Nicod, L.P.; Harris, N.L.; et al. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat. Med. 2014, 20, 159–166.
  81. Li, Y.J.; Chen, X.; Kwan, T.K.; Loh, Y.W.; Singer, J.; Liu, Y.; Ma, J.; Tan, J.; Macia, L.; Mackay, C.R.; et al. Dietary Fiber Protects against Diabetic Nephropathy through Short-Chain Fatty Acid-Mediated Activation of G Protein-Coupled Receptors GPR43 and GPR109A. J. Am. Soc. Nephrol. 2020, 31, 1267–1281.
  82. Vinolo, M.A.; Rodrigues, H.G.; Hatanaka, E.; Hebeda, C.B.; Farsky, S.H.; Curi, R. Short-chain fatty acids stimulate the migration of neutrophils to inflammatory sites. Clin. Sci. 2009, 117, 331–338.
  83. Vinolo, M.A.; Hatanaka, E.; Lambertucci, R.H.; Newsholme, P.; Curi, R. Effects of short chain fatty acids on effector mechanisms of neutrophils. Cell Biochem. Funct. 2009, 27, 48–55.
  84. Ikeda, T.; Nishida, A.; Yamano, M.; Kimura, I. Short-chain fatty acid receptors and gut microbiota as therapeutic targets in metabolic, immune, and neurological diseases. Pharmacol. Ther. 2022, 239, 108273.
  85. Tan, J.; McKenzie, C.; Vuillermin, P.J.; Goverse, G.; Vinuesa, C.G.; Mebius, R.E.; Macia, L.; Mackay, C.R. Dietary Fiber and Bacterial SCFA Enhance Oral Tolerance and Protect against Food Allergy through Diverse Cellular Pathways. Cell Rep. 2016, 15, 2809–2824.
  86. Moonwiriyakit, A.; Wattanaphichet, P.; Chatsudthipong, V.; Muanprasat, C. GPR40 receptor activation promotes tight junction assembly in airway epithelial cells via AMPK-dependent mechanisms. Tissue Barriers 2018, 6, 1–12.
  87. Kimura, I.; Ichimura, A.; Ohue-Kitano, R.; Igarashi, M. Free Fatty Acid Receptors in Health and Disease. Physiol. Rev. 2020, 100, 171–210.
  88. Wu, Y.; He, F.; Zhang, C.; Zhang, Q.; Su, X.; Zhu, X.; Liu, A.; Shi, W.; Lin, W.; Jin, Z.; et al. Melatonin alleviates titanium nanoparticles induced osteolysis via activation of butyrate/GPR109A signaling pathway. J. Nanobiotechnology 2021, 19, 170.
  89. Weng, J.; Wu, H.; Xu, Z.; Xi, H.; Chen, C.; Chen, D.; Gong, Y.; Hua, Y.; Wang, Z. The role of propionic acid at diagnosis predicts mortality in patients with septic shock. J. Crit. Care 2018, 43, 95–101.
  90. Koh, A.; De Vadder, F.; Kovatcheva-Datchary, P.; Bäckhed, F. From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites. Cell 2016, 165, 1332–1345.
  91. Xu, M.; Wang, C.; Li, N.; Wang, J.; Zhang, Y.; Deng, X. Intraperitoneal Injection of Acetate Protects Mice Against Lipopolysaccharide (LPS)-Induced Acute Lung Injury Through Its Anti-Inflammatory and Anti-Oxidative Ability. Med. Sci. Monit. 2019, 25, 2278–2288.
  92. Ji, J.J.; Sun, Q.M.; Nie, D.Y.; Wang, Q.; Zhang, H.; Qin, F.F.; Wang, Q.S.; Lu, S.F.; Pang, G.M.; Lu, Z.G. Probiotics protect against RSV infection by modulating the microbiota-alveolar-macrophage axis. Acta Pharmacol. Sin. 2021, 42, 1630–1641.
  93. Wang, M.; Zhao, H.; Wen, X.; Ho, C.T.; Li, S. Citrus flavonoids and the intestinal barrier: Interactions and effects. Compr. Rev. Food Sci. Food Saf. 2021, 20, 225–251.
  94. Joardder, M.U.H.; Kumar, C.; Karim, M.A. Prediction of porosity of food materials during drying: Current challenges and directions. Crit. Rev. Food Sci. Nutr. 2018, 58, 2896–2907.
  95. Chen, T.; Yang, C.S. Biological fates of tea polyphenols and their interactions with microbiota in the gastrointestinal tract: Implications on health effects. Crit. Rev. Food Sci. Nutr. 2020, 60, 2691–2709.
  96. Lambert, M.A.; Moss, C.W. Production of p-hydroxyhydrocinnamic acid from tyrosine by Peptostreptococcus anaerobius. J. Clin. Microbiol. 1980, 12, 291–293.
  97. Oteiza, P.I.; Fraga, C.G.; Mills, D.A.; Taft, D.H. Flavonoids and the gastrointestinal tract: Local and systemic effects. Mol. Asp. Med. 2018, 61, 41–49.
  98. Wei, Y.; Gao, J.; Kou, Y.; Liu, M.; Meng, L.; Zheng, X.; Xu, S.; Liang, M.; Sun, H.; Liu, Z.; et al. The intestinal microbial metabolite desaminotyrosine is an anti-inflammatory molecule that modulates local and systemic immune homeostasis. FASEB J. 2020, 34, 16117–16128.
  99. Hu, L.; Wu, C.; Zhang, Z.; Liu, M.; Maruthi Prasad, E.; Chen, Y.; Wang, K. Pinocembrin Protects Against Dextran Sulfate Sodium-Induced Rats Colitis by Ameliorating Inflammation, Improving Barrier Function and Modulating Gut Microbiota. Front. Physiol. 2019, 10, 908.
  100. Yi, Y.S. Regulatory Roles of Flavonoids on Inflammasome Activation during Inflammatory Responses. Mol. Nutr. Food Res. 2018, 62, e1800147.
  101. Liskova, A.; Samec, M.; Koklesova, L.; Samuel, S.M.; Zhai, K.; Al-Ishaq, R.K.; Abotaleb, M.; Nosal, V.; Kajo, K.; Ashrafizadeh, M.; et al. Flavonoids against the SARS-CoV-2 induced inflammatory storm. Biomed. Pharmacother. 2021, 138, 111430.
  102. Steed, A.L.; Christophi, G.P.; Kaiko, G.E.; Sun, L.; Goodwin, V.M.; Jain, U.; Esaulova, E.; Artyomov, M.N.; Morales, D.J.; Holtzman, M.J.; et al. The microbial metabolite desaminotyrosine protects from influenza through type I interferon. Science 2017, 357, 498–502.
  103. Somerville, V.S.; Braakhuis, A.J.; Hopkins, W.G. Effect of Flavonoids on Upper Respiratory Tract Infections and Immune Function: A Systematic Review and Meta-Analysis. Adv. Nutr. 2016, 7, 488–497.
  104. Li, J.; Zhang, L.; Wu, T.; Li, Y.; Zhou, X.; Ruan, Z. Indole-3-propionic Acid Improved the Intestinal Barrier by Enhancing Epithelial Barrier and Mucus Barrier. J. Agric. Food Chem. 2021, 69, 1487–1495.
  105. Fang, H.; Fang, M.; Wang, Y.; Zhang, H.; Li, J.; Chen, J.; Wu, Q.; He, L.; Xu, J.; Deng, J.; et al. Indole-3-Propionic Acid as a Potential Therapeutic Agent for Sepsis-Induced Gut Microbiota Disturbance. Microbiol. Spectr. 2022, 10, e0012522.
  106. Beloborodova, N.V.; Olenin, A.Y.; Pautova, A.K. Metabolomic findings in sepsis as a damage of host-microbial metabolism integration. J. Crit. Care 2018, 43, 246–255.
  107. Chernevskaya, E.; Beloborodova, N.; Klimenko, N.; Pautova, A.; Shilkin, D.; Gusarov, V.; Tyakht, A. Serum and fecal profiles of aromatic microbial metabolites reflect gut microbiota disruption in critically ill patients: A prospective observational pilot study. Crit. Care 2020, 24, 312.
  108. Tang, W.H.; 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.
  109. Szychowiak, P.; Villageois-Tran, K.; Patrier, J.; Timsit, J.F.; Ruppé, É. The role of the microbiota in the management of intensive care patients. Ann. Intensive Care 2022, 12, 3.
  110. Corriero, A.; Gadaleta, R.M.; Puntillo, F.; Inchingolo, F.; Moschetta, A.; Brienza, N. The central role of the gut in intensive care. Crit. Care 2022, 26, 379.
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.
This entry is offline, you can click here to edit this entry!
ScholarVision Creations
Feedback