О роли ароматических микробных метаболитов
Ключевые слова:
критические состояния, метаболомика, фенилкарбоновые кислоты, органная дисфункция, сепсис
Аннотация
Интеграция метаболизма макроорганизма и его микробиоты, обеспечивающая в норме симбиоз и саногенез, нарушается при заболеваниях, травме, критическом состоянии, и вектор взаимодействия может изменяться в пользу прокариотов по принципу «метаболиты бактерий – против хозяина». Анализ литературы показал, что, с одной стороны, имеется живой интерес к ароматическим микробным метаболитам, с другой – отсутствует четкое представление об их роли в организме человека. Публикации о ФКК, как правило, не связаны между собой по тематике, и направлены на решение тех или иных прикладных задач в разных областях биологии и медицины. Цель обзора – анализ информации о происхождении, биологических эффектах ФКК в экспериментах in vitro и in vivo, и клинических наблюдениях. Обобщая результаты приведенных в обзоре исследований на клеточном, субклеточном и молекулярном уровнях, логично предположить участие ароматических микробных метаболитов в патогенезе полиорганной недостаточности при сепсисе. Наиболее перспективным для раскрытия роли ароматических микробных метаболитов представляется изучение механизмов вторичной почечной недостаточности и септической энцефалопатии. Важным направлением для будущих исследований является изучение влияния продуктов микробной биодеградации ароматических соединений на развитие диссеминированного внутрисосудистого свертывания крови, артериальной гипотензии и септического шока. Результаты дальнейших исследований будут иметь не только фундаментальное значение, но и обогатят практическую медицину новыми диагностическими и лечебными технологиями.
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Литература
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2. Beloborodova N.V., Moroz V.V., Osipov A.A., Bedova A.Yu., Olenin A.Yu., Getsina M.L. et al. Normal level of sepsis-associated phenylcarboxylic acids in human serum. Biochemistry (Moscow). 2015; 80(3) 374-378.
3. Белобородова Н.В. Интеграция метаболизма человека и его микробиома при критических состояниях. Общая реаниматология. 2012; 8(4): 42–54.
4. Белобородова Н.В. Сепсис – новый взгляд на проблему. Терапевт. архив. 2013; 11: 82-90.
5. Beloborodova N., Moroz V., Osipov A., Bedova A., Sarshor Y., Pautova A. et al. Disbalance of microbial metabolites of aromatic acids affects the severity in critically ill patients. Critical Care. 2016; 20(Suppl 2):P026
6. Herrmann K.M. The Shikimate Pathway: Early Steps in the Biosynthesis of Aromatic Compounds. Plant Cell. 1995; 7(7): 907–919.
7. Srinivasan P.R., Katagiri M., Sprinson D.B. The conversion of phosphoenolpyruvic acid and D-erythrose-4-phosphate to 5-de-hydroquinic acid. J. Biol. Chem. 1959; 234(4): 713-5.
8. Russell W.R., Duncan S.H., Scobbie L., Duncan G., Cantlay L., Calder A.G. Major phenylpropanoid-derived metabolites in the human gut can arise from microbial fermentation of protein. Mol. Nutr. Food Res. 2013; 57(3): 523-35.
9. Valerio F., Lavermicocca P., Pascale M., Visconti A. Production of phenyllactic acid by lactic acid bacteria: an approach to the selection of strains contributing to food quality and preservation. FEMS Microbiology Letters. 2004; 233(2): 289-95.
10. Gao K., Xu A., Krul C., Venema K., Liu Y., Niu Y. et al. Of the major phenolic acids formed during human microbial fermentation of tea, citrus, and soy flavonoid supplements, only 3,4-dihydroxyphenylacetic acid has antiproliferative activity. J Nutr. 2006; 136(1): 52-7.
11. González-Barrio R., Edwards C.A., Crozier A. Colonic Catabolism of Ellagitannins, Ellagic Acid, and Raspberry Anthocyanins: In Vivo and In Vitro Studies. Drug Metab. Dispos. 2011; 39(9): 1680-8.
12. Lee H.C., Jenner A.M., Low C.S., Lee Y.K. Effect of tea phenolics and their aromatic fecal bacterial metabolites on intestinal microbiota. Research in Microbiology. 2006; 157(9): 876-84.
13. Jenner A.M., Rafter J., Halliwell B. Human fecal water content of phenolics: The extent of colonic exposure to phenolic compounds. Free Radic. Biol. Med. 2005; 38(6): 763-72.
14. Beloborodova N.V., Khodakova A.S., Bairamov I.T., Olenin A.Y. Microbial origin of phenylcarboxylic acids in the human body. Biochemistry (Moscow). 2009. 74(12): 1350-1355.
15. Clemens P.C., Schunemann M.H., Hoffman G.F., Kohlschutter A. Plasma concentrations of phenyllactic acid in phenylketonuria. J. Inherit. Metab. Dis. 1990; 13(2): 227-8.
16. Chalmersa R.A., Wattsa R.W.E. Quantitative studies on the urinary excretion of unconjugated aromatic acids in phenylketonuria. Clin. Chim. Acta. 1974; 55(3): 281-94.
17. Crawhall J.C., Mamer O., Tjoa S., Claveau J.C. Urinary phenolic acids in tyrosinemia. identification and quantitation by gas chromatography-mass spectrometry. Clin. Chim. Acta. 1971; 34(1): 47-54.
18. Nakamura K., Tanaka Y., Mitsubuchi H., Endo F. Animal models of tirosinemia. J. Nutr. 2007; 137(6 Suppl 1): 1556S-1560S.
19. Rogers A.J., McGeachie M., Baron R.M., Gazourian L., Haspel J.A., Nakahira K. et al. Metabolomic derangements are associated with mortality in critically ill adult patients. PLoS One. 2014; 9(1): e87538.
20. Scholze A., Jankowski V., Henning L., Haass W., Wittstock A., Suvd-Erdene S. et al. Phenylacetic acid and arterial vascular properties in patients with chronic kidney disease stage 5 on hemodialysis therapy. Nephron Clin. Pract. 2007; 107(1): c1-6.
21. Ситкин С.И., Ткаченко Е.И., Вахитов Т.Я., Орешко Л.С., Жигалова Т.Н. Особенности метаболома сыворотки крови при язвенном колите и целиакии по данным газовой хроматографии – масс-спектрометрии. Гастроэнтерология Санкт-Петербурга. 2013; 3–4: 2-10.
22. Cohen G., Raupachova J., Hörl W.H. The uraemic toxin phenylacetic acid contributes to inflammation by priming polymorphonuclear leucocytes. Nephrol. Dial. Transplant. 2013; 28(2): 421-9.
23. Fong M.Y., McDunn J., Kakar S.S. Identification of metabolites in the normal ovary and their transformation in primary and metastatic ovarian cancer. PLoS One. 2011; 6(5): e19963.
24. Белобородова Н.В., Оленин А.Ю., Ходакова А.С., Черневская Е.А., Хабиб О.Н. Происхождение и клиническое значение низкомолекулярных фенольных метаболитов в сыворотке крови человека. Анестезиология и реаниматология. 2012; 5: 37-41.
25. Kobayashi K., Imazu Y., Shohmori T. p-Hydroxyphenylacetic Acid Concentration in the CSF of Patients with Neurological and Psychiatric Disorders. In: Neurobiology of the Trace Amines (eds Boulton A. A. et al.) 543–548 (Humana Press, 1984).
26. Sandler M., Ruthven C.R., Goodwin B.L., Coppen A. Decreased cerebrospinal fluid concentration of free phenylacetic acid in depressive illness. Clin. Chim. Acta. 1979; 93(1): 169-71.
27. Gill C.I., McDougall G.J., Glidewell S., Stewart D., Shen Q., Tuohy K. et al. Profiling of Phenols in Human Fecal Water after Raspberry Supplementation. J. Agric. Food Chem. 2010; 58(19): 10389-95.
28. Khodakova A., Beloborodova N. Khodakova, A. Microbial metabolites in the blood of patients with sepsis. Crit. Care. 2007; 11(Suppl 4): P5.
29. Beloborodova N., Moroz V., Bedova A., Sarshor Y., Osipov A., Chernevskaya K. High levels of phenylcarboxylic acids reflect the severity in ICU patients and affect phagocytic activity of neutrophils. Critical Care 2016, 20(Suppl 1): P3. DOI 10.1186/s13054-016-1204-x
30. Gusovsky F., Sabelli H., Fawcett J., Edwards J., Javaid J.I. Gas-liquid chromatographic determination of total phenylacetic acid in urine. Anal. Biochem. 1984; 136(1): 202-7.
31. Henning S.M., Wang P., Abgaryan N., Vicinanza R., Oliveira D.M., Zhang Y. et al. Phenolic acid concentrations in plasma and urine from men consuming green or black tea and potential chemopreventive properties for colon cancer. Mol. Nutr. Food Res. 2013; 57(3): 483–493.
32. Nardini M., Natella F., Scaccini C., Ghiselli A. Phenolic acids from beer are absorbed and extensively metabolized in humans. J Nutr Biochem. 2006; 17(1): 14-22.
33. Aronov P.A., Luo F.J., Plummer N.S., Quan Z., Holmes S., Hostetter T.H. et al. Colonic contribution to uremic solutes. J. Am. Soc. Nephrol. 2011; 22(9): 1769-76.
34. Haan E., Brown G., Bankier A., Mitchell D., Hunt S., Blakey J. et al. Severe illness caused by the products of bacterial metabolism in a child with a short gut. Eur. J. Pediatr. 1985; 144(1): 63-5.
35. Muting D., Wuzel H., Bucsis L., Flasshoff H.J. Urinary p-hydroxyphenyllactic acid as indicator of hepatic encephalopathy in patients with hepatic cirrhosis. Lancet. 1985; 2(8468): 1365-6.
36. Leibich H.M., Pickert A. Gas chromatographic profiling of phenolic acids in urine of patients with cirrhosis of the liver. Journal of Chromatography. 1985; 338(1): 25-32.
37. Jones M.R., Kopple J.D., Swendseid M.E. Phenylalanine metabolism in uremic and normal man. Kidney Int. 1978; 14(2): 169-79.
38. Niwa T., Ohki T., Maeda K., Saito A., Ohta K., Kobayashi K. A gas chromatographic-mass spectrometric assay for nine hydroxyphenolic acids in uremic serum. Clin. Chim. Acta. 1979; 96(3): 247-54.
39. Хорошилов С.Е., Белобородова Н.В., Никулин А.В., Бедова А.Ю. Влияние экстракорпоральной детоксикации на уровень ароматических микробных метаболитов в сыворотке крови при сепсисе. Общая реаниматология. 2015; 11(5): 6–14.
40. Bunchman T.E., Barletta G.M., Winters J.W., Gardner J.J., Crumb T.L., McBryde K.D. Phenylacetate and benzoate clearance in a hyperammonemic infant on sequential hemodialysis and hemofiltration. Pediatr. Nephrol. 2007; 22(7): 1062-5.
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64. Beloborodova N.V., Moroz V.V., Osipov A.A., Vlasenko A.V., Fateev K.M., Sarshor Y.N. et al. Prognostic value phenylcarboxylic acids in patients with acute abdomen. Shock. 2015; 44 (Suppl. 2) 13.
2. Beloborodova N.V., Moroz V.V., Osipov A.A., Bedova A.Yu., Olenin A.Yu., Getsina M.L. et al. Normal level of sepsis-associated phenylcarboxylic acids in human serum. Biochemistry (Moscow). 2015; 80(3) 374-378.
3. Белобородова Н.В. Интеграция метаболизма человека и его микробиома при критических состояниях. Общая реаниматология. 2012; 8(4): 42–54.
4. Белобородова Н.В. Сепсис – новый взгляд на проблему. Терапевт. архив. 2013; 11: 82-90.
5. Beloborodova N., Moroz V., Osipov A., Bedova A., Sarshor Y., Pautova A. et al. Disbalance of microbial metabolites of aromatic acids affects the severity in critically ill patients. Critical Care. 2016; 20(Suppl 2):P026
6. Herrmann K.M. The Shikimate Pathway: Early Steps in the Biosynthesis of Aromatic Compounds. Plant Cell. 1995; 7(7): 907–919.
7. Srinivasan P.R., Katagiri M., Sprinson D.B. The conversion of phosphoenolpyruvic acid and D-erythrose-4-phosphate to 5-de-hydroquinic acid. J. Biol. Chem. 1959; 234(4): 713-5.
8. Russell W.R., Duncan S.H., Scobbie L., Duncan G., Cantlay L., Calder A.G. Major phenylpropanoid-derived metabolites in the human gut can arise from microbial fermentation of protein. Mol. Nutr. Food Res. 2013; 57(3): 523-35.
9. Valerio F., Lavermicocca P., Pascale M., Visconti A. Production of phenyllactic acid by lactic acid bacteria: an approach to the selection of strains contributing to food quality and preservation. FEMS Microbiology Letters. 2004; 233(2): 289-95.
10. Gao K., Xu A., Krul C., Venema K., Liu Y., Niu Y. et al. Of the major phenolic acids formed during human microbial fermentation of tea, citrus, and soy flavonoid supplements, only 3,4-dihydroxyphenylacetic acid has antiproliferative activity. J Nutr. 2006; 136(1): 52-7.
11. González-Barrio R., Edwards C.A., Crozier A. Colonic Catabolism of Ellagitannins, Ellagic Acid, and Raspberry Anthocyanins: In Vivo and In Vitro Studies. Drug Metab. Dispos. 2011; 39(9): 1680-8.
12. Lee H.C., Jenner A.M., Low C.S., Lee Y.K. Effect of tea phenolics and their aromatic fecal bacterial metabolites on intestinal microbiota. Research in Microbiology. 2006; 157(9): 876-84.
13. Jenner A.M., Rafter J., Halliwell B. Human fecal water content of phenolics: The extent of colonic exposure to phenolic compounds. Free Radic. Biol. Med. 2005; 38(6): 763-72.
14. Beloborodova N.V., Khodakova A.S., Bairamov I.T., Olenin A.Y. Microbial origin of phenylcarboxylic acids in the human body. Biochemistry (Moscow). 2009. 74(12): 1350-1355.
15. Clemens P.C., Schunemann M.H., Hoffman G.F., Kohlschutter A. Plasma concentrations of phenyllactic acid in phenylketonuria. J. Inherit. Metab. Dis. 1990; 13(2): 227-8.
16. Chalmersa R.A., Wattsa R.W.E. Quantitative studies on the urinary excretion of unconjugated aromatic acids in phenylketonuria. Clin. Chim. Acta. 1974; 55(3): 281-94.
17. Crawhall J.C., Mamer O., Tjoa S., Claveau J.C. Urinary phenolic acids in tyrosinemia. identification and quantitation by gas chromatography-mass spectrometry. Clin. Chim. Acta. 1971; 34(1): 47-54.
18. Nakamura K., Tanaka Y., Mitsubuchi H., Endo F. Animal models of tirosinemia. J. Nutr. 2007; 137(6 Suppl 1): 1556S-1560S.
19. Rogers A.J., McGeachie M., Baron R.M., Gazourian L., Haspel J.A., Nakahira K. et al. Metabolomic derangements are associated with mortality in critically ill adult patients. PLoS One. 2014; 9(1): e87538.
20. Scholze A., Jankowski V., Henning L., Haass W., Wittstock A., Suvd-Erdene S. et al. Phenylacetic acid and arterial vascular properties in patients with chronic kidney disease stage 5 on hemodialysis therapy. Nephron Clin. Pract. 2007; 107(1): c1-6.
21. Ситкин С.И., Ткаченко Е.И., Вахитов Т.Я., Орешко Л.С., Жигалова Т.Н. Особенности метаболома сыворотки крови при язвенном колите и целиакии по данным газовой хроматографии – масс-спектрометрии. Гастроэнтерология Санкт-Петербурга. 2013; 3–4: 2-10.
22. Cohen G., Raupachova J., Hörl W.H. The uraemic toxin phenylacetic acid contributes to inflammation by priming polymorphonuclear leucocytes. Nephrol. Dial. Transplant. 2013; 28(2): 421-9.
23. Fong M.Y., McDunn J., Kakar S.S. Identification of metabolites in the normal ovary and their transformation in primary and metastatic ovarian cancer. PLoS One. 2011; 6(5): e19963.
24. Белобородова Н.В., Оленин А.Ю., Ходакова А.С., Черневская Е.А., Хабиб О.Н. Происхождение и клиническое значение низкомолекулярных фенольных метаболитов в сыворотке крови человека. Анестезиология и реаниматология. 2012; 5: 37-41.
25. Kobayashi K., Imazu Y., Shohmori T. p-Hydroxyphenylacetic Acid Concentration in the CSF of Patients with Neurological and Psychiatric Disorders. In: Neurobiology of the Trace Amines (eds Boulton A. A. et al.) 543–548 (Humana Press, 1984).
26. Sandler M., Ruthven C.R., Goodwin B.L., Coppen A. Decreased cerebrospinal fluid concentration of free phenylacetic acid in depressive illness. Clin. Chim. Acta. 1979; 93(1): 169-71.
27. Gill C.I., McDougall G.J., Glidewell S., Stewart D., Shen Q., Tuohy K. et al. Profiling of Phenols in Human Fecal Water after Raspberry Supplementation. J. Agric. Food Chem. 2010; 58(19): 10389-95.
28. Khodakova A., Beloborodova N. Khodakova, A. Microbial metabolites in the blood of patients with sepsis. Crit. Care. 2007; 11(Suppl 4): P5.
29. Beloborodova N., Moroz V., Bedova A., Sarshor Y., Osipov A., Chernevskaya K. High levels of phenylcarboxylic acids reflect the severity in ICU patients and affect phagocytic activity of neutrophils. Critical Care 2016, 20(Suppl 1): P3. DOI 10.1186/s13054-016-1204-x
30. Gusovsky F., Sabelli H., Fawcett J., Edwards J., Javaid J.I. Gas-liquid chromatographic determination of total phenylacetic acid in urine. Anal. Biochem. 1984; 136(1): 202-7.
31. Henning S.M., Wang P., Abgaryan N., Vicinanza R., Oliveira D.M., Zhang Y. et al. Phenolic acid concentrations in plasma and urine from men consuming green or black tea and potential chemopreventive properties for colon cancer. Mol. Nutr. Food Res. 2013; 57(3): 483–493.
32. Nardini M., Natella F., Scaccini C., Ghiselli A. Phenolic acids from beer are absorbed and extensively metabolized in humans. J Nutr Biochem. 2006; 17(1): 14-22.
33. Aronov P.A., Luo F.J., Plummer N.S., Quan Z., Holmes S., Hostetter T.H. et al. Colonic contribution to uremic solutes. J. Am. Soc. Nephrol. 2011; 22(9): 1769-76.
34. Haan E., Brown G., Bankier A., Mitchell D., Hunt S., Blakey J. et al. Severe illness caused by the products of bacterial metabolism in a child with a short gut. Eur. J. Pediatr. 1985; 144(1): 63-5.
35. Muting D., Wuzel H., Bucsis L., Flasshoff H.J. Urinary p-hydroxyphenyllactic acid as indicator of hepatic encephalopathy in patients with hepatic cirrhosis. Lancet. 1985; 2(8468): 1365-6.
36. Leibich H.M., Pickert A. Gas chromatographic profiling of phenolic acids in urine of patients with cirrhosis of the liver. Journal of Chromatography. 1985; 338(1): 25-32.
37. Jones M.R., Kopple J.D., Swendseid M.E. Phenylalanine metabolism in uremic and normal man. Kidney Int. 1978; 14(2): 169-79.
38. Niwa T., Ohki T., Maeda K., Saito A., Ohta K., Kobayashi K. A gas chromatographic-mass spectrometric assay for nine hydroxyphenolic acids in uremic serum. Clin. Chim. Acta. 1979; 96(3): 247-54.
39. Хорошилов С.Е., Белобородова Н.В., Никулин А.В., Бедова А.Ю. Влияние экстракорпоральной детоксикации на уровень ароматических микробных метаболитов в сыворотке крови при сепсисе. Общая реаниматология. 2015; 11(5): 6–14.
40. Bunchman T.E., Barletta G.M., Winters J.W., Gardner J.J., Crumb T.L., McBryde K.D. Phenylacetate and benzoate clearance in a hyperammonemic infant on sequential hemodialysis and hemofiltration. Pediatr. Nephrol. 2007; 22(7): 1062-5.
41. Shih V.E. Alternative-pathway therapy for hyperammonemia. N. Engl. J. Med. 2007; 356(22): 2321-2.
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Опубликован
2018-01-27
Как цитировать
Белобородова Н. В., Мороз В. В., Бедова А. Ю. О роли ароматических микробных метаболитов // Патологическая физиология и экспериментальная терапия. 2018. Т. 62. № 1. С. 97–108.
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