Propiyonik ve Metilmalonik Asidemide Bağırsak Mikrobiyotasının Etkisi

Öz

Propionik ve metilmalonik asidemi (PA/MMA), propionil CoA ve/veya metilmalonil CoA birikimi ile karakterize, ciddi metabolik krizlere ve klinik komplikasyonlara neden olan kalıtsal metabolik hastalıklardır. Toplam propionat üretiminin önemli bir kısımı bağırsak mikrobiyotasında olmaktadır ve bu durum da bağırsak mikrobiyotasını modifiye edilebilir bir hedef olarak belirlenmiştir. Propionat üretimini azaltmak için oral antibiyotiklerin kullanımı yaygın bir yaklaşımdır ancak uzun dönem antibiyotik kullanımı hastalarda antibiyotiğe karşı direnç gösteren suşların oluşumuna, normal bağırsak mikrobiyotasının bozulmasına ve santral sinir sistemi toksititesine sebep olabileceği de unutulmamalıdır. Kabızlık, bu hasta popülasyonunda kronik bir sorundur ve propionat üretimini etkileyebilir. Propionat yükünü azaltan ve bu klinik sorunları ele alan daha yeni ve etkili hastalık yönetim tekniklerine ihtiyaç vardır. Bu derleme, PA/MMA'da bağırsakla ilgili faktörlerin potansiyel katkısını özetlemekte ve bir yönetim yaklaşımı olarak bağırsak mikrobiyotasını modifiye etmeyi ele almaktadır.

Anahtar Kelimeler

• Propiyonik asidemi
• Metilmalonik asidemi
• Mikrobiyota

Effect of Gut Microbiota on Propionic and Methylmalonic Acidemia

Öz

Propionic and methylmalonic acidemias (PA/MMA) are inherited metabolic disorders characterized by the accumulation of propionyl CoA and/or methylmalonyl CoA, leading to severe metabolic crises and clinical complications. A significant proportion of total propionate production occurs in the gut microbiota and therefore the gut microbiota has been identified as a modifiable target. The use of oral antibiotics to reduce propionate production is a common approach, but it should be noted that long-term antibiotic use can lead to the formation of antibiotic-resistant strains in patients, disruption of the normal gut microbiota, and central nervous system toxicity. Constipation is a chronic problem in this patient population and can interfere with propionate production. New and more effective disease management approaches are needed to reduce the propionate burden and address these clinical issues. This review summarizes the potential contribution of gut-related factors in PA/MMA and addresses gut microbiota modification as a management approach.

Anahtar Kelimeler

• Propionic acidemia
• methylmalonic acidemia
• microbiota

Kaynakça

1. Agarwal, A., Kanekar, S., Sabat, S., & Thamburaj, K. (2016). Metronidazole-induced cerebellar toxicity. Neurology international, 8(1), 6365-6370.
2. Arora, T., Sharma, R., & Frost, G. (2011). Propionate. Anti-obesity and satiety enhancing factor? Appetite, 56(2), 511-515.
3. Asano, I., Hamaguchi, K., Fujii, S., & IINO, H. (2003). In vitro digestibility and fermentation of mannooligosaccharides from coffee mannan. Food Science and Technology Research, 9(1), 62-66.
4. Baumgartner, M. R., Hörster, F., Dionisi-Vici, C., Haliloglu, G., Karall, D., Chapman, K. A., . . . Ballhausen, D. (2014). Proposed guidelines for the diagnosis and management of methylmalonic and propionic acidemia. Orphanet journal of rare diseases, 9(1), 1-36.
5. Belenguer, A., Duncan, S. H., Holtrop, G., Anderson, S. E., Lobley, G. E., & Flint, H. J. (2007). Impact of pH on lactate formation and utilization by human fecal microbial communities. Applied and environmental microbiology, 73(20), 6526-6533.
6. Bordugo, A., Salvetti, E., Rodella, G., Piazza, M., Dianin, A., Amoruso, A., . . . Vitulo, N. (2021). Assessing gut microbiota in an infant with congenital propionic acidemia before and after probiotic supplementation. Microorganisms, 9(12), 2599.
7. Burlina, A., Tims, S., van Spronsen, F., Sperl, W., Burlina, A. P., Kuhn, M., . . . MacDonald, A. (2018). The potential role of gut microbiota and its modulators in the management of propionic and methylmalonic acidemia. Expert Opinion on Orphan Drugs, 6(11), 683-692. doi:10.1080/21678707.2018.1536540
8. Chapman, K. A., Gropman, A., MacLeod, E., Stagni, K., Summar, M. L., Ueda, K., . . . Matern, D. (2012). Acute management of propionic acidemia. Molecular genetics and metabolism, 105(1), 16-25.

9. Cheng, H.-H., & Lai, M.-H. (2000). Fermentation of resistant rice starch produces propionate reducing serum and hepatic cholesterol in rats. The Journal of nutrition, 130(8), 1991-1995. Daly, A., Evans, S., Ashmore, C., Chahal, S., Santra, S., & MacDonald, A. (2017a). The challenge of nutritional profiling of a protein‐free feed module for children on low protein tube feeds with organic acidaemias. Journal of Human Nutrition and Dietetics, 30(3), 292-301.
10. Daly, A., Evans, S., Ashmore, C., Chahal, S., Santra, S., & MacDonald, A. (2017b). Refining low protein modular feeds for children on low protein tube feeds with organic acidaemias. Molecular genetics and metabolism reports, 13, 99-104.
11. Daly, A., Evans, S., Gerrard, A., Santra, S., Vijay, S., & MacDonald, A. (2015). The nutritional intake of patients with organic acidaemias on enteral tube feeding: can we do better? In JIMD Reports, Volume 28 (pp. 29-39): Springer.
12. Daly, A., Pinto, A., Evans, S., Almeida, M., Assoun, M., Belanger-Quintana, A., . . . Champion, H. (2017). Dietary practices in propionic acidemia: a European survey. Molecular genetics and metabolism reports, 13, 83-89.
13. Duncan, S. H., Louis, P., Thomson, J. M., & Flint, H. J. (2009). The role of pH in determining the species composition of the human colonic microbiota. Environmental microbiology, 11(8), 2112-2122.
14. Ferket, P., Parks, C., & Grimes, J. (2002). Benefits of dietary antibiotic and mannanoligosaccharide supplementation for poultry. Paper presented at the Multi-State Poultry Meeting. 14:1–22.
15. Fernandes, J., Rao, A. V., & Wolever, T. M. (2000). Different substrates and methane producing status affect short-chain fatty acid profiles produced by in vitro fermentation of human feces. The Journal of nutrition, 130(8), 1932-1936.
16. Ferrer, M., Méndez-García, C., Rojo, D., Barbas, C., & Moya, A. (2017). Antibiotic use and microbiome function. Biochemical pharmacology, 134, 114-126.
17. Fleming, S. E., Fitch, M. D., & Chansler, M. W. (1989). High-fiber diets: influence on characteristics of cecal digesta including short-chain fatty acid concentrations and pH. The American journal of clinical nutrition, 50(1), 93-99.
18. Fowler, B., Leonard, J., & Baumgartner, M. (2008). Causes of and diagnostic approach to methylmalonic acidurias. Journal of Inherited Metabolic Disease: Official Journal of the Society for the Study of Inborn Errors of Metabolism, 31(3), 350-360.
19. Fraser, J. L., & Venditti, C. P. (2016). Methylmalonic and propionic acidemias: clinical management update. Current opinion in pediatrics, 28(6), 682.
20. Grootaert, C., Van den Abbeele, P., Marzorati, M., Broekaert, W. F., Courtin, C. M., Delcour, J. A., . . . Van de Wiele, T. (2009). Comparison of prebiotic effects of arabinoxylan oligosaccharides and inulin in a simulator of the human intestinal microbial ecosystem. FEMS microbiology ecology, 69(2), 231-242.
21. Hascoët, J.-M., Hubert, C., Rochat, F., Legagneur, H., Gaga, S., Emady-Azar, S., & Steenhout, P. G. (2011). Effect of formula composition on the development of infant gut microbiota. Journal of pediatric gastroenterology and nutrition, 52(6), 756-762.
22. Hossain, M. Z., Abe, J.-i., & Hizukuri, S. (1996). Multiple forms of β-mannanase from Bacillus sp. KK01. Enzyme and Microbial Technology, 18(2), 95-98.
23. Høverstad, T., Carlstedt-Duke, B., Lingaas, E., Midtvedt, T., Norin, K., Saxerholt, H., & Steinbakk, M. (1986). Influence of ampicillin, clindamycin, and metronidazole on faecal excretion of short-chain fatty acids in healthy subjects. Scandinavian journal of gastroenterology, 21(5), 621-626.
24. Høverstad, T., Carlstedt-Duke, B., Lingaas, E., Norin, E., Saxerholt, H., Steinbakk, M., & Midtvedt, T. (1986). Influence of oral intake of seven different antibiotics on faecal short-chain fatty acid excretion in healthy subjects. Scandinavian journal of gastroenterology, 21(8), 997-1003.
25. Jakobsson, H. E., Jernberg, C., Andersson, A. F., Sjölund-Karlsson, M., Jansson, J. K., & Engstrand, L. (2010). Short-term antibiotic treatment has differing long-term impacts on the human throat and gut microbiome. PloS one, 5(3), e9836.
26. Jie, Z., Bang-yao, L., Ming-Jie, X., Hai-wei, L., Zu-kang, Z., Ting-song, W., & Craig, S. A. (2000). Studies on the effects of polydextrose intake on physiologic functions in Chinese people. The American journal of clinical nutrition, 72(6), 1503-1509.
27. Knol, J., Scholtens, P., Kafka, C., Steenbakkers, J., Gro, S., Helm, K., . . . Wells, J. (2005). Colon microflora in infants fed formula with galacto-and fructo-oligosaccharides: more like breast-fed infants. Journal of pediatric gastroenterology and nutrition, 40(1), 36-42.
28. Koeth, R. A., Wang, Z., Levison, B. S., Buffa, J. A., Org, E., Sheehy, B. T., . . . Li, L. (2013). Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nature medicine, 19(5), 576-585.
29. Leonard, J. (1997). Stable isotope studies in propionic and methylmalonic acidaemia. European journal of pediatrics, 156(1), S67-S69.
30. Lopez, H. W., Levrat, M.-A., Guy, C., Messager, A., Demigné, C., & Rémésy, C. (1999). Effects of soluble corn bran arabinoxylans on cecal digestion, lipid metabolism, and mineral balance (Ca, Mg) in rats. The Journal of nutritional biochemistry, 10(9), 500-509.
31. Macfarlane, G. T., & Gibson, G. R. (1997). Carbohydrate fermentation, energy transduction and gas metabolism in the human large intestine. In Gastrointestinal microbiology (pp. 269-318): Springer.
32. Mäkeläinen, H., Mäkivuokko, H., Salminen, S., Rautonen, N., & Ouwehand, A. (2007). The effects of polydextrose and xylitol on microbial community and activity in a 4‐stage colon simulator. Journal of Food Science, 72(5), M153-M159.
33. Michel, C., Benard, C., Lahaye, M., Formaglio, D., Kaeffer, B., Quemener, B., . . . Cherbut, C. (1999). Algal oligosaccharides as functional foods: in vitro study of their cellular and fermentative effects. Sciences des Aliments (France). Journal of Food Science , 19, 311–332
34. Niemi, A.-K., Kim, I. K., Krueger, C. E., Cowan, T. M., Baugh, N., Farrell, R., . . . Enns, G. M. (2015). Treatment of methylmalonic acidemia by liver or combined liver-kidney transplantation. The Journal of Pediatrics, 166(6), 1455-1461.
35. O'Keefe, S. J. (2010). Tube feeding, the microbiota, and Clostridium difficile infection. World journal of gastroenterology: WJG, 16(2), 139.
36. Oozeer, R., van Limpt, K., Ludwig, T., Ben Amor, K., Martin, R., Wind, R. D., . . . Knol, J. (2013). Intestinal microbiology in early life: specific prebiotics can have similar functionalities as human-milk oligosaccharides. The American journal of clinical nutrition, 98(2), 561S-571S.
37. Prasad, C., Nurko, S., Borovoy, J., & Korson, M. S. (2004). The importance of gut motility in the metabolic control of propionic acidemia. The Journal of Pediatrics, 144(4), 532-535.
38. Reichardt, N., Duncan, S. H., Young, P., Belenguer, A., Leitch, C. M., Scott, K. P., . . . Louis, P. (2014). Phylogenetic distribution of three pathways for propionate production within the human gut microbiota. The ISME journal, 8(6), 1323-1335.
39. Sloan, J. L., Manoli, I., & Venditti, C. P. (2015). Liver or combined liver-kidney transplantation for patients with isolated methylmalonic acidemia: who and when? The Journal of Pediatrics, 166(6), 1346-1350.
40. Sun, Y., & O’Riordan, M. X. (2013). Regulation of bacterial pathogenesis by intestinal short-chain fatty acids. In Advances in applied microbiology, 85, 93-118.
41. Sutton, V. R., Chapman, K. A., Gropman, A. L., MacLeod, E., Stagni, K., Summar, M. L., . . . Island, E. (2012). Chronic management and health supervision of individuals with propionic acidemia. Molecular genetics and metabolism, 105(1), 26-33.
42. Takeshita, T., Yasui, M., Tomioka, M., Nakano, Y., Shimazaki, Y., & Yamashita, Y. (2011). Enteral tube feeding alters the oral indigenous microbiota in elderly adults. Applied and environmental microbiology, 77(19), 6739-6745.
43. Thompson, G., Chalmers, R., Walter, J., Bresson, J., Lyonnet, S., Reed, P., . . . Halliday, D. (1990). The use of metronidazole in management of methylmalonic and propionic acidaemias. European journal of pediatrics, 149(11), 792-796.
44. Van De Wiele, T., Boon, N., Possemiers, S., Jacobs, H., & Verstraete, W. (2007). Inulin‐type fructans of longer degree of polymerization exert more pronounced in vitro prebiotic effects. Journal of Applied Microbiology, 102(2), 452-460.
45. Vinolo, M. A., Rodrigues, H. G., Nachbar, R. T., & Curi, R. (2011). Regulation of inflammation by short chain fatty acids. Nutrients, 3(10), 858-876.
46. Vogt, J. A., Pencharz, P. B., & Wolever, T. M. (2004). L-Rhamnose increases serum propionate in humans. The American journal of clinical nutrition, 80(1), 89-94.
47. Walker, A. W., Duncan, S. H., Leitch, E. C. M., Child, M. W., & Flint, H. J. (2005). pH and peptide supply can radically alter bacterial populations and short-chain fatty acid ratios within microbial communities from the human colon. Applied and environmental microbiology, 71(7), 3692-3700.