Sulfur-containing amino acid supplementation to gilts from late pregnancy to lactation altered offspring’s intestinal microbiota and plasma metabolites

  • 113 Accesses


Maternal nutrition during late pregnancy and lactation is highly involved with the offspring’s health status. The study was carried out to evaluate the effects of different ratios of methionine and cysteine (Met/Cys: 46% Met, 51% Met, 56% Met, and 62% Met; maintained with 0.78% of total sulfur-containing amino acids; details in “Materials and methods”) supplements in the sows’ diet from late pregnancy to lactation on offspring’s plasma metabolomics and intestinal microbiota. The results revealed that the level of serum albumin, calcium, iron, and magnesium was increased in the 51% Met group compared with the 46% Met, 56% Met, and 62% Met groups. Plasma metabolomics results indicated that the higher ratios of methionine and cysteine (0.51% Met, 0.56% Met, and 0.62% Met)–supplemented groups enriched the level of hippuric acid, retinoic acid, riboflavin, and δ-tocopherol than in the 46% Met group. Furthermore, the 51% Met–supplemented group had a higher relative abundance of Firmicutes compared with the other three groups (P < 0.05), while the 62% Met–supplemented group increased the abundance of Proteobacteria compared with the other three groups (P < 0.05) in piglets’ intestine. These results indicated that a diet consisting with 51% Met is the optimum Met/Cys ratio from late pregnancy to lactation can maintain the offspring’s health by improving the serum biochemical indicators and altering the plasma metabolomics profile and intestinal gut microbiota composition, but higher proportion of Met/Cys may increase the possible risk to offspring’s health.

This is a preview of subscription content, log in to check access.

Access options

Buy single article

Instant unlimited access to the full article PDF.

US$ 39.95

Price includes VAT for USA

Subscribe to journal

Immediate online access to all issues from 2019. Subscription will auto renew annually.

US$ 199

This is the net price. Taxes to be calculated in checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7


  1. Aiello SE (2016) Serum proteins and the dysproteinmias. The Merk veterinary manual. Merk & Co. Inc, Kenilworth, pp 3173–3174

  2. Azad MAK, Bin P, Liu G, Fang J, Li T, Yin Y (2018a) Effects of different methionine levels on offspring piglets during late gestation and lactation. Food Funct 9(11):5843–5854.

  3. Azad MAK, Sarker M, Li T, Yin J (2018b) Probiotic species in the modulation of gut microbiota: an overview. Biomed Res Int 2018:9478630.

  4. Barbalho SM, Goulart RA, Batista G (2019) Vitamin A and inflammatory bowel diseases: from cellular studies and animal models to human disease. Expert Rev Gastroenterol Hepatol 13(1):25–35.

  5. Buchet A, Belloc C, Leblanc-Maridor M, Merlot E (2017) Effects of age and weaning conditions on blood indicators of oxidative status in pigs. PLoS One 12(5):e0178487.

  6. Chen L, Xu Y, Chen X, Fang C, Zhao L, Chen F (2017) The maturing development of gut microbiota in commercial piglets during the weaning transition. Front Microbiol 8:1688.

  7. da Silva BP, Toledo RCL, Grancieri M, Moreira MEC, Medina NR, Silva RR, Costa NMB, Martino HSD (2019) Effects of chia (Salvia hispanica L.) on calcium bioavailability and inflammation in Wistar rats. Food Res Int 116:592–599.

  8. Dallanora D, Marcon J, Walter MP, Biondo N, Bernardi ML, Wentz I, Bortolozzo FP (2017) Effect of dietary amino acid supplementation during gestation on placental efficiency and litter birth weight in gestating gilts. Livest Sci 197:30–35.

  9. De Feo P, Horber FF, Haymnd MW (1992) Meal stimulation of albumin synthesis: a significant contributor to whole body protein synthesis in humans. Am J Physiol Endocrinol Metab 263:E794–E799.

  10. Ding S, Azad MAK, Fang J, Zhou X, Xu K, Yin Y, Liu G (2019a) Impact of sulfur-containing amino acids on the plasma metabolomics and intestinal microflora of the sow in late pregnancy. Food Funct 10:5910.

  11. Ding S, Fang J, Liu G, Veeramuthu D, Naif Abdullah AD, Yin Y (2019b) The impact of different levels of cysteine on the plasma metabolomics and intestinal microflora of sows from late pregnancy to lactation. Food Funct 10(2):691–702.

  12. Fang Z, Yao K, Zhang X, Zhao S, Sun Z, Tian G, Yu B, Lin Y, Zhu B, Jia G, Zhang K, Chen D, Wu D (2010) Nutrition and health relevant regulation of intestinal sulfur amino acid metabolism. Amino Acids 39(3):633–640.

  13. Fontana M, Pecci L, Duprè S, Cavallini DJNR (2004) Antioxidant properties of sulfinates: protective effect of hypotaurine on peroxynitrite-dependent damage. Neurochem Res 29(1):111–116.

  14. Frese SA, Parker K, Calvert CC, Mills DA (2015) Diet shapes the gut microbiome of pigs during nursing and weaning. Microbiome 3:28.

  15. Fukumori C, Casaro MB, Thomas AM, Mendes E, Ribeiro WR, Crisma AR, Murata GM, Bizzarro B, Dias-Neto E, Setubal JC, Oliveira MA, Tavares-de-Lima W, Curi R, Bordin S, Sartorelli P, Ferreira CM (2019) Maternal supplementation with a synbiotic has distinct outcomes on offspring gut microbiota formation in A/J and C57BL/6 mice, differentially affecting airway inflammatory cell infiltration and mucus production. J Funct Foods 61.

  16. Gao J, Yang H, Chen J, Fang J, Chen C, Liang R, Yang G, Wu H, Wu C, Li S (2013) Analysis of serum metabolites for the discovery of amino acid biomarkers and the effect of galangin on cerebral ischemia. Mol BioSyst 9(9):2311–2321.

  17. Garlick PJ (2006) Toxicity of methionine in humans. Nutr J 136(6):1722S–1725S.

  18. Herring CM, Bazer FW, Johnson GA, Wu G (2018) Impacts of maternal dietary protein intake on fetal survival, growth, and development. Exp Biol Med (Maywood) 243(6):525–533.

  19. Hooper LV, Macpherson AJ (2010) Immune adaptations that maintain homeostasis with the intestinal microbiota. Nat Rev Immunol 10:159–169.

  20. Hou Y, Wu G (2018) L-glutamate nutrition and metabolism in swine. Amino Acids 50(11):1497–1510.

  21. Hsu CN, Tain YL (2019) The good, the bad, and the ugly of pregnancy nutrients and developmental programming of adult disease. Nutrients 11(4).

  22. Huang C, Chiba LI, Magee WE, Wang Y, Griffing DA, Torres IM, Rodning SP, Bratcher CL, Bergen WG, Spangler EA (2019) Effect of flaxseed oil, animal fat, and vitamin E supplementation on growth performance, serum metabolites, and carcass characteristics of finisher pigs, and physical characteristics of pork. Livest Sci 220:143–151.

  23. Isaacson R, Kim HB (2012) The intestinal microbiome of the pig. Anim Health Res Rev 13(1):100–109.

  24. Janowski A, Kolb R, Zhang W, Sutterwala F (2013) Beneficial and detrimental roles of NLRs in carcinogenesis. Front Immunol 4(370).

  25. Kalhan SC (2016) One carbon metabolism in pregnancy: impact on maternal, fetal and neonatal health. Mol Cell Endocrinol 435:48–60.

  26. Kovacs CS (2016) Maternal mineral and bone metabolism during pregnancy, lactation, and post-weaning recovery. Physiol Rev 96(2):449–547.

  27. Lauridsen C, Jensen SK (2005) Influence of supplementation of all-rac-α-tocopheryl acetate preweaning and vitamin C postweaning on α-tocopherol and immune responses of piglets. Anim Sci J 83(6):1274–1286.

  28. Li Y, Guo Y, Wen Z, Jiang X, Ma X, Han X (2018) Weaning stress perturbs gut microbiome and its metabolic profile in piglets. Sci Rep 8(1):18068.

  29. Liang H, Dai Z, Kou J, Sun K, Chen J, Yang Y, Wu G, Wu Z (2018) Dietary L-tryptophan supplementation enhances the intestinal mucosal barrier function in weaned piglets: implication of tryptophan-metabolizing microbiota. Int J Mol Sci 20(1).

  30. Liu D, Zong EY, Huang PF, Yang HS, Yan SL, Li JZ, Li YL, Ding XQ, He SP, Xiong X, Yin YL (2019) The effects of dietary sulfur amino acids on serum biochemical variables, mucosal amino acid profiles, and intestinal inflammation in weaning piglets. Livest Sci 220:32–36.

  31. MacKay DS, Brophy JD, McBreairty LE, McGowan RA, Bertolo RF (2012) Intrauterine growth restriction leads to changes in sulfur amino acid metabolism, but not global DNA methylation, in Yucatan miniature piglets. J Nutr Biochem 23(9):1121–1127.

  32. Martin Agnoux A, Antignac JP, Boquien CY, David A, Desnots E, Ferchaud-Roucher V, Darmaun D, Parnet P, Alexandre-Gouabau MC (2015) Perinatal protein restriction affects milk free amino acid and fatty acid profile in lactating rats: potential role on pup growth and metabolic status. J Nutr Biochem 26(7):784–795.

  33. Mennitti LV, Oliveira JL, Morais CA, Estadella D, Oyama LM, Oller do Nascimento CM, Pisani LP (2015) Type of fatty acids in maternal diets during pregnancy and/or lactation and metabolic consequences of the offspring. J Nutr Biochem 26(2):99–111.

  34. NRC (2012) Nutrient requirements of swine: eleventh revised edition. The National Academies Press, Washington, DC.

  35. Remus A, Hauschild L, Corrent E, Letourneau-Montminy MP, Pomar C (2019) Pigs receiving daily tailored diets using precision-feeding techniques have different threonine requirements than pigs fed in conventional phase-feeding systems. J Anim Sci Biotechnol 10:16.

  36. Robertson RC, Kaliannan K, Strain CR, Ross RP, Stanton C, Kang JX (2018) Maternal omega-3 fatty acids regulate offspring obesity through persistent modulation of gut microbiota. Microbiome 6(1):95.

  37. Sabui S, Kapadia R, Ghosal A, Schneider M, Lambrecht NWG, Said HM (2018) Biotin and pantothenic acid oversupplementation to conditional SLC5A6 KO mice prevents the development of intestinal mucosal abnormalities and growth defects. Am J Physiol Cell Physiol 315(1):C73–C79.

  38. Shoveller AK, Stoll B, Ball RO, Burrin DG (2005) Nutritional and functional importance of intestinal sulfur amino acid metabolism. Nutr J 135(7):1609–1612.

  39. Stipanuk MH, Dominy JE Jr, Lee J-I, Coloso RM (2006) Mammalian cysteine metabolism: new insights into regulation of cysteine metabolism. Nutr J 136(6):1652S–1659S.

  40. Suliman ME, Bárány P, Filho JCD, Lindholm B, Bergström J (2002) Accumulation of taurine in patients with renal failure. Nephrol Dial Transplant 17(3):528–529.

  41. Tesseraud S, Metayer Coustard S, Collin A, Seiliez I (2009) Role of sulfur amino acids in controlling nutrient metabolism and cell functions: implications for nutrition. Br J Nutr 101(8):1132–1139.

  42. Thakur K, Tomar SK, Singh AK, Mandal S, Arora S (2017) Riboflavin and health: a review of recent human research. Crit Rev Food Sci Nutr 57(17):3650–3660.

  43. Townsend DM, Tew KD, Tapiero H (2004) Sulfur containing amino acids and human disease. Biomed Pharmacother 58(1):47–55.

  44. Traber MG (2012) Vitamin E, vol 11th Ed. Lippincott Williams & Wilkins, Baltimore

  45. Trushina E, Dutta T, Persson XM, Mielke MM, Petersen RC (2013) Identification of altered metabolic pathways in plasma and CSF in mild cognitive impairment and Alzheimer's disease using metabolomics. PLoS One 8(5):e63644.

  46. Uruakpa FO, Ismond MAH, Akobundu ENT (2002) Colostrum and its benefits: a review. Nutr Res 22(6):755–767.

  47. van de Poll MCG, Dejong CHC, Soeters PB (2006) Adequate range for sulfur-containing amino acids and biomarkers for their excess: lessons from enteral and parenteral nutrition. Nutr J 136(6):1694S–1700S.

  48. Verheyen AJM, Maes DGD, Mateusen B, Deprez P, Janssens GPJ, Ld L, Counotte G (2007) Serum biochemical reference values for gestating and lactating sows. Vet J 174(1):92–98.

  49. Wei H, Zhao X, Xia M, Tan C, Gao J, Htoo JK, Xu C, Peng J (2019) Different dietary methionine to lysine ratios in the lactation diet: effects on the performance of sows and their offspring and methionine metabolism in lactating sows. J Anim Sci Biotechnol 10:76–11.

  50. Wu G (2016) Dietary protein intake and human health. Food Funct 7:1251–1265

  51. Xin Z, Pu L, Gao W, Wang Y, Wei J, Shi T, Yao Z, Guo C (2017) Riboflavin deficiency induces a significant change in proteomic profiles in HepG2 cells. Sci Rep 7:45861.

  52. Xu M, Che L, Gao K, Wang L, Yang X, Wen X, Jiang Z, Wu D (2019) Effects of dietary taurine supplementation to gilts during late gestation and lactation on offspring growth and oxidative stress. Animals (Basel) 9(5).

  53. Yi L, Shi S, Wang Y, Huang W, Xia ZA, Xing Z, Peng W, Wang Z (2016) Serum metabolic profiling reveals altered metabolic pathways in patients with post-traumatic cognitive impairments. Sci Rep 6:21320.

  54. Zhang ZH, Wei F, Vaziri ND, Cheng XL, Bai X, Lin RC, Zhao YY (2015) Metabolomics insights into chronic kidney disease and modulatory effect of rhubarb against tubulointerstitial fibrosis. Sci Rep 5:14472.

  55. Zhang S, Chen F, Zhang Y, Lv Y, Heng J, Min T, Li L, Guan W (2018) Recent progress of porcine milk components and mammary gland function. J Anim Sci Biotechnol 9:77–13.

  56. Zhang S, Heng J, Song H, Zhang Y, Lin X, Tian M, Chen F, Guan W (2019) Role of maternal dietary protein and amino acids on fetal programming, early neonatal development, and lactation in swine. Animals (Basel) 9(1).

  57. Zhong H, Li H, Liu G, Wan H, Mercier Y, Zhang X, Lin Y, Che L, Xu S, Tang L, Tian G, Chen D, Wu FZ (2016) Increased maternal consumption of methionine as its hydroxyl analog promoted neonatal intestinal growth without compromising maternal energy homeostasis. J Anim Sci Biotechnol 7:46.

Download references


The authors acknowledge the CAS-TWAS President’s Fellowship for international PhD students.

Funding information

This study was supported by National Natural Science Foundation of China (No. 31772642, 31672457), International Partnership Program of Chinese Academy of Sciences (161343KYSB20160008), Hunan Provincial Science and Technology Department (2017NK2322, 2018CT5002, 2018WK4025), Local Science and Technology Development Project guided by The Central Government (YDZX20184300002303), Double first-class construction project of Hunan Agricultural University (SYL201802003, YB2018007, CX20190497), Project for Yunnan Yin Yulong Academician Workstation from Yunan Province (2018IC087), and China Postdoctoral Science Foundation (2018 M632963, 2019 T120705).

Author information

Correspondence to Gang Liu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was carried out in accordance with the guidelines of the Laboratory Animal Ethical Commission of the Chinese Academy of Science and approved by the Animal Care Committee of the Institute of Subtropical Agriculture (201703-64C), Chinese Academy of Science, Changsha, China.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material


(PDF 171 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Azad, M.A.K., Liu, G., Bin, P. et al. Sulfur-containing amino acid supplementation to gilts from late pregnancy to lactation altered offspring’s intestinal microbiota and plasma metabolites. Appl Microbiol Biotechnol 104, 1227–1242 (2020).

Download citation


  • Sulfur-containing amino acids
  • Pregnancy
  • Lactation
  • Intestinal microbiota
  • Plasma metabolomics