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Gut microbial metabolism of dietary fibre protects against high energy feeding induced ovarian follicular atresia in a pig model

  • Yong Zhuo (a1), Meng Cao (a1), Yuechan Gong (a1), Lianchao Tang (a1), Xuemei Jiang (a1), Yang Li (a1), Min Yang (a1), Shengyu Xu (a1), Jian Li (a1), Lianqiang Che (a1), Yan Lin (a1), Bin Feng (a1), Zhengfeng Fang (a1) and De Wu (a1)...


To investigate the effects of dietary fibre on follicular atresia in pigs fed a high-fat diet, we fed thirty-two prepubescent gilts a basal diet (CON) or a CON diet supplemented with 300 g/d dietary fibre (fibre), 240 g/d soya oil (SO) or both (fibre + SO). At the 19th day of the 4th oestrus cycle, gilts fed the SO diet showed 112 % more atretic follicles and greater expression of the apoptotic markers, Bax and caspase-3, and these effects were reversed by the fibre diet. The abundance of SCFA-producing microbes was decreased by the SO diet, but this effect was reversed by fibre treatment. Concentrations of serotonin and melatonin in the serum and follicular fluid were increased by the fibre diet. Overall, dietary fibre protected against high fat feeding-induced follicular atresia at least partly via gut microbiota-related serotonin–melatonin synthesis. These results provide insight into preventing negative effects on fertility in humans consuming a high-energy diet.


Corresponding author

*Corresponding author: De Wu, fax +86-028-86290922, email


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These authors contributed equally to this work.



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1.Ng, M, Fleming, T, Robinson, M, et al. (2014) Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 384, 766781.
2.Broughton, DE & Moley, KH (2017) Obesity and female infertility: potential mediators of obesity’s impact. Fertil Steril 107, 840847.
3.Myers, M, Britt, KL, Wreford, NG, et al. (2004) Methods for quantifying follicular numbers within the mouse ovary. Reproduction 127, 569580.
4.Kelsey, TW, Anderson, RA, Wright, P, et al. (2011) Data-driven assessment of the human ovarian reserve. Mol Hum Reprod 18, 7987.
5.Machtinger, R, Combelles, CM, Missmer, SA, et al. (2012) The association between severe obesity and characteristics of failed fertilized oocytes. Hum Reprod 27, 31983207.
6.Shah, DK, Missmer, SA, Berry, KF, et al. (2011) Effect of obesity on oocyte and embryo quality in women undergoing in vitro fertilization. Obstet Gynecol 118, 6370.
7.Wang, N, Luo, LL, Xu, JJ, et al. (2014) Obesity accelerates ovarian follicle development and follicle loss in rats. Metabolism 63, 94103.
8.Zhang, H, Liu, L, Li, X, et al. (2014) Life-long in vivo cell-lineage tracing shows that no oogenesis originates from putative germline stem cells in adult mice. Proc Natl Acad Sci U S A 111, 1798317988.
9.Zhang, H, Panula, S, Petropoulos, S, et al. (2015) Adult human and mouse ovaries lack DDX4-expressing functional oogonial stem cells. Nat Med 21, 11161118.
10.Papathanasopoulos, A & Camilleri, M (2010) Dietary fiber supplements: effects in obesity and metabolic syndrome and relationship to gastrointestinal functions. Gastroenterology 138, 6572.
11.Liu, S, Willett, WC, Manson, JE, et al. (2003) Relation between changes in intakes of dietary fiber and grain products and changes in weight and development of obesity among middle-aged women. Am J Clin Nutr 78, 920927.
12.Mayengbam, S, Lambert, JE, Parnell, JA, et al. (2017) Dietary fiber supplementation normalizes serum metabolites of adults with overweight/obesity in a 12-week randomized control trial. FASEB J 31, Suppl. 1, 433435.
13.Han, S, Jiao, J, Zhang, W, et al. (2015) Dietary fiber prevents obesity-related liver lipotoxicity by modulating sterol-regulatory element binding protein pathway in C57BL/6J mice fed a high-fat/cholesterol diet. Sci Rep 5, 15256.
14.Jarrett, S & Ashworth, CJ (2018) The role of dietary fibre in pig production, with a particular emphasis on reproduction. J Anim Sci Biotechnol 9, 59.
15.Ferguson, EM, Slevin, J, Hunter, MG, et al. (2007) Beneficial effects of a high fibre diet on oocyte maturity and embryo survival in gilts. Reproduction 133, 433439.
16.Weaver, AC, Kelly, JM, Kind, KL, et al. (2013) Oocyte maturation and embryo survival in nulliparous female pigs (gilts) is improved by feeding a lupin-based high-fibre diet. Reprod Fertil Dev 25, 12161223.
17.Gaskins, AJ, Mumford, SL, Zhang, C, et al. (2009) Effect of daily fiber intake on reproductive function: the BioCycle Study. Am J Clin Nutr 90, 10611069.
18.Nagel, G, Altenburg, HP, Nieters, A, et al. (2005) Reproductive and dietary determinants of the age at menopause in EPIC-Heidelberg. Maturitas 52, 337347.
19.Heinritz, SN, Weiss, E, Eklund, M, et al. (2016) Intestinal microbiota and microbial metabolites are changed in a pig model fed a high-fat/low-fiber or a low-fat/high-fiber diet. PLOS ONE 11, e154329.
20.Koh, A, De Vadder, F, Kovatcheva-Datchary, P, et al. (2016) From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell 165, 13321345.
21.Shajib, MS, Baranov, A & Khan, W (2017) Diverse effects of gut-derived serotonin in intestinal inflammation. ACS Chem Neurosci 8, 920931.
22.Zhou, P, Zhao, Y, Zhang, P, et al. (2017) Microbial mechanistic insight into the role of inulin in improving maternal health in a pregnant sow model. Front Microbiol 8, 2242.
23.Yano, JM, Yu, K, Donaldson, GP, et al. (2015) Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 161, 264276.
24.Koren, Z, Pfeifer, Y & Sulman, FG (1965) Serotonin. Content of human placenta and fetus during pregnancy. Am J Obstet Gynecol 93, 411415.
25.Tomy, S, Saikrithi, P, James, N, et al. (2016) Serotonin induced changes in the expression of ovarian gene network in the Indian white shrimp, Penaeus indicus. Aquaculture 452, 239246.
26.Santhoshi, S, Sugumar, V & Munuswamy, N (2009) Serotonergic stimulation of ovarian maturation and hemolymph vitellogenin in the Indian white shrimp, Fenneropenaeus indicus. Aquaculture 291, 192199.
27.Wongprasert, K, Asuvapongpatana, S, Poltana, P, et al. (2006) Serotonin stimulates ovarian maturation and spawning in the black tiger shrimp Penaeus monodon. Aquaculture 261, 14471454.
28.Meeratana, P, Withyachumnarnkul, B, Damrongphol, P, et al. (2006) Serotonin induces ovarian maturation in giant freshwater prawn broodstock, Macrobrachium rosenbergii de Man. Aquaculture 260, 315325.
29.Prasad, P, Ogawa, S & Parhar, IS (2015) Role of serotonin in fish reproduction. Front Neurosci 9, 195.
30.Azmitia, EC (2001) Modern views on an ancient chemical: serotonin effects on cell proliferation, maturation, and apoptosis. Brain Res Bull 56, 413424.
31.Nebigil, CG, Etienne, N, Messaddeq, N, et al. (2003) Serotonin is a novel survival factor of cardiomyocytes: mitochondria as a target of 5-HT2B receptor signaling. FASEB J 17, 13731375.
32.Banasr, M, Hery, M, Printemps, R, et al. (2004) Serotonin-induced increases in adult cell proliferation and neurogenesis are mediated through different and common 5-HT receptor subtypes in the dentate gyrus and the subventricular zone. Neuropsychopharmacology 29, 450460.
33.Han, X, Chen, C, Cheng, G, et al. (2015) Peroxisome proliferator-activated receptor γ attenuates serotonin-induced pulmonary artery smooth muscle cell proliferation and apoptosis inhibition involving ERK1/2 pathway. Microvasc Res 100, 1724.
34.Gurbuz, N, Asoglu, MR, Ashour, AA, et al. (2016) A selective serotonin 5-HT1B receptor inhibition suppresses cells proliferation and induces apoptosis in human uterine leiomyoma cells. Eur J Obstet Gynecol Reprod Biol 206, 114119.
35.Hadden, C, Fahmi, T, Cooper, A, et al. (2017) Serotonin transporter protects the placental cells against apoptosis in caspase 3-independent pathway. J Cell Physiol 232, 35203529.
36.Mercado, CP, Byrum, S, Beggs, ML, et al. (2013) Impact of elevated plasma serotonin on global gene expression of murine megakaryocytes. PLOS ONE 8, e72580.
37.Spurlock, ME & Gabler, NK (2008) The development of porcine models of obesity and the metabolic syndrome. J Nutr 138, 397402.
38.Monniaux, D, Clément, F, Dalbiès-Tran, R, et al. (2014) The ovarian reserve of primordial follicles and the dynamic reserve of antral growing follicles: what is the link? Biol Reprod 85, 111.
39.Griffin, J, Emery, BR & Huang, I (2006) Comparative analysis of follicle morphology and oocyte diameter in four mammalian species (mouse, hamster, pig, and human). J Exp Clin Assist Reprod 3, 2.
40.Zhuo, Y, Shi, X, Lv, G, et al. (2017) Beneficial effects of dietary soluble fiber supplementation in replacement gilts: pubertal onset and subsequent performance. Anim Reprod Sci 186, 1120.
41.Wu, D, Cheung, QC, Wen, L, et al. (2006) A growth-maturation system that enhances the meiotic and developmental competence of porcine oocytes isolated from small follicles. Biol Reprod 75, 547554.
42.Zhuo, Y, Hua, L, Feng, B, et al. (2019) Fibroblast growth factor 21 coordinates adiponectin to mediate the beneficial effects of low-protein diet on primordial follicle reserve. EBioMedicine 41, 623635.
43.Zhuo, Y, Feng, B, Xuan, Y, et al. (2020) Inclusion of purified dietary fiber during gestation improved the reproductive performance of sows. J Animal Sci Biotechnol 11, 47.
44.van den Hurk, R & Zhao, J (2005) Formation of mammalian oocytes and their growth, differentiation and maturation within ovarian follicles. Theriogenology 63, 17171751.
45.McGee, EA & Hsueh, AJ (2000) Initial and cyclic recruitment of ovarian follicles. Endocr Rev 21, 200214.
46.Reynolds, KA, Boudoures, AL, Chi, MMY, et al. (2015) Adverse effects of obesity and/or high-fat diet on oocyte quality and metabolism are not reversible with resumption of regular diet in mice. Reprod Fertil Dev 27, 716.
47.Skaznik-Wikiel, ME, Swindle, DC, Allshouse, AA, et al. (2016) High-fat diet causes subfertility and compromised ovarian function independent of obesity in mice. Biol Reprod 108, 110.
48.Sommer, F & Bäckhed, F (2013) The gut microbiota – masters of host development and physiology. Nat Rev Microbiol 11, 227238.
49.Baquero, F & Nombela, C (2012) The microbiome as a human organ. Clin Microbiol Infect 18, 24.
50.Sjögren, K, Engdahl, C, Henning, P, et al. (2012) The gut microbiota regulates bone mass in mice. J Bone Miner Res 27, 13571367.
51.Doré, J & Blottière, H (2015) The influence of diet on the gut microbiota and its consequences for health. Curr Opin Biotech 32, 195199.
52.Ussar, S, Griffin, NW, Bezy, O, et al. (2015) Interactions between gut microbiota, host genetics and diet modulate the predisposition to obesity and metabolic syndrome. Cell Metab 22, 516530.
53.Boulangé, CL, Neves, AL, Chilloux, J, et al. (2016) Impact of the gut microbiota on inflammation, obesity, and metabolic disease. Genome Med 8, 42.
54.Desai, MS, Seekatz, AM, Koropatkin, NM, et al. (2016) A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell 167, 13391353.
55.Li, X, Guo, J, Ji, K, et al. (2016) Bamboo shoot fiber prevents obesity in mice by modulating the gut microbiota. Sci Rep 6, 32953.
56.Ivarsson, E, Roos, S, Liu, HY, et al. (2014) Fermentable non-starch polysaccharides increases the abundance of Bacteroides–Prevotella–Porphyromonas in ileal microbial community of growing pigs. Animal 8, 17771787.
57.Xia, X, Li, G, Ding, Y, et al. (2017) Effect of whole grain qingke (Tibetan Hordeum vulgare L. Zangqing 320) on the serum lipid levels and intestinal microbiota of rats under high-fat diet. J Agric Food Chem 65, 26862693.
58.Song, JJ, Tian, WJ, Kwok, L, et al. (2017) Effects of microencapsulated Lactobacillus plantarum LIP-1 on the gut microbiota of hyperlipidaemic rats. Br J Nutr 118, 481492.
59.Zhou, Z, Zheng, W, Shang, W, et al.(2015) How host gender affects the bacterial community in pig feces and its correlation to skatole production. Ann Microbiol 65, 23792386.
60.Roager, HM & Licht, TR (2018) Microbial tryptophan catabolites in health and disease. Nat Commun 9, 3294.
61.Ríos-Covián, D, Ruas-Madiedo, P, Margolles, A, et al. (2016) Intestinal short chain fatty acids and their link with diet and human health. Front Microbiol 7, 185.
62.Schroeder, BO, Birchenough, GMH, Ståhlman, M, et al. (2018) Bifidobacteria or fiber protects against diet-induced microbiota-mediated colonic mucus deterioration. Cell Host Microbe 23, 2740.
63.Montoya, CA, Rutherfurd, SM & Moughan, PJ (2016) Kiwifruit fibre level influences the predicted production and absorption of SCFA in the hindgut of growing pigs using a combined in vivo–in vitro digestion methodology. Br J Nutr 115, 13171324.
64.Reigstad, CS, Salmonson, CE, Rainey, JF, et al. (2015) Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells. FASEB J 29, 13951403.
65.Hirshfield, AN (1991) Development of follicles in the mammalian ovary. Int Rev Cytol 124, 43101.
66.Palumbo, A & Yeh, J (1994) In situ localization of apoptosis in the rat ovary during follicular atresia. Biol Reprod 51, 888895.
67.Craig, J, Orisaka, M, Wang, H, et al. (2007) Gonadotropin and intra-ovarian signals regulating follicle development and atresia: the delicate balance between life and death. Front Biosci 12, 36283639.
68.Regan, SLP, Knight, PG, Yovich, JL, et al. (2018) Granulosa cell apoptosis in the ovarian follicle – a changing view. Front Endocrinol 9, 61.
69.Kroemer, G & Reed, JC (2000) Mitochondrial control of cell death. Nat Med 6, 513519.
70.Green, DR & Reed, JC (1998) Mitochondria and apoptosis. Science 281, 13091312.
71.Adams, JM & Cory, S (2001) Life-or-death decisions by the Bcl-2 protein family. Trends Biochem Sci 26, 6166.
72.Jin, CJ, Engstler, AJ, Sellmann, C, et al. (2016) Sodium butyrate protects mice from the development of the early signs of non-alcoholic fatty liver disease: role of melatonin and lipid peroxidation. Br J Nutr 116, 16821693.
73.Fernando, S & Rombauts, L (2014) Melatonin: shedding light on infertility? – a review of the recent literature. J Ovarian Res 7, 98.
74.Tamura, H, Takasaki, A, Taketani, T, et al. (2013) Melatonin as a free radical scavenger in the ovarian follicle. Endocr J 60, 113.


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Gut microbial metabolism of dietary fibre protects against high energy feeding induced ovarian follicular atresia in a pig model

  • Yong Zhuo (a1), Meng Cao (a1), Yuechan Gong (a1), Lianchao Tang (a1), Xuemei Jiang (a1), Yang Li (a1), Min Yang (a1), Shengyu Xu (a1), Jian Li (a1), Lianqiang Che (a1), Yan Lin (a1), Bin Feng (a1), Zhengfeng Fang (a1) and De Wu (a1)...


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