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Original article
Gut commensal Parabacteroides goldsteinii plays a predominant role in the anti-obesity effects of polysaccharides isolated from Hirsutella sinensis
  1. Tsung-Ru Wu1,2,
  2. Chuan-Sheng Lin1,3,4,5,6,
  3. Chih-Jung Chang1,3,4,5,6,
  4. Tzu-Lung Lin1,
  5. Jan Martel3,5,
  6. Yun-Fei Ko5,7,8,
  7. David M Ojcius3,5,9,
  8. Chia-Chen Lu10,
  9. John D Young3,5,7,8,11,
  10. Hsin-Chih Lai1,3,4,5,6,12,13,14
  1. 1 Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Gueishan, Taiwan
  2. 2 Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Gueishan, Taiwan
  3. 3 Center for Molecular and Clinical Immunology, Chang Gung University, Gueishan, Taiwan
  4. 4 Microbiota Research Center, Chang Gung University, Gueishan, Taiwan
  5. 5 Chang Gung Immunology Consortium, Linkou Chang Gung Memorial Hospital, Gueishan, Taiwan
  6. 6 Research Center for Emerging Viral Infections, Chang Gung University, Gueishan, Taiwan
  7. 7 Chang Gung Biotechnology Corporation, Taipei, Taiwan
  8. 8 Biochemical Engineering Research Center, Ming Chi University of Technology, Taishan, Taiwan
  9. 9 Department of Biomedical Sciences, University of the Pacific, Arthur Dugoni School of Dentistry, San Francisco, California, USA
  10. 10 Department of Respiratory Therapy, Fu Jen Catholic University, Xinzhuang, Taiwan
  11. 11 Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, USA
  12. 12 Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Gueishan, Taiwan
  13. 13 Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Gueishan, Taiwan
  14. 14 Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Gueishan, Taiwan
  1. Correspondence to Dr John D Young, Center for Molecular and Clinical Immunology, Chang Gung University, Gueishan, Taoyuan 33302, Taiwan; jdyoung{at}mail.cgu.edu.tw and Dr Hsin-Chih Lai, Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Gueishan, Taoyuan 33302, Taiwan; hclai{at}mail.cgu.edu.tw

Abstract

Objective The medicinal fungus Ophiocordyceps sinensis and its anamorph Hirsutella sinensis have a long history of use in traditional Chinese medicine for their immunomodulatory properties. Alterations of the gut microbiota have been described in obesity and type 2 diabetes. We examined the possibility that H. sinensis mycelium (HSM) and isolated fractions containing polysaccharides may prevent diet-induced obesity and type 2 diabetes by modulating the composition of the gut microbiota.

Design High-fat diet (HFD)-fed mice were treated with HSM or fractions containing polysaccharides of different molecular weights. The effects of HSM and polysaccharides on the gut microbiota were assessed by horizontal faecal microbiota transplantation (FMT), antibiotic treatment and 16S rDNA-based microbiota analysis.

Results Fraction H1 containing high-molecular weight polysaccharides (>300 kDa) considerably reduced body weight gain (∼50% reduction) and metabolic disorders in HFD-fed mice. These effects were associated with increased expression of thermogenesis protein markers in adipose tissues, enhanced gut integrity, reduced intestinal and systemic inflammation and improved insulin sensitivity and lipid metabolism. Gut microbiota analysis revealed that H1 polysaccharides selectively promoted the growth of Parabacteroides goldsteinii, a commensal bacterium whose level was reduced in HFD-fed mice. FMT combined with antibiotic treatment showed that neomycin-sensitive gut bacteria negatively correlated with obesity traits and were required for H1’s anti-obesogenic effects. Notably, oral treatment of HFD-fed mice with live P. goldsteinii reduced obesity and was associated with increased adipose tissue thermogenesis, enhanced intestinal integrity and reduced levels of inflammation and insulin resistance.

Conclusions HSM polysaccharides and the gut bacterium P. goldsteinii represent novel prebiotics and probiotics that may be used to treat obesity and type 2 diabetes.

  • colonic microflora
  • obesity
  • diabetes mellitus
  • nutrition
  • prebiotic

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Footnotes

  • T-RW, C-SL and C-JC contributed equally.

  • Contributors T-RW, C-SL and C-JC conceived the project, contributed to experimental design, performed experiments, interpreted the results, prepared the figures and wrote the manuscript; T-LL performed experiments and interpreted the results; JDY and H-CL conceived and supervised the project, interpreted the results and wrote the manuscript; JM, DMO and C-CL interpreted the results and wrote the manuscript; Y-FK provided the HSM extract and polysaccharides fractions; all authors discussed the results and approved the manuscript.

  • Funding The authors’ work is supported by the Primordia Institute of New Sciences and Medicine; the Research Center for Emerging Viral Infections (Chang Gung University); the Featured Areas Research Center Program, which is part of the Higher Education Sprout Project of the Ministry of Education of Taiwan; by grants MOST105-2320-B-182-032-MY3, MOST105-2320-B-030-004, MOST103-2321-B-182-014-MY3 and MOST107-3017-F-182-001 from the Ministry of Science and Technology of Taiwan; and by grants BMRPA04, CMRPD1E0073, CMRPD1F0123, CORPD1F0011-3, QZRPD142 and QZRPD146 from Chang Gung Memorial Hospital.

  • Competing interests Y-FK is President of Chang Gung Biotechnology Corporation. JDY is Chairman of the Board of Chang Gung Biotechnology Corporation. The authors own patents related to the preparation and use of medicinal fungi and probiotics.

  • Patient consent Not required.

  • Ethics approval This study was approved by Chang Gung University’s Institutional Animal Care and Use Committee (Document No. CGU11-117). Experiments were performed in accordance with the guidelines.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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