Gut commensal Parabacteroides goldsteinii plays a predominant role in the anti-obesity effects of polysaccharides isolated from Hirsutella sinensis
Authors: Chih-Jung Chang
Yun-Fei Ko
David M Ojcius
Chia-Chen Lu
Jan Martel
Tsung-Ru Wu
Tzu-Lung Lin
John D Young
Chuan-Sheng Lin
Hsin-Chih Lai
Journal: Gut (2019)
Discipline: CLINICAL MEDICINE
Keywords: colonic microflora; diabetes mellitus; nutrition; obesity; prebiotic.
Affiliations: Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Gueishan, Taiwan., Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Gueishan, Taiwan., Center for Molecular and Clinical Immunology, Chang Gung University, Gueishan, Taiwan., Microbiota Research Center, Chang Gung University, Gueishan, Taiwan., Chang Gung Immunology Consortium, Linkou Chang Gung Memorial Hospital, Gueishan, Taiwan., Research Center for Emerging Viral Infections, Chang Gung University, Gueishan, Taiwan., Chang Gung Biotechnology Corporation, Taipei, Taiwan., Biochemical Engineering Research Center, Ming Chi University of Technology, Taishan, Taiwan., Department of Biomedical Sciences, University of the Pacific, Arthur Dugoni School of Dentistry, San Francisco, California, USA., Department of Respiratory Therapy, Fu Jen Catholic University, Xinzhuang, Taiwan., Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, USA., Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Gueishan, Taiwan., Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Gueishan, Taiwan., Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Gueishan, Taiwan.

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 (&gt;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. 

Retracted: No

PubPeer comments:
 This paper shows a medium amount contamination, which does not seem to invalidate the main results. Plot #4 shows Delftia and Sphingomonas, which are usual contaminants, probably also Pseudomonas, and clearly Shewanella algae, but the rest of the data seems to be otherwise normal. Plot #7 shows more contamination, with plant associated bacteria (Bradyrhizobium japonicum, Stenotrophomonas) or environmental ones (Lysinibacillus, Solibacterium). Some of these genera show up as statistically significant in samples, where the microbiota has been reduced with antibiotics, allowing these contaminations to be visible more prominently. No negative control seems to have been included to detect this. ,