Professor Zhaoxiang Bian
Associate Vice-President (Chinese Medicine Development) of HKBU
- (852) 3411 2905
Associate Vice-President (Chinese Medicine Development) of HKBU; Tsang Shiu Tim Endowed Chair of Chinese Medicine Clinical Studies; Director and Chair Professor of Clinical Division; Director, Hong Kong Chinese Medicine Clinical Study Centre; Associate Director, Institute of Creativity; Programme Director of Master of Science in Personal Health Management (Chinese Medicine) programme
|2nd Award||2018 International Award for Contribution to Chinese Medicine-achievement Award in Medical Science. World Federation of Chinese Medicine Society, 2018.|
|Golden Award||46th International Exhibition of Inventions Geneva. Geneva. 2018.|
|Science and Technology Award (1st Class)||China Association for Traditional Chinese Medicine, P. R. China, 2013|
|Research Award (2nd Class)||4th internal conference of integrated digestive disease, World Association of Chinese Medicine, 2013|
|Top Ten Research Papers||China Medicinal Plants Association, 2012|
|Long Service Award||Hong Kong Baptist University, 2011|
Early life stress disrupts intestinal homeostasis via NGF-TrkA signaling (Nature communications 2019; 10: 1745)
Early childhood is a critical period for development, and early life stress may increase the risk of gastrointestinal diseases including irritable bowel syndrome (IBS). In rodents, neonatal maternal separation (NMS) induces bowel dysfunctions that resemble IBS. However, the underlying mechanisms remain unclear. Here we show that NMS induces expansion of intestinal stem cells (ISCs) and their differentiation toward secretory lineages including enterochromaffin (EC) and Paneth cells, leading to EC hyperplasia, increased serotonin production, and visceral hyperalgesia. This is reversed by inhibition of nerve growth factor (NGF)-mediated tropomyosin receptor kinase A (TrkA) signalling, and treatment with NGF recapitulates the intestinal phenotype of NMS mice in vivo and in mouse intestinal organoids in vitro. Mechanistically, NGF transactivates Wnt/β-catenin signalling. NGF and serotonin are positively correlated in the sera of diarrhea-predominant IBS patients. Together, our findings provide mechanistic insights into early life stress-induced intestinal changes that may translate into treatments for gastrointestinal diseases.
Early-life stress induces enterochromaffin cell hyperplasia
- Figure 1. The increased density of serotonin-producing enterochroma-ffin cells in both small intestines and proximal colons from NMS mice. Blocking NGF signaling by NMAC13, a neutral-lizing antibody from TrkA, suppressed the enterochromaffin cell hyperplasia in NMS mice.
Early-life stress leads to expansion of the ISC compartment through NGF/TrkA signaling
- Figure 2. Colonic stem cells were labelled with EGFP (green) in the sections of proximal colons from both control and NMS Lgr5-EGFP+ mice treated with or without intraperitoneal injection of NGF and NMAC13. Meanwhile , the colonic sections were also co-immunostained with Sox9 and DAPI.
NGF/TrkA regulates ISC expansion through Wnt signaling
- Figure 3. Intestinal organoids treated with NGF are resistant to Wnt inhibition. Exogenous NGF rescues the depletion of colonic stem cells by Wnt inhibition.
The correlation between NGF and serotonin in IBS-D patients
- Figure 4. By means of enzyme-linked immunosorbent assay (ELISA), we found that both NGF and serotonin are markedly upregulated in the sera of IBS-D patients (a,b). Moreover, there was a significant positive correlation between serum NGF and serotonin (c), reinforcing the regulatory role for NGF in serotonin production in early-life stress-associated bowel disorders.
Ten Most Representative Publications
- Zhao L, Yang W, Huang F, Lu L, Lin C, Huang T, Ning Z, Zhai L, Zhong LLD, Lam W, Yang Z, Zhang X, Cheng C, Han L, Qiu Q, Shang X, Huang R, Xiao H, Ren Z, Chen D, Sun S, El-Nezami H, Lu A, Fang X*, Jia W*, Bian Z*. A Clostridia-rich microbiota enhances bile acid excretion in diarrhea-predominant irritable bowel syndrome. J Clin Invest. 2020 Jan 2;130(1):438-450. doi: 10.1172/JCI130976.
- Wong HLX, Qin H, Tsang SW, Zuo X, Che S, Chow CFW, Li X. Xiao HT, Zhao L, Huang T, Lin CY, Kwan HY, Yang T, Longo FM, Lyu A, Bian Z (2019) Early life stress disrupts intestinal homeostasis via NGF-TrkA signaling. Nature Communications 10(1):1745. doi: 10.1038/s41467-019-09744-3.
- Chow CFW, Che S, Qin HY, Kwan HY, Bian ZX*, Wong HLX*. From psychology to physicality: How nerve growth factor transduces early life stress into gastrointestinal motility disorders later in life. Cell Cycle. 2019 Aug;18(16):1824-1829. doi: 10.1080/15384101.2019.1637203.
- Qin HY, Zang KH, Zuo X, Wu XA, Bian ZX. (2019) Quercetin Attenuates Visceral Hypersensitivity and 5-Hydroxytryptamine Availability in Postinflammatory Irritable Bowel Syndrome Rats: Role of Enterochromaffin Cells in the Colon. J Med Food. 2019 Mar 28.
- Zhao L, Huang Y, Lu L, Yang W, Huang T, Lin Z, Lin CY, Kwan HY, Wong HLX, Chen Y, Sun S, Xie X, Fang X, Yang H, Wang J, Zhu L, Bian Z (2018) Saturated long-chain fatty acid-producing bacteria contributes to enhanced colonic motility in rats. Microbiome 2018;6(1):107.https://doi.org/10.1186/s40168-018-0492-6.
- Chen GQ, Gong RH, Yang DJ, Zhang G, Lu AP, Yan SC, Lin SH*, Bian ZX*. Halofuginone dually regulates autophagic flux through nutrient-sensing pathways in colorectal cancer. Cell Death Dis. 2017 May 11;8(5):e2789.doi: 10.1038/cddis.2017.203.
- Chung EK, Zhang XJ, Li Z, Zhang HQ, Xu HX, Bian ZX. Neonatal maternal separation enhances central sensitivity to noxious colorectal distention in rat. Brain Res., 2007, 1153: 68-77. 2. doi: 10.1016/j.brainres.2007.03.047
- Bian ZX, WU TX, Liu L, Miao JX, Wong HF, Song L, Sung JJY. Effectiveness of the Chinese herbal formula TongXieYaoFang for irritable bowel syndrome: a systematic review. J Altern Complement Med., 2006, 12, 401- 407. 3. https://doi.org/10.1089/acm.2006.12.401.
- Tian XY, Bian ZX, Hu XG, Zhang XJ, Liu L, Zhang HQ. Electro-acupuncture attenuates stress-induced defecation in rats with chronic visceral hypersensitivity via serotonergic pathway. Brain Res, 2006, 1088:101-8. 4. doi: 10.1016/j.brainres.2006.03.014
- Bian ZX. Stratification by sex and subgroup is necessary for RCT on IBS. Gut, 2006, 55: 743-4. 5.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1856123/