Total Flavone of Abelmoschus manihot Ameliorates Stress-Induced Microbial Alterations Drive Intestinal Barrier Injury in DSS Colitis

Purpose Total flavone of Abelmoschus manihot (TFA), the effective constituents extracted from Flos Abelmoschus Manihot, has been reported to inhibit inflammation. However, the effect of TFA on ulcerative colitis (UC) progression in patients with depression is unknown. The purpose of our research was to explore the anti-UC effects of TFA in the context of depression in mice with UC by regulating the gut microbiota to drive the intestinal barrier. Methods In this study, chronic stress (CS) and dextran sodium sulfate (DSS) were used to induce depression and UC, respectively, in C57BL/6J mice. Fecal microbiota transplantation (FMT) was used to evaluate how treating mice modeling UC and depression with TFA effected their gut microbiota. Results Our results showed that TFA effectively improved UC aggravated by CS. In addition, TFA treatment improved the depression-like phenotype, the disturbed gut microbiota, and the intestinal barrier function in CS mice. It is worth noting that FMT from the CS mice to the receptor group further aggravated the damage of the intestinal barrier and the disturbance of the gut microbiota in the recipient DSS mice, thus further aggravating UC, however, treatment of the intervention of TFA in the CS fecal microbiota transplant with TFA also played its therapeutic outcome. Conclusion Taken together, our results show that CS disrupts the gut microbiota, triggers intestinal barrier injury and aggravates DSS colitis, while TFA is a promising drug for the treatment of UC in patients with depression.

[1]  M. Hotopf,et al.  Depression in individuals who subsequently develop inflammatory bowel disease: a population-based nested case–control study , 2020, Gut.

[2]  T. Mendes,et al.  Use of the synbiotic VSL#3 and yacon-based concentrate attenuates intestinal damage and reduces the abundance of Candidatus Saccharimonas in a colitis-associated carcinogenesis model. , 2020, Food research international.

[3]  Ziren Su,et al.  Oxyberberine, a novel gut microbiota-mediated metabolite of berberine, possesses superior anti-colitis effect: impact on intestinal epithelial barrier, gut microbiota profile and TLR4-MyD88-NF-κB pathway. , 2019, Pharmacological research.

[4]  Jie Ren,et al.  Phloretin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice by regulating the gut microbiota. , 2019, Pharmacological research.

[5]  Jian-Guo Jiang,et al.  Antidepressant active ingredients from herbs and nutraceuticals used in TCM: pharmacological mechanisms and prospects for drug discovery. , 2019, Pharmacological research.

[6]  Chao Guo,et al.  Infliximab clinically treating ulcerative colitis: A systematic review and meta-analysis. , 2019, Pharmacological research.

[7]  Jianming Guo,et al.  Flos Abelmoschus manihot extract attenuates DSS-induced colitis by regulating gut microbiota and Th17/Treg balance. , 2019, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[8]  Dianliang Zhang,et al.  Effects of regulating gut microbiota on the serotonin metabolism in the chronic unpredictable mild stress rat model , 2019, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[9]  Jin-Yong Zhou,et al.  Total flavone of Abelmoschus manihot ameliorates Crohn's disease by regulating the NF‑κB and MAPK signaling pathways. , 2019, International journal of molecular medicine.

[10]  M. Camilleri.  Leaky gut: mechanisms, measurement and clinical implications in humans , 2019, Gut.

[11]  Yugen Chen,et al.  Huangkui Lianchang Decoction Ameliorates DSS-Induced Ulcerative Colitis in Mice by Inhibiting the NF-kappaB Signaling Pathway , 2019, Evidence-based complementary and alternative medicine : eCAM.

[12]  J. Mann,et al.  Systematic Review of Gut Microbiota and Major Depression , 2019, Front. Psychiatry.

[13]  G. Shearer,et al.  Microbiota fermentation-NLRP3 axis shapes the impact of dietary fibres on intestinal inflammation , 2019, Gut.

[14]  Yan Cai,et al.  Gut microbiota dysbiosis worsens the severity of acute pancreatitis in patients and mice , 2018, Journal of Gastroenterology.

[15]  P. Barral,et al.  Quantitative Polymerase Chain Reaction-based Analyses of Murine Intestinal Microbiota After Oral Antibiotic Treatment. , 2018, Journal of visualized experiments : JoVE.

[16]  Jianming Xu,et al.  SRC-3 protects intestine from DSS-induced colitis by inhibiting inflammation and promoting goblet cell differentiation through enhancement of KLF4 expression , 2018, International journal of biological sciences.

[17]  G. Kaplan,et al.  Depression increases the risk of inflammatory bowel disease, which may be mitigated by the use of antidepressants in the treatment of depression , 2018, Gut.

[18]  Hong-jin Chen,et al.  Total flavone of Abelmoschus manihot suppresses epithelial-mesenchymal transition via interfering transforming growth factor-β1 signaling in Crohn’s disease intestinal fibrosis , 2018, World journal of gastroenterology.

[19]  A. Hartikainen,et al.  The Potential of Gut Commensals in Reinforcing Intestinal Barrier Function and Alleviating Inflammation , 2018, Nutrients.

[20]  A. Neish,et al.  Role of gut microbiota in intestinal wound healing and barrier function , 2018, Tissue barriers.

[21]  Zhe Wu,et al.  5-Aminosalicylic Acid Alters the Gut Bacterial Microbiota in Patients With Ulcerative Colitis , 2018, Front. Microbiol..

[22]  Jia-Rong Wu,et al.  Current Rapid-Onset Antidepressants and Related Animal Models. , 2018, Current pharmaceutical design.

[23]  Zhi Liu,et al.  Antidepressant Effects of the Ginsenoside Metabolite Compound K, Assessed by Behavioral Despair Test and Chronic Unpredictable Mild Stress Model , 2018, Neurochemical Research.

[24]  Tao Yang,et al.  Lactobacillus frumenti Facilitates Intestinal Epithelial Barrier Function Maintenance in Early-Weaned Piglets , 2018, Front. Microbiol..

[25]  A. Ford,et al.  Bi-directionality of Brain-Gut Interactions in Patients With Inflammatory Bowel Disease. , 2018, Gastroenterology.

[26]  L. Birnbaumer,et al.  Chronic stress promotes colitis by disturbing the gut microbiota and triggering immune system response , 2018, Proceedings of the National Academy of Sciences.

[27]  Christopher F. Martin,et al.  Depression Is Associated With More Aggressive Inflammatory Bowel Disease , 2018, The American Journal of Gastroenterology.

[28]  C. Pepine,et al.  Increased human intestinal barrier permeability plasma biomarkers zonulin and FABP2 correlated with plasma LPS and altered gut microbiome in anxiety or depression , 2017, Gut.

[29]  Xi Sun,et al.  rSj16 Protects against DSS-Induced Colitis by Inhibiting the PPAR-α Signaling Pathway , 2017, Theranostics.

[30]  Na Li,et al.  Interaction between the gut microbiome and mucosal immune system , 2017, Military Medical Research.

[31]  A. Harkin,et al.  Gut–brain actions underlying comorbid anxiety and depression associated with inflammatory bowel disease , 2017, Acta Neuropsychiatrica.

[32]  W. D. de Vos,et al.  Pili-like proteins of Akkermansia muciniphila modulate host immune responses and gut barrier function , 2017, PloS one.

[33]  Lisa M Bramer,et al.  Dynamics of the human gut microbiome in Inflammatory Bowel Disease , 2017, Nature Microbiology.

[34]  T. Dinan,et al.  Transferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the rat. , 2016, Journal of psychiatric research.

[35]  T. Dinan,et al.  Gut microbiota, obesity and diabetes , 2016, Postgraduate Medical Journal.

[36]  C. Sohn,et al.  Factors Associated with Anxiety and Depression in Korean Patients with Inactive Inflammatory Bowel Disease , 2015, Gut and liver.

[37]  H. Tajiri,et al.  Psychological stress exacerbates NSAID-induced small bowel injury by inducing changes in intestinal microbiota and permeability via glucocorticoid receptor signaling , 2016, Journal of Gastroenterology.

[38]  V. Shcherbakova,et al.  Alistipes inops sp. nov. and Coprobacter secundus sp. nov., isolated from human faeces. , 2015, International journal of systematic and evolutionary microbiology.

[39]  Bing Ruan,et al.  Altered fecal microbiota composition in patients with major depressive disorder , 2015, Brain, Behavior, and Immunity.

[40]  F. Bäckhed,et al.  The composition of the gut microbiota shapes the colon mucus barrier , 2014, EMBO reports.

[41]  M. Johansson.  Mucus Layers in Inflammatory Bowel Disease , 2014, Inflammatory bowel diseases.

[42]  Markus F. Neurath,et al.  Cytokines in inflammatory bowel disease , 2014, Nature Reviews Immunology.

[43]  H. Sann,et al.  Efficacy of drugs used in the treatment of IBD and combinations thereof in acute DSS-induced colitis in mice. , 2013, Life sciences.

[44]  Takuya Suzuki.  Regulation of intestinal epithelial permeability by tight junctions , 2012, Cellular and Molecular Life Sciences.

[45]  Ai-Hua Zhang,et al.  Pretreatment with the total flavone glycosides of Flos Abelmoschus manihot and hyperoside prevents glomerular podocyte apoptosis in streptozotocin-induced diabetic nephropathy. , 2012, Journal of medicinal food.

[46]  M. Sprangers,et al.  Do Inflammatory Bowel Disease patients with anxiety and depressive symptoms receive the care they need? , 2012, Journal of Crohn's & colitis.

[47]  Zhaohui J. Cai,et al.  Pretreatment data is highly predictive of liver chemistry signals in clinical trials , 2012, Drug design, development and therapy.

[48]  P. Bhutada,et al.  Reversal by quercetin of corticotrophin releasing factor induced anxiety- and depression-like effect in mice , 2010, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[49]  Y. S. Kim,et al.  Intestinal Goblet Cells and Mucins in Health and Disease: Recent Insights and Progress , 2010, Current gastroenterology reports.

[50]  C. Bernstein,et al.  Depression and anxiety in inflammatory bowel disease: A review of comorbidity and management , 2009, Inflammatory bowel diseases.

[51]  Lan-lan Zhou,et al.  Protective Effect of Total Flavones of Abelmoschus manihot L. Medic Against Poststroke Depression Injury in Mice and Its Action Mechanism , 2009, Anatomical record.

[52]  T. Okanoue,et al.  Involvement of IL-17A in the pathogenesis of DSS-induced colitis in mice. , 2008, Biochemical and biophysical research communications.

[53]  Hannah M. Wexler,et al.  Bacteroides: the Good, the Bad, and the Nitty-Gritty , 2007, Clinical Microbiology Reviews.

[54]  K. James.  Drug design , 1992, Nature.