Lactobacillus johnsonii Attenuates Citrobacter rodentium-Induced Colitis by Regulating Inflammatory Responses and Endoplasmic Reticulum Stress in Mice.

BACKGROUND Probiotics are beneficial in intestinal disorders. However, the benefits of Lactobacillus johnsonii in experimental colitis remain unknown. OBJECTIVES This study aimed to investigate the benefits of L. johnsonii against Citrobacter rodentium-induced colitis. METHODS Thirty-six 5-wk-old female C57BL/6J mice were randomly assigned to 3 groups (n = 12): control (Ctrl) group, Citrobacter rodentium treatment (CR) group (2 × 109 CFU C. rodentium), and Lactobacillus johnsonii and Citrobacter rodentium cotreatment (LJ + CR) group (109 CFU L. johnsonii with C. rodentium). Colon length, mucosal thickness, proinflammatory cytokine genes, and endoplasmic reticulum stress were tested. RESULTS The CR group had greater spleen weight, mucosal thickness, and Ki67+ cells (0.4-4.7 times), and a 23.8% shorter colon length than the Ctrl group, which in the LJ + CR group were 22.4%-77.6% lower and 30% greater than in the CR group, respectively. Relative to the Ctrl group, serum proinflammatory cytokines and immune cell infiltration were greater by 0.3-1.6 times and 6.2-8.8 times in the CR group, respectively; relative to the CR group, these were 19.9%-61.9% and 69.5%-84.2% lower in the LJ + CR group, respectively. The mRNA levels of lysozyme (Lyz) and regenerating islet-derived protein III were 22.7%-36.5% lower and 1.5-2.7 times greater in the CR group than in the Ctrl group, respectively, whereas they were 22.2%-25.7% greater and 57.2%-76.9% lower in the LJ + CR group than in the CR group, respectively. Cell apoptosis was 11.9 times greater in the CR group than in the Ctrl group, and 87.4% lower in the LJ + CR group than in the CR group. Consistently, the protein abundances of C/EBP homologous protein (CHOP), cleaved caspase 1 and 3, activating transcription factor 6α (ATF6A), and phospho-inositol-requiring enzyme 1α (P-IRE1A) were 0.3-2.1 times greater in the CR group and 31.1%-60.4% lower in the LJ + CR group. All these indexes did not differ between the Ctrl and LJ + CR groups, except for CD8+ T lymphocytes and CD11b+ and F4/80+ macrophages (1-1.5 times greater in LJ + CR) and mRNA concentration of Lyz2 (20.1% lower in LJ + CR). CONCLUSIONS L. johnsonii supplementation is a promising nutritional strategy for preventing C. rodentium-induced colitis in mice.

[1]  A. Kaser,et al.  Activating Transcription Factor 6 Mediates Inflammatory Signals in Intestinal Epithelial Cells Upon Endoplasmic Reticulum Stress. , 2020, Gastroenterology.

[2]  E. Elinav,et al.  Interaction between microbiota and immunity in health and disease , 2020, Cell Research.

[3]  Zhenlong Wu,et al.  Glycine Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Regulating NLRP3 Inflammasome and NRF2 Signaling , 2020, Nutrients.

[4]  Yaohong Zhu,et al.  Anti-inflammatory effects of Lactobacillus johnsonii L531 in a pig model of Salmonella Infantis infection involves modulation of CCR6+ T cell responses and ER stress , 2020, Veterinary Research.

[5]  Lajia Zha,et al.  Alteration of Gut Microbiota in Inflammatory Bowel Disease (IBD): Cause or Consequence? IBD Treatment Targeting the Gut Microbiome , 2019, Pathogens.

[6]  Louis J. Cohen,et al.  Genetic Factors and the Intestinal Microbiome Guide Development of Microbe-Based Therapies for Inflammatory Bowel Diseases. , 2019, Gastroenterology.

[7]  D. Zeng,et al.  Probiotic Lactobacillus johnsonii BS15 Promotes Growth Performance, Intestinal Immunity, and Gut Microbiota in Piglets , 2019, Probiotics and Antimicrobial Proteins.

[8]  C. Ding,et al.  The C/EBP Homologous Protein (CHOP) Transcription Factor Functions in Endoplasmic Reticulum Stress-Induced Apoptosis and Microbial Infection , 2019, Front. Immunol..

[9]  Guoyao Wu,et al.  Glycine supplementation to breast-fed piglets attenuates post-weaning jejunal epithelial apoptosis: a functional role of CHOP signaling , 2018, Amino Acids.

[10]  Laurel A. Doherty,et al.  Effects of Psychological, Environmental and Physical Stressors on the Gut Microbiota , 2018, Front. Microbiol..

[11]  D. H. Kim,et al.  Lactobacillus acidophilus suppresses intestinal inflammation by inhibiting endoplasmic reticulum stress , 2018, Journal of gastroenterology and hepatology.

[12]  S. Cao,et al.  Cellular Stress Responses and Gut Microbiota in Inflammatory Bowel Disease , 2018, Gastroenterology research and practice.

[13]  A. Ananthakrishnan,et al.  The role of diet in the aetiopathogenesis of inflammatory bowel disease , 2018, Nature Reviews Gastroenterology & Hepatology.

[14]  Wei Chen,et al.  Lactobacillus plantarum CCFM10 alleviating oxidative stress and restoring the gut microbiota in d-galactose-induced aging mice. , 2018, Food & function.

[15]  Xiaodan Qing,et al.  Probiotic Lactobacillus johnsonii BS15 Improves Blood Parameters Related to Immunity in Broilers Experimentally Infected with Subclinical Necrotic Enteritis , 2018, Front. Microbiol..

[16]  Guoyao Wu,et al.  Intestinal Epithelial Cell Endoplasmic Reticulum Stress and Inflammatory Bowel Disease Pathogenesis: An Update Review , 2017, Front. Immunol..

[17]  Jinhua Zhang,et al.  S100A4 contributes to colitis development by increasing the adherence of Citrobacter rodentium in intestinal epithelial cells , 2017, Scientific Reports.

[18]  Seockmo Ku,et al.  The Efficacy of Bifidobacterium longum BORI and Lactobacillus acidophilus AD031 Probiotic Treatment in Infants with Rotavirus Infection , 2017, Nutrients.

[19]  J. Badia,et al.  Intestinal Anti-inflammatory Effects of Outer Membrane Vesicles from Escherichia coli Nissle 1917 in DSS-Experimental Colitis in Mice , 2017, Front. Microbiol..

[20]  Dong-Hyun Kim,et al.  Lactobacillus johnsonii CJLJ103 attenuates colitis and memory impairment in mice by inhibiting gut microbiota lipopolysaccharide production and NF-κB activation , 2017 .

[21]  K. Stingl,et al.  Lactobacillus johnsonii ameliorates intestinal, extra-intestinal and systemic pro-inflammatory immune responses following murine Campylobacter jejuni infection , 2017, Scientific Reports.

[22]  I. Thiele,et al.  Gut microbiota functions: metabolism of nutrients and other food components , 2017, European Journal of Nutrition.

[23]  T. Hand.  The Role of the Microbiota in Shaping Infectious Immunity. , 2016, Trends in immunology.

[24]  D. Schwarz,et al.  The endoplasmic reticulum: structure, function and response to cellular signaling , 2015, Cellular and Molecular Life Sciences.

[25]  E. Chang,et al.  IBD and the Gut Microbiota—from Bench to Personalized Medicine , 2015, Current Gastroenterology Reports.

[26]  K. Luo,et al.  Endoplasmic Reticulum Stress in Intestinal Epithelial Cell Function and Inflammatory Bowel Disease , 2015, Gastroenterology research and practice.

[27]  David M Richards,et al.  Systematic review of randomized controlled trials of probiotics, prebiotics, and synbiotics in inflammatory bowel disease , 2014, Clinical and experimental gastroenterology.

[28]  Angela C. Poole,et al.  Human Genetics Shape the Gut Microbiome , 2014, Cell.

[29]  B. Finlay,et al.  Citrobacter rodentium: infection, inflammation and the microbiota , 2014, Nature Reviews Microbiology.

[30]  Glenn R. Gibson,et al.  The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic , 2014 .

[31]  Ali A. Faruqi,et al.  House dust exposure mediates gut microbiome Lactobacillus enrichment and airway immune defense against allergens and virus infection , 2013, Proceedings of the National Academy of Sciences.

[32]  N. Barker.  Adult intestinal stem cells: critical drivers of epithelial homeostasis and regeneration , 2013, Nature Reviews Molecular Cell Biology.

[33]  T. Brusko,et al.  Influence of host immunoregulatory genes, ER stress and gut microbiota on the shared pathogenesis of inflammatory bowel disease and Type 1 diabetes. , 2013, Immunotherapy.

[34]  Bing Xia,et al.  Increased Proportions of Bifidobacterium and the Lactobacillus Group and Loss of Butyrate-Producing Bacteria in Inflammatory Bowel Disease , 2013, Journal of Clinical Microbiology.

[35]  Paul M. Ruegger,et al.  Intestinal bacteria modify lymphoma incidence and latency by affecting systemic inflammatory state, oxidative stress, and leukocyte genotoxicity. , 2013, Cancer research.

[36]  R. Kaufman,et al.  The unfolded protein response and chemical chaperones reduce protein misfolding and colitis in mice. , 2013, Gastroenterology.

[37]  J. Nicholson,et al.  Gut microbiota composition and activity in relation to host metabolic phenotype and disease risk. , 2012, Cell metabolism.

[38]  Christine E. Becker,et al.  TRIF Licenses Caspase-11-Dependent NLRP3 Inflammasome Activation by Gram-Negative Bacteria , 2012, Cell.

[39]  M. Neuman,et al.  Inflammatory bowel disease: role of diet, microbiota, life style. , 2012, Translational research : the journal of laboratory and clinical medicine.

[40]  M. Gareau,et al.  Probiotics are effective for the prevention and treatment of Citrobacter rodentium-induced colitis in mice. , 2012, The Journal of infectious diseases.

[41]  M. Neurath,et al.  Apoptosis, necrosis and necroptosis: cell death regulation in the intestinal epithelium , 2012, Gut.

[42]  H. Nishitoh.  CHOP is a multifunctional transcription factor in the ER stress response. , 2012, Journal of biochemistry.

[43]  Jinfeng Liu,et al.  Non-canonical inflammasome activation targets caspase-11 , 2011, Nature.

[44]  Philippe Seksik,et al.  Epidemiology and natural history of inflammatory bowel diseases. , 2011, Gastroenterology.

[45]  F. Fava,et al.  Intestinal microbiota in inflammatory bowel disease: friend of foe? , 2011, World journal of gastroenterology.

[46]  S. Park,et al.  Endoplasmic Reticulum Stress-activated C/EBP Homologous Protein Enhances Nuclear Factor-κB Signals via Repression of Peroxisome Proliferator-activated Receptor γ* , 2010, The Journal of Biological Chemistry.

[47]  A. Kaser,et al.  Endoplasmic reticulum stress: implications for inflammatory bowel disease pathogenesis , 2010, Current opinion in gastroenterology.

[48]  P. Bork,et al.  A human gut microbial gene catalogue established by metagenomic sequencing , 2010, Nature.

[49]  T. Gotoh,et al.  Positive role of CCAAT/enhancer-binding protein homologous protein, a transcription factor involved in the endoplasmic reticulum stress response in the development of colitis. , 2009, The American journal of pathology.

[50]  J. Walter.  Ecological Role of Lactobacilli in the Gastrointestinal Tract: Implications for Fundamental and Biomedical Research , 2008, Applied and Environmental Microbiology.

[51]  O. Dewit,et al.  Multicenter randomized‐controlled clinical trial of probiotics (Lactobacillus johnsonii, LA1) on early endoscopic recurrence of Crohn's disease after ileo‐caecal resection , 2007 .

[52]  Q. Ouyang,et al.  Probiotics and inflammatory bowel diseases , 2006, Postgraduate Medical Journal.

[53]  J. Mary,et al.  Ineffectiveness of Lactobacillus johnsonii LA1 for prophylaxis of postoperative recurrence in Crohn’s disease: a randomised, double blind, placebo controlled GETAID trial , 2005, Gut.

[54]  J. Furet,et al.  Molecular quantification of lactic acid bacteria in fermented milk products using real-time quantitative PCR. , 2004, International journal of food microbiology.

[55]  S. Oyadomari,et al.  Roles of CHOP/GADD153 in endoplasmic reticulum stress , 2004, Cell Death and Differentiation.

[56]  A. Pfeifer,et al.  Non-pathogenic bacteria elicit a differential cytokine response by intestinal epithelial cell/leucocyte co-cultures , 2000, Gut.

[57]  G. Dougan,et al.  Citrobacter rodentium Infection in Mice Elicits a Mucosal Th1 Cytokine Response and Lesions Similar to Those in Murine Inflammatory Bowel Disease , 1999, Infection and Immunity.

[58]  D. Brassart,et al.  Lactobacillus acidophilus LA 1 binds to cultured human intestinal cell lines and inhibits cell attachment and cell invasion by enterovirulent bacteria. , 1994, Gut.

[59]  R. Okamoto,et al.  Role of epithelial cells in the pathogenesis and treatment of inflammatory bowel disease , 2015, Journal of Gastroenterology.

[60]  Guoyao Wu,et al.  Glutamine enhances tight junction protein expression and modulates corticotropin-releasing factor signaling in the jejunum of weanling piglets. , 2015, The Journal of nutrition.

[61]  Aditya P. Dandekar,et al.  Cross talk between ER stress, oxidative stress, and inflammation in health and disease. , 2015, Methods in molecular biology.

[62]  A. Nusrat,et al.  Gastrointestinal , Hepatobiliary , and Pancreatic Pathology Probiotic Bacteria Induce Maturation of Intestinal Claudin 3 Expression and Barrier Function , 2012 .

[63]  Darrell B. O'Quinn,et al.  Emergence of the Th17 pathway and its role in host defense. , 2008, Advances in immunology.