The Relationship Between Gut Microbiota and Inflammatory Diseases: The Role of Macrophages.
Wang Ji,Chen Wei-Dong,Wang Yan-Dong
Frontiers in microbiology
Gut microbiota, an integral part of the human body, comprise bacteria, fungi, archaea, and protozoa. There is consensus that the disruption of the gut microbiota (termed "gut dysbiosis") is influenced by host genetics, diet, antibiotics, and inflammation, and it is closely linked to the pathogenesis of inflammatory diseases, such as obesity and inflammatory bowel disease (IBD). Macrophages are the key players in the maintenance of tissue homeostasis by eliminating invading pathogens and exhibit extreme plasticity of their phenotypes, such as M1 or M2, which have been demonstrated to exert pro- and anti-inflammatory functions. Microbiota-derived metabolites, short-chain fatty acids (SCFAs) and Gram-negative bacterial lipopolysaccharides (LPS), exert anti-inflammatory or pro-inflammatory effects by acting on macrophages. Understanding the role of macrophages in gut microbiota-inflammation interactions might provide us a novel method for preventing and treating inflammatory diseases. In this review, we summarize the recent research on the relationship between gut microbiota and inflammation and discuss the important role of macrophages in this context.
Green tea polyphenols decrease weight gain, ameliorate alteration of gut microbiota, and mitigate intestinal inflammation in canines with high-fat-diet-induced obesity.
Li Yu,Rahman Sajid Ur,Huang Yingying,Zhang Yafei,Ming Pengfei,Zhu Lei,Chu Xiaoyan,Li Jinchun,Feng Shibin,Wang Xichun,Wu Jinjie
The Journal of nutritional biochemistry
Green tea polyphenols (GTPs) exhibit beneficial effects towards obesity and intestinal inflammation; however, the mechanisms and association with gut microbiota are unclear. We examined the role of the gut microbiota of GTPs treatment for obesity and inflammation. Canines were fed either a normal diet or high-fat diet with low (0.48% g/kg), medium (0.96% g/kg), or high (1.92% g/kg), doses of GTPs for 18 weeks. GTPs decreased the relative abundance of Bacteroidetes and Fusobacteria and increased the relative abundance of Firmicutes as revealed by 16S rRNA gene sequencing analysis. The relative proportion of Acidaminococcus, Anaerobiospirillum, Anaerovibrio, Bacteroides, Blautia, Catenibactetium, Citrobacter, Clostridium, Collinsella, and Escherichia were significantly associated with GTPs-induced weight loss. GTPs significantly (P<.01) decreased expression levels of inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and inhibited induction of the TLR4 signaling pathway compared with high-fat diet. We show that the therapeutic effects of GTPs correspond with changes in gut microbiota and intestinal inflammation, which may be related to the anti-inflammatory and anti-obesity mechanisms of GTPs.
A purified membrane protein from or the pasteurised bacterium blunts colitis associated tumourigenesis by modulation of CD8 T cells in mice.
Wang Lijuan,Tang Lei,Feng Yiming,Zhao Suying,Han Mei,Zhang Chuan,Yuan Gehui,Zhu Jun,Cao Shuyuan,Wu Qian,Li Lei,Zhang Zhan
OBJECTIVE:Gut microbiota have been linked to inflammatory bowel disease (IBD) and colorectal cancer (CRC). () is a gram-negative anaerobic bacterium that is selectively decreased in the faecal microbiota of patients with IBD, but its causative role and molecular mechanism in blunting colitis-associated colorectal cancer (CAC) remain inconclusive. This study investigates how engages the immune response in CAC. DESIGN:Mice were given dextran sulfate sodium to induce colitis, followed by azoxymethane to establish CAC with or without pasteurised or a specific outer membrane protein (Amuc_1100) treatment. Faeces from mice and patients with IBD or CRC were collected for 16S rRNA sequencing. The effects of or Amuc_1100 on the immune response in acute colitis and CAC were investigated. RESULTS: was significantly reduced in patients with IBD and mice with colitis or CAC. or Amuc_1100 could improve colitis, with a reduction in infiltrating macrophages and CD8 cytotoxic T lymphocytes (CTLs) in the colon. Their treatment also decreased CD16/32 macrophages in the spleen and mesenteric lymph nodes (MLN) of colitis mice. Amuc_1100 elevated PD-1 CTLs in the spleen. Moreover, and Amuc_1100 blunted tumourigenesis by expanding CTLs in the colon and MLN. Remarkably, they activated CTLs in the MLN, as indicated by TNF-α induction and PD-1downregulation. Amuc_1100 could stimulate and activate CTLs from splenocytes in CT26 cell conditioned medium. CONCLUSIONS:These data indicate that pasteurised or Amuc_1100 can blunt colitis and CAC through the modulation of CTLs.
Lycopene Ameliorates Experimental Colitis in Rats via Reducing Apoptosis and Oxidative Stress.
Gul Baykalir Burcu,Aksit Dilek,Dogru Mustafa Selim,Hanım Yay Arzu,Aksit Hasan,Seyrek Kamil,Attesahin Ahmet
International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition
Inflammatory bowel disease (IBD) is an inflammatory disorder involving colitis. Lycopene is a naturally occurring carotenoid that has attracted considerable attention as a potential chemopreventive agent. The impact of lycopene on colitis is currently unknown. The aim of this study was to investigate the protective effects of lycopene in a rat model of colitis induced by acetic acid. The animals were randomly divided into the following five groups: the control group, colitis group, colitis + sulfasalazine group as a positive control group, colitis + lycopene and lycopene groups. Colonic mucosal injury was assessed by biochemical and histopathological examinations. Malondialdehyde (MDA), superoxide dismutase (SOD) activity, total antioxidant status (TAS), ceruloplasmin (CPN), total sialic acid and iron (Fe) levels were evaluated in blood samples. MDA, SOD, TAS and DNA fragmentation levels were also measured in colon tissues. MDA (p < 0.05), total sialic acid (p < 0.05) and DNA fragmentation levels (p < 0.01) were significantly higher, and the activity of the antioxidant enzyme were lower in the colitis group than in the control group. Treatments with lycopene in the colitis decreased MDA, total sialic acid and DNA fragmentation levels, while SOD activity (p < 0.05), TAS (in colon p < 0.05; in serum p < 0.01), CPN (p < 0.05) and Fe levels (p < 0.05) were significantly increased. The histopathological evaluation also confirmed the foregoing findings. Treatment with lycopene ameliorated the biochemical and pathological alterations caused by colitis. The results obtained in this study indicate that lycopene may exert protective effects in experimental colitis and might, therefore, be useful for treatment of IBD.
Lycopene Alleviates DSS-Induced Colitis and Behavioral Disorders via Mediating Microbes-Gut-Brain Axis Balance.
Zhao Beita,Wu Jianbin,Li Jinghao,Bai Yue,Luo Yong,Ji Bing,Xia Bing,Liu Zhigang,Tan Xintong,Lv Jinyin,Liu Xuebo
Journal of agricultural and food chemistry
Gut microbes play significant roles in colitis development. The current study was aimed to uncover the preventive effects of lycopene (LYC), a functional carotenoid component, on colitis and the accompanied behavior disorders. The current study demonstrated that LYC treatment (50 mg/kg body weight/day) for 40 days prevented the dextran sulfate sodium (DSS)-induced gut barrier damages and inflammatory responses in male mice. LYC improved DSS-induced depression and anxiety-like behavioral disorders by suppressing neuroinflammation and prevented synaptic ultrastructure damages by upregulating the expressions of neurotrophic factor and postsynaptic-density protein. Moreover, LYC reshaped the gut microbiome in colitis mice by decreasing the relative abundance of proteobacteria and increasing the relative abundance and . LYC also elevated the generation of short-chain fatty acids and inhibited the permeability of lipopolysaccharide in colitis mice. In conclusion, LYC ameliorate DSS-induced colitis and behavioral disorders via mediating microbes-gut-brain axis balance.
Melatonin ameliorates TNBS-induced colitis in rats through the melatonin receptors: involvement of TLR4/MyD88/NF-κB signalling pathway.
Chamanara Mohsen,Rashidian Amir,Mehr Shahram Ejtemaei,Dehpour Ahmad-Reza,Shirkohi Reza,Akbarian Reyhaneh,Abdollahi Alireza,Rezayat Seyed-Mahdi
AIM:The aim of the present study is to investigate the anti-inflammatory effect of melatonin in trinitrobenzene sulfonic acid (TNBS)-induced rat colitis through the inhibition of Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signalling pathway and activation of melatonin receptor. METHODS:Colitis was induced in Wistar rats by administration of 100 mg/kg TNBS dissolved in 0.25 ml of 50% ethanol solution using a flexible plastic rubber catheter into the colon via the anus. This resulted in incidence of colitis on the first day, and all treatments were conducted for 10 days after induction of colitis. Melatonin was administered intraperitoneally (i.p.) at doses of 1, 5, and 10 mg/kg/day. Luzindole (non-selective MT1/MT2 receptor antagonist) was administered i.p. at dose of 5 mg/kg/day 15 min prior to melatonin injection. During the experiment, animals were monitored for the appearance of diarrhoea, body weight loss, and rectal bleeding. Myeloid peroxidase enzyme and tumour necrosis factor-α (TNF-α) activities were detected by immunohistochemistry. The protein expression level of TLR4, myeloid differentiation factor 88 (MyD88), NF-κB p65, and inhibitor of kappa B (I-κB) were detected by western blotting analysis. RESULTS:Treatment with melatonin improved weight loss, mucosal, and histological damage compared with TNBS group. In addition, melatonin decreased TNBS-induced up-regulation of TLR4, MyD88, and NF-κB p65, and increased down-regulation of I-κB proteins. On the other hand, the administration of luzindole resulted in the inhibition of melatonin effects. CONCLUSIONS:It seems that the inhibition of TLR4/NF-κB signalling pathway may mediate the anti-inflammatory effects of melatonin in TNBS-induced rat colitis.
Alterations in melatonin and 5-HT signalling in the colonic mucosa of mice with dextran-sodium sulfate-induced colitis.
MacEachern Sarah J,Keenan Catherine M,Papakonstantinou Evangelia,Sharkey Keith A,Patel Bhavik Anil
British journal of pharmacology
BACKGROUND AND PURPOSE:Inflammatory bowel disease (IBD) is characterized by pain, bleeding, cramping and altered gastrointestinal (GI) function. Changes in mucosal 5-HT (serotonin) signalling occur in animal models of colitis and in humans suffering from IBD. Melatonin is co-released with 5-HT from the mucosa and has a wide variety of actions in the GI tract. Here, we examined how melatonin signalling is affected by colitis and determined how this relates to 5-HT signalling. EXPERIMENTAL APPROACH:Using electroanalytical approaches, we investigated how 5-HT release, reuptake and availability as well as melatonin availability are altered in dextran sodium sulfate (DSS)-induced colitis in mice. Studies were conducted to explore if melatonin treatment during active colitis could reduce the severity of colitis. KEY RESULTS:We observed an increase in 5-HT and a decrease in melatonin availability in DSS-induced colitis. A significant reduction in 5-HT reuptake was observed in DSS-induced colitis animals. A reduction in the content of 5-HT was observed, but no difference in tryptophan levels were observed. A reduction in deoxycholic acid-stimulated 5-HT availability and a significant reduction in mechanically-stimulated 5-HT and melatonin availability were observed in DSS-induced colitis. Orally or rectally administered melatonin once colitis was established did not significantly suppress inflammation. CONCLUSION AND IMPLICATIONS:Our data suggest that DSS-induced colitis results in a reduction in melatonin availability and an increase in 5-HT availability, due to a reduction/loss of tryptophan hydroxylase 1 enzyme, 5-HT content and 5-HT transporters. Mechanosensory release was more susceptible to inflammation when compared with chemosensory release.
TLR2-Melatonin Feedback Loop Regulates the Activation of NLRP3 Inflammasome in Murine Allergic Airway Inflammation.
Wu Hui-Mei,Zhao Cui-Cui,Xie Qiu-Meng,Xu Juan,Fei Guang-He
Frontiers in immunology
Toll-like receptor 2 (TLR2) is suggested to initiate the activation of NLRP3 inflammasome, and considered to be involved in asthma. The findings that melatonin modulates TLRs-mediated immune responses, together with the suppressing effect of TLRs on endogenous melatonin synthesis, support the possibility that a feedback loop exists between TLRs system and endogenous melatonin synthesis. To determine whether TLR2-melatonin feedback loop exists in allergic airway disease and regulates NLRP3 inflammasome activity, wild-type (WT) and TLR2 mice were challenged with OVA to establish allergic airway disease model. Following OVA challenge, WT mice exhibited increased-expression of TLR2, activation of NLRP3 inflammasome and marked airway inflammation, which were all effectively inhibited in the TLR2 mice, indicating that TLR2-NLRP3 mediated airway inflammation. Meanwhile, melatonin biosynthesis was reduced in OVA-challenged WT mice, while such reduction was notably rescued by TLR2 deficiency, suggesting that TLR2-NLRP3-mediated allergic airway inflammation was associated with decreased endogenous melatonin biosynthesis. Furthermore, addition of melatonin to OVA-challenged WT mice pronouncedly ameliorated airway inflammation, decreased TLR2 expression and NLRP3 inflammasome activation, further implying that melatonin in turn inhibited airway inflammation via suppressing TLR2-NLRP3 signal. Most interestingly, although melatonin receptor antagonist luzindole significantly reduced the protein expressions of ASMT, AANAT and subsequent level of melatonin in OVA-challenged TLR2 mice, it exhibited null effect on leukocytes infiltration, Th2-cytokines production and NLRP3 activity. These results indicate that a TLR2-melatonin feedback loop regulates NLRP3 inflammasome activity in allergic airway inflammation, and melatonin may be a promising therapeutic medicine for airway inflammatory diseases such as asthma.
Toll-like receptor 6 stimulation promotes T-helper 1 and 17 responses in gastrointestinal-associated lymphoid tissue and modulates murine experimental colitis.
Morgan M E,Koelink P J,Zheng B,den Brok M H M G M,van de Kant H J G,Verspaget H W,Folkerts G,Adema G J,Kraneveld A D
T-helper 1 and 17 (Th1/Th17) responses are important in inflammatory bowel disease (IBD), and research indicates that Toll-like receptor 6 (TLR6) stimulation leads to Th17 cell development within the lung. The gastrointestinal tract, like the lung, is a mucosal surface that is exposed to bacterially derived TLR6 ligands. Thus, we looked at the effects of TLR6 stimulation on the expression of Th17-, Th1-, and regulatory T-cell-associated transcription factors; RORγt, T-bet, and Foxp3, respectively; in CD4+ T cells within gut-associated lymphoid tissue (GALT) in vitro and in vivo. Cells from GALT and spleen were stimulated with anti-CD3 and TLR ligands for TLR1/2 and TLR2/6 (Pam3CSK4 and FSL-1, respectively). FSL-1 was more effective than Pam3CSK4 at inducing Th1 and Th17 responses in the GALT while Pam3CSK4 rivaled FSL-1 in the spleen. TLR6 was further explored in vivo using experimental colitis. Tlr6-/- mice were resistant to colitis, and oral FSL-1 led to more severe colitis in wild-type mice. Similar pro-inflammatory reactions were seen in human peripheral blood mononuclear cells, and TLR6 expression was directly correlated with RORC mRNA levels in inflamed intestines of IBD patients. These results demonstrate that TLR6 supports Th1- and Th17-skewed responses in the GALT and might be an important target for the development of new medical interventions in IBD.