scholarly journals Exploring the Mechanism of Indigo Naturalis in the Treatment of Ulcerative Colitis Based on TLR4/MyD88/NF-κB Signaling Pathway and Gut Microbiota

2021 ◽  
Vol 12 ◽  
Author(s):  
Qi-yue Yang ◽  
Le-le Ma ◽  
Chen Zhang ◽  
Jun-zhi Lin ◽  
Li Han ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Signal Transduction ◽  
Gut Microbiota ◽  
Intestinal Mucosa ◽  
Activity Index ◽  
Intestinal Flora ◽  
Physiological Status ◽  
Inflammatory Factor ◽  
Pathological Section ◽  
Indigo Naturalis

Background: Clinical trials have proven that indigo naturalis is a candidate drug for treating ulcerative colitis (UC), but its therapeutic mechanism is still unclear.Purpose: This study aimed to evaluate the protective effect and mechanism of indigo naturalis to treat mice with dextran sulfate sodium (DSS)-induced UC.Methods: DSS-induced UC mice were treated with indigo naturalis (200 mg/kg), indigo (4.76 mg/kg), and indirubin (0.78 mg/kg) for 1 week. The anti-UC mechanism of indigo naturalis was studied by pathological section, inflammatory factor, western blot, and 16S rRNA sequencing.Results: According to body weight change, disease activity index, and colon length, indigo naturalis had the strongest anti DSS-induced UC effect, followed by indirubin and indigo. Pathological section showed that indigo naturalis, indigo, and indirubin could reduce the infiltration of inflammatory cells, increase the secretion of intestinal mucus, and repair the intestinal mucosa. Indigo naturalis, indigo, and indirubin could reduce IL-1β,IL-6, and TNF-α by inhibiting TLR4/MyD88/NF-κB signal transduction. Indigo naturalis and indigo could also reduce IgA and IgG both in serum and colon tissue. In addition, indigo naturalis, indigo, and indirubin could adjust the gut microbiota structure of DSS-induced UC mice, reducing the ratio of Firmicutes/Bacteroidetes and increasing the abundance of probiotics.Conclusion: Indigo and indirubin are one of the main anti-UC components of indigo naturalis. INN could regulate intestinal flora, reduce inflammation, repair intestinal mucosa, and improve the physiological status of DSS-induced UC mice and its anti-UC mechanism may be involved in inhibiting TLR4/MyD88/NF-κB signal transduction.

scholarly journals Study on the mechanism of Indigo naturalis and its two main compounds (indigo and indirubin) in the treatment of ulcerative colitis based on TLR4/MyD88/NF-κB pathway and intestinal microorganisms

2020 ◽  
Author(s):  
Qi-yue Yang ◽  
Ya-nan He ◽  
Le-le Ma ◽  
Run-chun Xu ◽  
Nan Li ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Gut Microbiota ◽  
Intestinal Inflammation ◽  
Activity Index ◽  
Disease Activity Index ◽  
Pathological Section ◽  
Inflammatory Cytokine Production ◽  
Tnf Α ◽  
Indigo Naturalis ◽  
Inflammation Cytokines

Abstract Background: Indigo naturalis is a natural dye extracted from plants and has a good anti-inflammatory effect. Clinical studies have shown that it can improve ulcerative colitis (UC), but the active constituents and the mechanism are unclear. Methods: The anti-UC activity of Indigo naturalis and its two main compounds (indigo and indirubin) were investigated in dextran sulfate sodium (DSS)-induced UC mice. Indigo naturalis, indigo and indirubin were administrated to DSS-induced UC rats by oral gavage for 1 weeks. The anti-UC effect was evaluated by pathological section, inflammatory cytokine production, western blotting, and gut microbiota analysis via 16S rRNA sequencing. Results: Indigo naturalis, indigo and indirubin can improve the UC induced by DSS. Their effect intensity is Indigo naturalis > indirubin > indigo based on disease activity index, body weight, colon length and pathological section. Indigo naturalis, indigo and indirubin also decrease the expression of NF-κB，TLR4 and MYD88 proteins, thus reducing the level of related inflammation cytokines (IL-1β, IL-6 and TNF-α) both in serum and tissue. In addition, Indigo naturalis and indigo improved symptoms of gut microbial disturbance, and decreased Firmicutes/Bacteroidetes ratio and the significantly increased probiotics such as Lactobacillus. Indirubin has little effect on the regulation of gut microbial. Conclusions: Indigo naturalis could attenuate the DSS-induced UC in mice, by means of ameliorating intestinal inflammation, improving intestinal mucosa, and regulating the disturbed gut microbiota. Indigo and indirubin could also attenuate the DSS-induced UC in mice, but their comprehensive effect is not as good as Indigo naturalis.

Desmethylbellidifolin Attenuates Dextran Sulfate Sodium-Induced Colitis: Impact on Intestinal Barrier, Intestinal Inflammation and Gut Microbiota

Planta Medica ◽  
2021 ◽  
Author(s):  
Jiaqi Wu ◽  
Yuzheng Wu ◽  
Yue Chen ◽  
Mengyang Liu ◽  
Haiyang Yu ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Gut Microbiota ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Intestinal Inflammation ◽  
Activity Index ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Function Evaluation ◽  
Biological Drugs

AbstractUlcerative colitis has been recognized as a chronic inflammatory disease predominantly disturbing the colon and rectum. Clinically, the aminosalicylates, steroids, immunosuppressants, and biological drugs are generally used for the treatment of ulcerative colitis at different stages of disease progression. However, the therapeutic efficacy of these drugs does not satisfy the patients due to the frequent drug resistance. Herein, we reported the anti-ulcerative colitis activity of desmethylbellidifolin, a xanthone isolated from Gentianella acuta, in dextran sulfate sodium-induced colitis in mice. C57BL/6 mice were treated with 2% dextran sulfate sodium in drinking water to induce acute colitis. Desmethylbellidifolin or balsalazide sodium was orally administrated once a day. Biological samples were collected for immunohistological analysis, intestinal barrier function evaluation, cytokine measurement, and gut microbiota analysis. The results revealed that desmethylbellidifolin alleviated colon shortening and body weight loss in dextran sulfate sodium-induced mice. The disease activity index was also lowered by desmethylbellidifolin after 9 days of treatment. Furthermore, desmethylbellidifolin remarkably ameliorated colonic inflammation through suppressing the expression of interleukin-6 and tumor necrosis factor-α. The intestinal epithelial barrier was strengthened by desmethylbellidifolin through increasing levels of occludin, ZO-1, and claudins. In addition, desmethylbellidifolin modulated the gut dysbiosis induced by dextran sulfate sodium. These findings suggested that desmethylbellidifolin effectively improved experimental ulcerative colitis, at least partly, through maintaining intestinal barrier integrity, inhibiting proinflammatory cytokines, and modulating dysregulated gut microbiota.

scholarly journals Ginger Alleviates DSS-Induced Ulcerative Colitis Severity by Improving the Diversity and Function of Gut Microbiota

2021 ◽  
Vol 12 ◽  
Author(s):  
Shanshan Guo ◽  
Wenye Geng ◽  
Shan Chen ◽  
Li Wang ◽  
Xuli Rong ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Gut Microbiota ◽  
Pathogenic Bacteria ◽  
Intestinal Flora ◽  
Experimental Models ◽  
Intestinal Microbiome ◽  
Control Group ◽  
Therapeutic Effects ◽  
Sequencing Analysis ◽  
And Function

The effects of ginger on gastrointestinal disorders such as ulcerative colitis have been widely investigated using experimental models; however, the mechanisms underlying its therapeutic actions are still unknown. In this study, we investigated the correlation between the therapeutic effects of ginger and the regulation of the gut microbiota. We used dextran sulfate sodium (DSS) to induce colitis and found that ginger alleviated colitis-associated pathological changes and decreased the mRNA expression levels of interleukin-6 and inducible nitric oxide synthase in mice. 16s rRNA sequencing analysis of the feces samples showed that mice with colitis had an intestinal flora imbalance with lower species diversity and richness. At the phylum level, a higher abundance of pathogenic bacteria, Proteobacteria and firmicutes, were observed; at the genus level, most samples in the model group showed an increase in Lachnospiraceae_NK4A136_group. The overall analysis illustrated an increase in the relative abundance of Lactobacillus_murinus, Lachnospiraceae_bacterium_615, and Ruminiclostridium_sp._KB18. These increased pathogenic bacteria in model mice were decreased when treated with ginger. DSS-treated mice showed a lower abundance of Muribaculaceae, and ginger corrected this disorder. The bacterial community structure of the ginger group analyzed with Alpha and Beta indices was similar to that of the control group. The results also illustrated that altered intestinal microbiomes affected physiological functions and adjusted key metabolic pathways in mice. In conclusion, this research presented that ginger reduced DSS-induced colitis severity and positively regulated the intestinal microbiome. Based on the series of data in this study, we hypothesize that ginger can improve diseases by restoring the diversity and functions of the gut microbiota.

scholarly journals Resveratrol Alleviates Dextran Sulfate Sodium-Induced Acute Ulcerative Colitis in Mice by Mediating PI3K/Akt/VEGFA Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Fang Zhu ◽  
Jujia Zheng ◽  
Fang Xu ◽  
Yiyuan Xi ◽  
Jun Chen ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Activity Index ◽  
Expression Patterns ◽  
Intestinal Flora ◽  
Inflammatory Factors ◽  
Akt Pathway ◽  
Sham Operation ◽  
Glycerol Phosphate

Ulcerative colitis (UC) is a chronic inflammatory disease that affects the colon, and its incidence is on the rise worldwide. Resveratrol (RSV), a polyphenolic compound, was recently indicated to exert anti-inflammatory effects on UC. Consequently, the current study was conducted to investigate the mechanism of RSV on alleviating UC in mice by mediating intestinal microflora homeostasis. First, potential targets that RSV may regulate UC were screened using the TCMSP database. Next, mice were treated differently, specifically subjected to sham-operation and dextran sulfate sodium (DSS) induction, and then treated or untreated with RSV. Disease Activity Index (DAI) and Hematoxylin-Eosin (HE) staining were employed to analyze the pathological changes of mice colon. In addition, the expression patterns of inflammatory factors in spleen tissues were detected using ELISA, while the protein expression patterns of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), and vascular endothelial growth factor A (VEGFA) in colon tissues were determined by means of immunohistochemistry (IHC) and Western blot analysis. Moreover, changes in intestinal flora and metabolite diversity in UC were analyzed by metabonomics. It was found that RSV played inhibitory roles in the PI3K/Akt pathway in mice. Meanwhile, the administration of RSV induced downregulated the expressions of TNF-α, IFN-γ, IL-1β, IL-6, and IL-4. The six floras of Haemophilus and Veillonella were significantly enriched in UC, while Clostridium, Roseburia, Akkermansia, and Parabacteroides were found to be enriched in control samples. Lastly, it was noted that Akkermansia could regulate the intestinal flora structure of UC mice through triacylglycerol biosynthesis, glycerol phosphate shuttle, cardiolipin biosynthesis, and other metabolic pathways to improve UC in mice. Altogether, our findings indicate that RSV suppressed the activation of the PI3K/Akt pathway and reduced the VEGFA gene expression to alleviate UC in mice.

scholarly journals Xiaoyaosan Improves Antibiotic-Induced Depressive-Like and Anxiety-Like Behavior in Mice Through Modulating the Gut Microbiota and Regulating the NLRP3 Inflammasome in the Colon

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenzhi Hao ◽  
Jiajia Wu ◽  
Naijun Yuan ◽  
Lian Gong ◽  
Junqing Huang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Nlrp3 Inflammasome ◽  
Target Genes ◽  
Intestinal Flora ◽  
Serum Levels ◽  
Inflammatory Factor ◽  
Depression And Anxiety ◽  
Colon Tissue ◽  
Caspase 1 ◽  
Behavioral Abnormalities

Disturbance of the gut microbiota plays an essential role in mental disorders such as depression and anxiety. Xiaoyaosan, a traditional Chinese medicine formula, has a wide therapeutic spectrum and is used especially in the management of depression and anxiety. In this study, we used an antibiotic-induced microbiome-depleted (AIMD) mouse model to determine the possible relationship between imbalance of the intestinal flora and behavioral abnormalities in rodents. We explored the regulatory effect of Xiaoyaosan on the intestinal flora and attempted to elucidate the potential mechanism of behavioral improvement. We screened NLRP3, ASC, and CASPASE-1 as target genes based on the changes in gut microbiota and explored the effect of Xiaoyaosan on the colonic NLRP3 pathway. After Xiaoyaosan intervention, AIMD mice showed a change in body weight and an improvement in depressive and anxious behaviors. Moreover, the gut flora diversity was significantly improved. Xiaoyaosan increased the abundance of Lachnospiraceae in AIMD mice and decreased that of Bacteroidaceae, the main lipopolysaccharide (LPS)-producing bacteria, resulting in decreased levels of LPS in feces, blood, and colon tissue. Moreover, serum levels of the inflammatory factor, IL-1β, and the levels of NLRP3, ASC, and CASPASE-1 mRNA and DNA in the colon were significantly reduced. Therefore, Xiaoyaosan may alleviate anxiety and depression by modulating the gut microbiota, correcting excessive LPS release, and inhibiting the immoderate activation of the NLRP3 inflammasome in the colon.

scholarly journals Anti-Inflammatory Effects of Mytilus coruscus Polysaccharide on RAW264.7 Cells and DSS-Induced Colitis in Mice

Marine Drugs ◽  
2021 ◽  
Vol 19 (8) ◽  
pp. 468
Author(s):  
Xing-Wei Xiang ◽  
Rui Wang ◽  
Li-Wen Yao ◽  
Yu-Fang Zhou ◽  
Pei-Long Sun ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Cytokines ◽  
Clinical Symptoms ◽  
Activity Index ◽  
Critical Role ◽  
Intestinal Flora ◽  
Intestinal Barrier ◽  
Raw264.7 Cells ◽  
Mytilus Coruscus ◽  
Anti Inflammatory

Considerable literature has been published on polysaccharides, which play a critical role in regulating the pathogenesis of inflammation and immunity. In this essay, the anti-inflammatory effect of Mytilus coruscus polysaccharide (MP) on lipopolysaccharide-stimulated RAW264.7 cells and a dextran sulfate sodium (DSS)-induced ulcerative colitis model in mice was investigated. The results showed that MP effectively promoted the proliferation of RAW264.7 cells, ameliorated the excessive production of inflammatory cytokines (TNF-α, IL-6, and IL-10), and inhibited the activation of the NF-κB signaling pathway. For DSS-induced colitis in mice, MP can improve the clinical symptoms of colitis, inhibit the weight loss of mice, reduce the disease activity index, and have a positive effect on the shortening of the colon caused by DSS, meliorating intestinal barrier integrity and lowering inflammatory cytokines in serum. Moreover, MP makes a notable contribution to the richness and diversity of the intestinal microbial community, and also regulates the structural composition of the intestinal flora. Specifically, mice treated with MP showed a repaired Firmicutes/Bacteroidetes ratio and an increased abundance of some probiotics like Anaerotruncus, Lactobacillus, Desulfovibrio, Alistipe, Odoribacter, and Enterorhabdus in colon. These data suggest that the MP could be a promising dietary candidate for enhancing immunity and protecting against ulcerative colitis.

scholarly journals Prevention and Curation of DSS-induced IBD in Mice With Bacillus Subtilis Fermented Milk via Inhibition of the Inflammatory Responses and Regulation of the Intestinal Flora

2020 ◽  
Author(s):  
Xuan Zhang ◽  
Yanjun Tong ◽  
Xiaomei Lyu ◽  
Jin Wang ◽  
Yuxue Wang ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Inflammatory Response ◽  
Oral Administration ◽  
Intestinal Mucosa ◽  
Inflammatory Responses ◽  
Activity Index ◽  
Intestinal Flora ◽  
Fermented Milk ◽  
Mucosal Barrier ◽  
Therapeutic Effects

Abstract Background: The pathogenesis of inflammatory bowel disease (IBD) might be related to the local inflammatory damage and the dysbacteriosis of intestinal flora. Probiotics can regulate the intestinal flora and ameliorate IBD. The probiotic Bacillus subtilis strain B. subtilis JNFE0126 was used as the starter of fermented milk. However, the therapeutic effects of B. subtilis fermented milk on IBD remains to be explored.Methods：The therapeutic effect of the B. subtilis fermented milk on DSS-induced IBD model mice was evaluated. The disease activity index (DAI) and the pathological features of small intestinal and colonic mucosa were examined. For exploring the action mechanism of B. subtilis, immunohistochemical staining and western-blotting were used to analyse the expression of the pro-inflammatory/anti-inflammatory cytokines, the proliferation of the intestinal stem cells, and the reconstruction of the mucosa barrier. The alteration of gut microbiota was investigated by taxonomic analysis.Results: The DAI of IBD was significantly decreased through oral administration of B. subtilis (JNFE0126) fermented milk, and the intestinal mucosa injury was attenuated. Moreover, B. subtilis could reduce the inflammatory response of the intestinal mucosa, induce proliferation of the intestinal stem cell, and promote reconstruction of the mucosal barrier. Furthermore, B. subtilis could rebalance the intestinal flora, increasing the abundance of Bacillus, Alistipes and Lactobacillus, while decreasing the abundance of Escherichia and Bacteroides.Conclusion: Oral administration of the B. subtilis fermented milk could alleviate DSS-induced IBD via inhibition of inflammatory response, promotion of the mucosal barrier reconstruction and regulation of the intestinal flora.

scholarly journals Naringin Exhibited Therapeutic Effects against DSS-Induced Mice Ulcerative Colitis in Intestinal Barrier–Dependent Manner

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6604
Author(s):  
Ruige Cao ◽  
Xing Wu ◽  
Hui Guo ◽  
Xin Pan ◽  
Rong Huang ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Therapeutic Potential ◽  
Activity Index ◽  
Biological Activities ◽  
Intestinal Flora ◽  
Intestinal Barrier ◽  
Disease Activity Index ◽  
Dietary Treatment ◽  
Therapeutic Effects ◽  
Dependent Manner

Naringin is a kind of multi-source food additive which has been explored broadly for its various biological activities and therapeutic potential. In the present study, the protective effect and mechanism of naringin on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice were investigated. The results showed that naringin significantly alleviated DSS-induced colitis symptoms, including disease activity index (DAI), colon length shortening, and colon pathological damage. The tissue and serum secretion of inflammatory cytokines, as well as the oxidative stress, were decreased accordingly upon naringin intervention. Naringin also decreased the proteins involved in inflammation and increased the expression of tight junction (TJ) proteins. Moreover, naringin increased the relative abundance of Firmicutes/Bacteroides and reduced the content of Proteobacteria to improve the intestinal flora disorder caused by DSS, which promotes the intestinal health of mice. It was concluded that naringin can significantly ameliorate the pathogenic symptoms of UC through inhibiting inflammatory response and regulating intestinal microbiota, which might be a promising natural therapeutic agent for the dietary treatment of UC and the improvement of intestinal symbiosis.

Impact of Gut Microbiota on Radiation-Associated Cognitive Dysfunction and Neuroinflammation in Mice

2022 ◽  
Author(s):  
Na Luo ◽  
Wenjun Zhu ◽  
Xiaoyu Li ◽  
Min Fu ◽  
Xiaohong Peng ◽  
...  
Keyword(s):  
Brain Injury ◽  
Cognitive Function ◽  
Gut Microbiota ◽  
Intestinal Flora ◽  
Inflammatory Factor ◽  
Sequencing Analysis ◽  
Partial Recovery ◽  
Intestinal Microbes ◽  
Gut Microbes ◽  
Radiation Induced

Radiation-induced brain injury is a common complication of brain irradiation that eventually leads to irreversible cognitive impairment. Evidence has shown that the gut microbiome may play an important role in radiation-induced cognitive function. However, the effects of gut microbiota on radiation-induced brain injury (RIBI) remain poorly understood. Here we studied the link between intestinal microbes and radiation-induced brain injury to further investigate the effects of intestinal bacteria on neuroinflammation and cognitive function. We first verified the differences in gut microbes between male and female mice and administered antibiotics to C57BL/6 male mice to deplete the gut flora and then expose mice to radiation. We found that depletion of intestinal flora after irradiation may act as a protective modulator against radiation-induced brain injury. Moreover, we found that pretreatment with depleted gut microbes in RIBI mice suppressed brain pro-inflammatory factor production, and high-throughput sequencing analysis of mouse feces at 1-month postirradiation revealed microbial differences. Interestingly, a proportion of Verrucomicrobia Akkermansia showed partial recovery. Additionally, short-chain fatty acid treatments increased neuroinflammation in the radiation-induced brain injury model. Although a further increase in cognitive function was not observed, brain injury was aggravated in whole-brain irradiated mice to some extent. The protective effects of depleted intestinal flora and the utilization of the brain-gut axis open new avenues for development of innovative therapeutic strategies for radiation-induced brain injury.

scholarly journals P125 Could gut microbiota metagenomic analysis improve diagnosis in paediatric Inflammatory Bowel Disease population?

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S216-S217
Author(s):  
G Pujol Muncunill ◽  
A Monleon-Getino ◽  
J Méndez-Viera ◽  
L Álvarez-Carnero ◽  
J Martin de Carpi
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Gut Microbiota ◽  
Diagnostic Tool ◽  
Bowel Disease ◽  
Inflammatory Markers ◽  
Activity Index ◽  
Healthy Controls ◽  
Inflammatory Bowel

Abstract Background Gut microbiota plays an important role in maintaining intestinal homeostasis. Recent studies postulate that dysbiosis may be involved in the pathogenesis of Inflammatory Bowel Disease (IBD). The aim of the study was to characterize the metagenomic biodiversity of the gut microbiota in Paediatric Inflammatory Bowel Disease patients (PIBD) and whether microbiome data could be used as diagnostic tool. Methods A prospective, longitudinal observational pilot clinical trial with consecutive inclusion of PIBD patients matched with healthy controls by age and sex was performed. A total of 36 children were planned to be included: 12 Crohn’s Disease (CD), 12 Ulcerative Colitis (UC) and 12 healthy controls (HC). Demographic, clinical and analytical data were recorded and stool and saliva samples were collected at onset, 3 and 6 months for DNA sequencing and bioinformatics analysis. Results Twenty-three patients (12CD, 11UC) and 9 HC were included (at the time of data analysis). Fifty-six percent were male; mean age: 11.7 years (IQR: 8–15). CD patients at onset had a mean Paediatric Crohn’s Disease Activity Index (PCDAI) of 22.5 (IQR: 10–55), a mean Faecal Calprotectin (FC) of 2384 mg/kg (IQR: 159–6000) and 83% of them had inflammatory markers elevation (Erythrocyte Sedimentation Rate (ESR) and/or C-reactive protein (CRP)). Patients with UC presented a mean Paediatric Ulcerative Colitis Activity Index (PUCAI) of 43.6 (IQR: 10–80) at onset, mean CF of 3381 mg/kg and 18% presented an increase of inflammatory markers (ESR and/or CRP). To date, Next Generation Sequencing (NGS) metagenomic study (saliva and stools) has been performed from 15 subjects (9 CD, 2 UC and 4 HC) at onset and 9 subjects (7 CD and 2 UC) at 3 months. A differential microbiota pattern was observed in both, saliva and stools, for CD at onset and at 3 months. In the stools, three differential taxa were found at onset of the disease and at 3 months and in saliva, another three differential taxa were observed compared to HC. In UC, 6 differential taxa (> 3 % diff. HC-UC, p-value=0) were selected in stools and 7 in saliva at onset compared to HC. Globally, a higher microbial biodiversity was observed for HC compared to CD at onset, but it was not statistically significant. Conclusion Provisional results showed a possible differential signature in both saliva and stools of patients with paediatric CD. These results must be validated with all the samples in process, and probably using larger paediatric cohorts before the development of these techniques as a diagnostic tool in the clinical practice.

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