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1.
Int J Biol Sci ; 18(1): 199-213, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34975327

RESUMO

Autoimmune hepatitis (AIH) is an immune-mediated chronic inflammatory liver disease, and its pathogenesis is not fully understood. Our previous study discovered that receptor interacting protein kinase 3 (RIP3) is correlated with serum transaminase levels in AIH patients. However, its role and underlying mechanism in AIH are poorly understood. Here, we detected the increased expression and activation of RIP3 in livers of patients and animal models with AIH. The inhibition of RIP3 kinase by GSK872 prevented concanavalin A (ConA)-induced immune-mediated hepatitis (IMH) by reduced hepatic proinflammatory cytokines and immune cells including Th17 cells and macrophages. Further experiments revealed that RIP3 inhibition resulted in an increase in CD11b+Gr1+ myeloid-derived suppressor cells (MDSCs) with immunoregulatory properties in the liver, spleen, and peripheral blood. Moreover, the depletion of Gr-1+ MDSCs abrogated the protective effect and immune suppression function of GSK872 in ConA-induced IMH. Altogether, our data demonstrate that RIP3 blockade prevents ConA-induced IMH through promoting MDSCs infiltration. Inhibition of RIP3 kinase may be a novel therapeutic avenue for AIH treatment.

2.
Pharmacol Res ; : 106090, 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35065201

RESUMO

Evidence reveals that gut dysbiosis is involved in bidirectional interactions in gut-brain axis and participates in the progress of multiple disorders like anxiety. Gut microbes in early life are crucial for establishment of host health. We aimed to investigate whether early life probiotics Lactobacillus rhamnosus GG (LGG) colonization could relieve anxiety in adulthood through regulation of gut-brain axis. Live or fixed LGG was gavaged to C57BL/6 female mice from day 18 of pregnancy until natural birth, and newborn mice from day 1 to day 5 respectively. In this study, we found that live LGG could be effectively colonized in the intestine of offspring. LGG colonization increased intestinal villus length and colonic crypt depth, accompanied with barrier function protection before weaning. Microbiota composition by 16S rRNA sequencing showed that some beneficial bacteria, such as Akkermansia and Bifidobacteria, were abundant in LGG colonization group. The protective effect of LGG on gut microbiota persisted from weaning to adulthood. Intriguingly, behavioral results assessed by elevated plus mazed test and open field test demonstrated relief of anxiety-like behavior in adult LGG-colonized offspring. Mechanically, LGG colonization activated epithelial growth factor receptor (EGFR) and enhanced serotonin transporter (SERT) expression and modulated serotonergic system in the intestine, and increased brain-derived neurotrophic factor and γ-aminobutyric acid receptor levels in the hippocampus and amygdala. Blocking EGFR blunted LGG-induced the increased SERT and zonula occludens-1 expression. Collectively, early life LGG colonization could protect intestinal barrier of offspring and modulate gut-brain axis in association with relief of anxiety-like behavior in adulthood.

3.
Pharmacol Res ; : 106022, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34883213

RESUMO

Saccharomyces boulardii (S. boulardii) is a probiotic yeast that has been elucidated to be efficacious in fighting various gastrointestinal diseases in preclinical as well as clinical studies. Its general mechanisms of probiotic action in the treatment of gastrointestinal conditions cover multifaceted aspects, including immune regulation, production of antimicrobial substances, pathogen competitive elimination, gut barrier integrity maintenance, intestinal trophic effect and antioxidant potency. In this review, basic knowledge with regard to the gut-liver axis, available probiotics remedies and mechanistic insights of S. boulardii as probiotics will be elucidated. In addition, we summarize the therapeutic potential of S. boulardii in several liver diseases evident from both bench and bedside information, such as acute liver injury/failure, fibrosis, hepatic damages due to metabolic disturbance or infection and obstructive jaundice. Future prospects in relation to medicinal effects of S. boulardii are also exploited and discussed on the basis of novel and attractive therapeutic concept in the latest scientific literature.

4.
Front Nutr ; 8: 766350, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34901116

RESUMO

Mounting evidence has suggested the clinical significance of body composition abnormalities in the context of cirrhosis. Herein, we aimed to investigate the association between visceral adiposity and malnutrition risk in 176 hospitalized patients with cirrhosis. The adiposity parameters were obtained by computed tomography (CT) as follows: total adipose tissue index (TATI), visceral adipose tissue index (VATI), subcutaneous adipose tissue index (SATI), and visceral to subcutaneous adipose tissue area ratio (VSR). Malnutrition risk was screened using Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT). Visceral adiposity was determined given a higher VSR based on our previously established cutoffs. Multivariate analysis implicated that male gender (OR = 2.884, 95% CI: 1.360-6.115, p = 0.006), BMI (OR = 0.879, 95% CI: 0.812-0.951, P = 0.001), albumin (OR = 0.934, 95% CI: 0.882-0.989, P = 0.019), and visceral adiposity (OR = 3.413, 95% CI: 1.344-8.670, P = 0.010) were independent risk factors of malnutrition risk. No significant difference was observed regarding TATI, SATI, and VATI among patients with low or moderate and high risk of malnutrition. In contrast, the proportion of male patients embracing visceral adiposity was higher in high malnutrition risk group compared with that in low or moderate group (47.27 vs. 17.86%, p = 0.009). Moreover, this disparity was of borderline statistical significance in women (19.05 vs. 5.88%, p = 0.061). Assessing adipose tissue distribution might potentiate the estimation of malnutrition risk in cirrhotics. It is pivotal to recognize visceral adiposity and develop targeted therapeutic strategies.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34933958

RESUMO

BACKGROUND: The most widely used non-invasive screening tests for colorectal cancer (CRC) are faecal occult blood tests. Stool DNA test was developed in recent years. However, direct comparative analyses of these tests within the same population are still sparse. METHODS: 2842 participants who visited outpatient clinics or cancer screening centres were enrolled. Stool DNA test-I (KRAS, BMP3, NDRG4, and haemoglobin immunochemical tests), stool DNA test-II (SDC2 and SFRP2 tests) and FIT alone were performed and colonoscopy was used as the gold standard among 2240 participants. 42 and 302 participants had CRC and advanced adenomas (AA), respectively. RESULTS: The sensitivity for CRC of stool DNA test-I, -II and FIT was 90.5%, 92.9% and 81.0%, respectively. The sensitivity for advanced neoplasm (CRC plus AA) of stool DNA test-I, -II and FIT was 34.9%, 42.2% and 25.9%, respectively. The specificity of stool DNA test-I, -II and FIT was 91.4%, 93.3% and 96.8%, respectively, among those with negative results on colonoscopy. When the specificity of FIT was adjusted to match that of stool DNA tests by changing the threshold, no significant difference was seen in the sensitivities among the 3 tests for detecting CRC. For advanced neoplasm, the sensitivity of FIT was higher than DNA test-I and similar to DNA test-II under the same specificities. CONCLUSIONS: There was no significant advantage of the two stool DNA tests compared to FIT in detecting CRC or advanced neoplasm in this study. IMPACT: Our findings do not support extensive use of stool DNA tests instead of FIT.

6.
Crit Rev Microbiol ; : 1-18, 2021 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-34936854

RESUMO

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disease that disturbs the physiology and psychology of patients and increases the burden on families, the healthcare system, society, and economic development, affecting more and more people around the world. Despite the multiple factors that account for IBS remaining incompletely studied, emerging evidence demonstrated the abnormal changes in gut microbiota and bile acids (BAs) metabolism closely associated with IBS. Moreover, microbiota drives significant modifications for BAs, consisting of deconjugation, 7α-dehydroxylation, oxidation, epimerization, desulfation, esterification, and so on, while BAs, in turn, affect the microbiota directly or indirectly. In light of the complex connection among gut microbiota, BAs, and IBS, it is urgent to review the latest research progress in this field. In this review, we described the disorders of intestinal microecology and BAs profiles in IBS-D and also highlighted the cross-talk between gut microbiota and BAs in the context of IBS-D. Integrating these, we suggest that new therapeutic strategies targeting the microbiota-BAs axis for IBS-D, even for other related diseases caused by bacteria-bile acid dysbiosis should be expected.

7.
Front Immunol ; 12: 777665, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899735

RESUMO

Lactic acid, a metabolic by-product of host and intestinal microbiota, has been recovered as an active signal molecule in the immune system. In this study, a lactic acid biosynthesis pathway that directly produces lactic acid from glucose rather than ethanol with high production was reconstructed in Saccharomyces cerevisiae. The engineered S. cerevisiae showed anti-inflammatory activity in dextran sulfate sodium (DSS)-induced mice with improved histological damage, increased mucosal barrier, and decreased intestinal immune response. Lactic acid regulated the macrophage polarization state and inhibited the expression of pro-inflammatory cytokines in vivo and in vitro. Increasing the macrophage monocarboxylic acid transporter-mediated active lactic acid uptake suppressed the excessive activation of the NLRP3 inflammasome and the downstream caspase-1 pathway in macrophages. Moreover, lactic acid promoted histone H3K9 acetylation and histone H3K18 lactylation. Meanwhile, the engineered S. cerevisiae altered the diversity and composition of the intestinal microbiota and changed the abundance of metabolic products in mice with colitis. In conclusion, this study shows that the application of engineered S. cerevisiae attenuated DSS-induced colitis in mice via suppressing macrophage pyroptosis and modulating the intestinal microbiota, which is an effective and safe treatment strategy for ulcerative colitis.

8.
Front Nutr ; 8: 756565, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722615

RESUMO

Scope: Gut microbiome-derived metabolites are the major mediators of diet-induced host-microbial interactions. Aryl hydrocarbon receptor (AHR) plays a crucial role in glucose, lipid, and cholesterol metabolism in the liver. In this study, we aimed to investigate the role of indole-3-acetic acid (IAA) and AHR in sulforaphane (SFN) alleviates hepatic steatosis in mice fed on a high-fat diet (HFD). Methods and Results: The HFD-fed male C57BL/6 mice were intervened with SFN for 6 weeks. HFD-mice showed classical pathophysiological characteristics of hepatic steatosis. The results showed that SFN significantly reduced body weight, liver inflammation and hepatic steatosis in HFD-fed mice. SFN reduced hepatic lipogenesis by activating AHR/SREBP-1C pathway, which was confirmed in HepG2 cell experiments. Moreover, SFN increased hepatic antioxidant activity by modulating Nrf-2/NQO1 expression. SFN increased serum and liver IAA level in HFD mice. Notably, SFN manipulated the gut microbiota, resulting in reducing Deferribacteres and proportions of the phylum Firmicutes/Bacteroidetes and increasing the abundance of specific bacteria that produce IAA. Furthermore, SFN upregulated Ahr expression and decreased the expression of inflammatory cytokines in Raw264.7 cells. Conclusions: SFN ameliorated hepatic steatosis not only by modulating lipid metabolism via AHR/SREBP-1C pathway but regulating IAA and gut microbiota in HFD-induced NAFLD mice.

9.
J Am Coll Cardiol ; 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34752902

RESUMO

BACKGROUND: Gastrointestinal bleeding is the most frequent major complication of antiplatelet therapy. In patients at low bleeding risk, however, clinically overt gastrointestinal bleeding is relatively uncommon. OBJECTIVE: We sought to assess the effects of different antiplatelet regimens on gastrointestinal mucosal injury using a novel magnetically-controlled capsule endoscopy system in patients at low bleeding risk. METHODS: Patients (n=505) undergoing percutaneous coronary intervention in whom capsule endoscopy demonstrated no ulcerations or bleeding (although erosions were permitted) after 6 months of dual antiplatelet therapy (DAPT) were randomly assigned to aspirin plus placebo (n=168), clopidogrel plus placebo (n=169), or aspirin plus clopidogrel (n=168) for an additional 6 months. The primary endpoint was the incidence of gastrointestinal mucosal injury (erosions, ulceration, or bleeding) at 6-month or 12-month capsule endoscopy. RESULTS: Gastrointestinal mucosal injury through 12 months was less with single antiplatelet therapy (SAPT) compared with DAPT (94.3% vs. 99.2%, P=0.02). Aspirin and clopidogrel monotherapy had similar effects. Among 68 patients without any gastrointestinal injury at randomization (including no erosions), SAPT compared with DAPT caused less gastrointestinal injury (68.1% vs. 95.2%, P=0.006), including fewer new ulcers (8.5% vs. 38.1%, P=0.009). Clinical gastrointestinal bleeding between 6 and 12 months was less with SAPT compared with DAPT (0.6% vs. 5.4%, P=0.001). CONCLUSIONS: Despite being at low risk of bleeding, nearly all patients receiving antiplatelet therapy developed gastrointestinal injury, although overt bleeding was infrequent. DAPT for 6 months followed by SAPT with aspirin or clopidogrel between 6 and 12 months resulted in less gastrointestinal mucosal injury and clinical bleeding compared with DAPT through 12 months.

10.
Front Immunol ; 12: 700995, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804005

RESUMO

The prevalence of inflammatory bowel disease (IBD) is increasing worldwide and correlates with dysregulated immune response because of gut microbiota dysbiosis. Some adverse early life events influence the establishment of the gut microbiota and act as risk factors for IBD. Prenatal maternal stress (PNMS) induces gut dysbiosis and perturbs the neuroimmune network of offspring. In this study, we aimed to investigate whether PNMS increases the susceptibility of offspring to colitis in adulthood. The related index was assessed during the weaning period and adulthood. We found that PNMS impaired the intestinal epithelial cell proliferation, goblet cell and Paneth cell differentiation, and mucosal barrier function in 3-week-old offspring. PNMS induced low-grade intestinal inflammation, but no signs of microscopic inflammatory changes were observed. Although there was no pronounced difference between the PNMS and control offspring in terms of their overall measures of alpha diversity for the gut microbiota, distinct microbial community changes characterized by increases in Desulfovibrio, Streptococcus, and Enterococcus and decreases in Bifidobacterium and Blautia were induced in the 3-week-old PNMS offspring. Notably, the overgrowth of Desulfovibrio persisted from the weaning period to adulthood, consistent with the results observed using fluorescence in situ hybridization in the colon mucosa. Mechanistically, the fecal microbiota transplantation experiment showed that the gut microbiota from the PNMS group impaired the intestinal barrier function and induced low-grade inflammation. The fecal bacterial solution from the PNMS group was more potent than that from the control group in inducing inflammation and gut barrier disruption in CaCo-2 cells. After treatment with a TNF-α inhibitor (adalimumab), no statistical difference in the indicators of inflammation and intestinal barrier function was observed between the two groups. Finally, exposure to PNMS remarkably increased the values of the histopathological parameters and the inflammatory cytokine production in a mouse model of experimental colitis in adulthood. These findings suggest that PNMS can inhibit intestinal development, impair the barrier function, and cause gut dysbiosis characterized by the persistent overgrowth of Desulfovibrio in the offspring, resulting in exacerbated experimental colitis in adulthood.

11.
Cancer Sci ; 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34811848

RESUMO

A high-fat diet (HFD) leads to long-term exposure to gut microbial metabolite secondary bile acids, such as deoxycholic acid (DCA), in the intestine, which is closely linked to colorectal cancer (CRC). Evidence reveals that vasculogenic mimicry (VM) is a critical event for the malignant transformation of cancer. Therefore, this study investigated the crucial roles of DCA in the regulation of VM and the progression of intestinal carcinogenesis. The effects of an HFD on VM formation and epithelial-mesenchymal transition (EMT) in human CRC tissues were investigated. The fecal DCA level was detected in HFD-treated Apcmin/+ mice. Then the effects of DCA on VM formation, EMT, and vascular endothelial growth factor receptor 2 (VEGFR2) signaling were evaluated in vitro and in vivo. Here we demonstrated that compared with a normal diet, an HFD exacerbated VM formation and EMT in CRC patients. An HFD could alter the composition of the gut microbiota and significantly increase the fecal DCA level in Apcmin/+ mice. More importantly, DCA promoted tumor cell proliferation, induced EMT, increased VM formation, and activated VEGFR2, which led to intestinal carcinogenesis. In addition, DCA enhanced the proliferation and migration of HCT-116 cells, and induced EMT process and vitro tube formation. Furthermore, the silence of VEGFR2 reduced DCA-induced EMT, VM formation, and migration. Collectively, our results indicated that microbial metabolite DCA promoted VM formation and EMT through VEGFR2 activation, which further exacerbated intestinal carcinogenesis.

12.
Food Funct ; 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34821899

RESUMO

Research has shown that maternal sucralose (MS) exposure alters the gut microbiota of offspring at weaning and predisposes the offspring to developing obesity, non-alcoholic fatty liver disease and metabolic syndrome later in life. However, the underlying mechanism remains unclear. Paneth cells are thought to critically influence the gut microbiota. This study aimed to investigate whether MS exposure induced Paneth cell defects and exacerbated gut dysbiosis of offspring. Female C57BL/6 mice were divided into the MS and control (water) groups during pregnancy and lactation. Progeny mice were fed a normal sucralose-free diet after weaning until adulthood. MS inhibited intestinal development and increased the expression of proinflammatory cytokines in the small intestines of 3-week-old progeny mice. MS increased the proportions of abnormal granule secretion by Paneth cells. The number of Paneth cells and mRNA expression of AMPs such as cryptdins and lysozyme were reduced in the MS group. MS disturbed the gut microbiota composition and diversity in the 3-week-old offspring mice. The relative abundances of pro-inflammatory bacteria, such as Desulfovibrionales, Helicobacter, Pasteurellales and Campylobacterales were significantly increased in the MS group, while anti-inflammatory bacteria, including Clostridium XI, were decreased. This dysbiosis continued into adulthood. These findings showed that MS exposure induced Paneth cell defects and exacerbated gut dysbiosis in offspring mice. Sucralose should be consumed with caution, especially during pregnancy and in early life.

13.
Cancer Lett ; 526: 225-235, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34843863

RESUMO

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death worldwide. It involves the complex interactions between genetic factors, environmental exposure, and gut microbiota. Specific changes in the gut microbiome and metabolome have been described in CRC, supporting the critical role of gut microbiota dysbiosis and microbiota-related metabolites in the tumorigenesis process. Short-chain fatty acids (SCFAs), the principal metabolites generated from the gut microbial fermentation of insoluble dietary fiber, can directly activate G-protein-coupled receptors (GPCRs), inhibit histone deacetylases (HDACs), and serve as energy substrates to connect dietary patterns and gut microbiota, thereby improving the intestinal health. A significantly lower abundance of SCFAs and SCFA-producing bacteria has been demonstrated in CRC, and the supplementation of SCFA-producing probiotics can inhibit intestinal tumor development. SCFAs-guided modulation in both mouse and human CRC models augmented their responses to chemotherapy and immunotherapy. This review briefly summarizes the complex crosstalk between SCFAs and CRC, which might inspire new approaches for the diagnosis, treatment and prevention of CRC on the basis of gut microbiota-derived metabolites SCFAs.

14.
Oxid Med Cell Longev ; 2021: 3328505, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804363

RESUMO

Inflammaging refers to chronic, low-grade inflammation during aging, which contributes to the pathogenesis of age-related diseases. Studies have shown that probiotic intervention in the aging stage could delay aging-related disorders. However, whether the application of probiotics in early life could have antiaging effects on offspring was unknown. Here, we investigated the effects of Lactobacillus rhamnosus GG (LGG) colonization in early life on inflammaging of offspring. Pregnant mice with the same conception time were given LGG live bacteria (LC group) or LGG fixed bacteria (NC group) from the 18th day after pregnancy until natural birth. The progeny mice were treated with 107 cfu of live or fixed LGG for 0-5 days after birth, respectively. LGG colonization could be detected in the feces of 3-week offspring. The 16S rRNA sequencing analysis of 3-week-old offspring showed that colonization of LGG in early life could alter the composition and diversity of gut microbiota. Interestingly, the beneficial effects of LGG colonization in early life on the microbiota lasted to 8 months old. The abundance of longevity-related bacteria (Lactobacillus, Bifidobacterium, and Akkermansia muciniphila) increased significantly in the LGG colonization group. In addition, LGG colonization increased the abundance of short-chain fatty acid- (SCFA-) producing bacteria and the production of cecal SCFAs. LGG colonization in early life protected the intestinal barrier, enhanced antioxidant defense, attenuated epithelial cell DNA damage, and inhibited intestinal low-grade inflammation in 8-month-old progeny mice. Mechanically, LGG could upregulate Sirtuin1 (SIRT1)/Adenosine 5'-monophosphate-activated protein kinase (AMPK)/Peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) pathway and repress activation of nuclear factor-kappa B (NF-κB), while the protective effect of LGG was blunted after SIRT1 gene silencing. Together, LGG colonization in early life could ameliorate inflammaging of offspring, which would provide a new strategy for the prevention of age-related diseases.

15.
Front Oncol ; 11: 739648, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34733783

RESUMO

Accumulating evidence from studies in humans and animal models has elucidated that gut microbiota, acting as a complex ecosystem, contributes critically to colorectal cancer (CRC). The potential mechanisms often reported emphasize the vital role of carcinogenic activities of specific pathogens, but in fact, a series of metabolites produced from exogenous dietary substrates or endogenous host compounds occupy a decisive position similarly. Detrimental gut microbiota-derived metabolites such as trimethylamine-N-oxide, secondary bile acids, hydrogen sulfide and N-nitroso compounds could reconstruct the ecological composition and metabolic activity of intestinal microorganisms and formulate a microenvironment that opens susceptibility to carcinogenic stimuli. They are implicated in the occurrence, progression and metastasis of CRC through different mechanisms, including inducing inflammation and DNA damage, activating tumorigenic signaling pathways and regulating tumor immunity. In this review, we mainly summarized the intimate relationship between detrimental gut microbiota-derived metabolites and CRC, and updated the current knowledge about detrimental metabolites in CRC pathogenesis. Then, multiple interventions targeting these metabolites for CRC management were critically reviewed, including diet modulation, probiotics/prebiotics, fecal microbiota transplantation, as well as more precise measures such as engineered bacteria, phage therapy and chemopreventive drugs. A better understanding of the interplay between detrimental microbial metabolites and CRC would hold great promise against CRC.

16.
Front Physiol ; 12: 715852, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34690796

RESUMO

Recent studies have identified the critical role of microbiota in the pathophysiology of autoimmune liver diseases (AILDs), including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). Metagenomic studies reveal significant decrease of gut bacterial diversity in AILDs. Although profiles of metagenomic vary widely, Veillonella is commonly enriched in AIH, PBC, and PSC. Apart from gut microbiome, the oral and bile microbiome seem to be associated with these diseases as well. The functional analysis of metagenomics suggests that metabolic pathways changed in the gut microbiome of the patients. Microbial metabolites, including short-chain fatty acids (SCFAs) and microbial bile acid metabolites, have been shown to modulate innate immunity, adaptive immunity, and inflammation. Taken together, the evidence of host-microbiome interactions and in-depth mechanistic studies needs further accumulation, which will offer more possibilities to clarify the mechanisms of AILDs and provide potential molecular targets for the prevention and treatment in the future.

17.
Biochim Biophys Acta Rev Cancer ; 1876(2): 188626, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34520804

RESUMO

The human body harbors a vast array of microbiota that modulates host pathophysiological processes and modifies the risk of diseases including cancer. With the advent of metagenomic sequencing studies, the intratumoural microbiota has been found as a component of the tumor microenvironment, imperceptibly affecting the tumor progression and response to current antitumor treatments. The underlying carcinogenic mechanisms of intratumoural microbiota, mainly including inducing DNA damages, activating oncogenic signaling pathways and suppressing the immune response, differ significantly in varied organs and are not fully understood. Some native or genetically engineered microbial species can specifically accumulate and replicate within tumors to initiate antitumor immunity, which will be conducive to pursue precise cancer therapies. In this review, we summarized the community characteristics and therapeutic potential of intratumoural microbiota across diverse tumor types. It may provide new insights for a better understanding of tumor biology and hint at the significance of manipulating intratumoural microbiota.


Assuntos
Microbiota/imunologia , Neoplasias/imunologia , Microambiente Tumoral/imunologia , Humanos
18.
Front Nutr ; 8: 719176, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34532336

RESUMO

Both sleep-wake disturbance and malnutrition are common in cirrhosis and might be associated with similar adverse outcomes, such as impaired health-related quality of life, hepatic encephalopathy, and sarcopenia, but there is no study investigating the relationship between these two. We aimed to explore the relationship between sleep-wake disturbance [estimated by the Pittsburgh Sleep Quality Index (PSQI)] and malnutrition risk [estimated by the Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT)]. About 150 patients with cirrhosis were prospectively recruited. The nutritional risk is classified as low (0 points), moderate (1 point), and high (2-7 points) according to the RFH-NPT score. A global PSQI >5 indicated poor sleepers. Furthermore, multivariate linear regression analyses were performed to determine the relationship between sleep-wake disturbance and malnutrition. The median PSQI was seven, and RFH-NPT was two in the entire cohort, with 60.67 and 56.67% rated as poor sleep quality and high malnutrition risk, respectively. Patients with cirrhosis with poor sleep quality had significantly higher RFH-NPT score (3 vs. 1, P = 0.007). Our multivariate analyses indicated that male patients (ß = 0.279, P < 0.001), ascites (ß = 0.210, P = 0.016), and PSQI (ß = 0.262, P = 0.001) were independent predictors of malnutrition. In addition, the differences regarding PSQI score were more significant in male patients, as well as those >65 years or with Child-Turcotte-Pugh class A/B (CTP-A/B) or the median model for end-stage liver disease (MELD) <15. Taken together, the sleep-wake disturbance is strongly correlated with high malnutrition risk in patients with cirrhosis. Given sleep-wake disturbance is remediable, it is tempting to incorporate therapies to reverse poor sleep quality for improving nutritional status in patients with cirrhosis.

19.
Hepatol Commun ; 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34558226

RESUMO

It is essential to determine contributors around impairment in health-related quality of life (HRQoL) in patients with cirrhosis aiming at improving health care and therapeutic strategy. Studies simultaneously incorporating disease severity based on biochemical parameters and other physical/psychological effects (i.e., sleep disturbance and frailty) are heterogeneous and the subject of the present study. We analyzed and compared HRQoL, using the EuroQol Group 5 Dimension (EQ-5D) questionnaire and the utility index retrieved, in patients with cirrhosis and across groups stratified by sleep disturbance or frailty phenotype. Sleep disturbance and frailty were determined by the Pittsburgh Sleep Quality Index (PSQI) and Frailty Index, respectively. Multiple linear regression was implemented to clarify contributors of poor HRQoL. In this cohort of 227 patients with mean age of 61.7 years and 47.2% male, more than half of the study population represented impairment in HRQoL in at least one domain, according to EQ-5D. Furthermore, sleep disturbance and frailty have proved to be independently associated with poor HRQoL in two separate regression models, whereas conventional scoring systems such as Child-Pugh classification and Model for End-Stage Liver Disease are not closely relevant. Intriguingly, not all health domains within EQ-5D correlated well with PSQI and Frailty Index, with the exception of usual activities. Pain and anxiety/depression were the most frequently affected HRQoL domains even in patients without sleep disturbance or frailty. Conclusion: Impaired HRQoL is prevalent in patients with decompensated cirrhosis. Sleep disturbance and frailty are independently associated with poor HRQoL. It is imperative to timely intervene with these symptoms and deliver tailored health care.

20.
Biomed Res Int ; 2021: 7561645, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34552988

RESUMO

Background: Nonalcoholic steatohepatitis (NASH) can progress to cirrhosis and hepatic carcinoma and is closely associated with changes in the neurological environment. The discovery of new biomarkers would aid in the treatment of NASH. Methods: Data GSE89632 were downloaded from the Gene Expression Omnibus (GEO) database, and R package "limma" was used to identify differentially expressed genes (DEGs) for NASH vs. normal tissues. The STRING database was used to construct a protein-protein interaction (PPI) network, and the Cytoscape software program (Version 3.80) was used to visualize the PPI network and identify key genes. The immune infiltration of NASH was determined using the R package "CIBERSORT". Results: We screened 41 DEGs. GO and KEGG enrichment analyses of the DEGs revealed the enrichment of pathways related to NAFLD steatosis and inflammation. A PPI network analysis was also performed on the DEGs, and seven genes (MYC, CXCL8, FOS, SOCS1, SOCS3, IL6, and PTGS2) were identified as hub genes. An immune infiltration assessment revealed that macrophages M2, memory resting CD4+ T cells, and Î³Δ T cells play important roles in the immune microenvironment of NASH, which may be mediated by the seven identified hub genes.

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