Intestinal Epithelium and Autophagy: Partners in Gut Homeostasis

Randall-Demllo, Sarron; Chieppa, Marcello; Eri, Rajaraman

doi:10.3389/fimmu.2013.00301

Cited by 98 publications

(79 citation statements)

References 119 publications

(146 reference statements)

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“…Moreover, our ImmunoChip study of 592 anti-TNF-treated IBD patients suggested that IRGM and HNF4G are involved in defining treatment response. Thus, these results support the involvement of microbes in defining treatment response, as IRGM and HNF4G encodes proteins involved in autophagy, whereby microbes in the gut are degraded [90,91]. Hence, our exploratory pharmacogenetic studies indicate that the genetic make-up of the host may define the response to anti-TNF treatment and may involve gut-microbe interactions.…”

Section: Discussionsupporting

confidence: 63%

Potential Impact of Diet on Treatment Effect from Anti-TNF Drugs in Inflammatory Bowel Disease

Andersen¹,

Hansen²,

Heitmann³

2017

Preprint

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Abstract:We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies for such investigations. PubMed was searched using specified search terms. One small prospective study on diet and anti-TNF treatment in 56 patients with CD found similar remission rates after 56 weeks among 32 patients with good compliance that received concomitant enteral nutrition and 24 with poor compliance that had no dietary restrictions (78% versus 67%, p = 0.51). A meta-analysis of 295 patients found higher odds of achieving clinical remission and remaining in clinical remission among patients on combination therapy with specialised enteral nutrition and Infliximab (IFX) compared with IFX monotherapy (OR 2.73; 95% CI: 1.73-4.31, p < 0.01, OR 2.93; 95% CI: 1.66-5.17, p < 0.01, respectively). In conclusion, evidence-based knowledge on impact of diet on anti-TNF treatment response for clinical use is scarce. Here we propose a mechanism by which Western style diet high in meat and low in fibre may promote colonic inflammation and potentially impact treatment response to anti-TNF drugs. Further studies using hypothesis-driven and data-driven strategies in observational, animal and interventional studies are warranted.

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Section: Discussionsupporting

confidence: 63%

Potential Impact of Diet on Treatment Effect from Anti-TNF Drugs in Inflammatory Bowel Disease

Andersen¹,

Hansen²,

Heitmann³

2017

Preprint

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“…Many studies report a link between autophagy and IBD, 96, 97 and in a study of the intracellular bacterium M. tuberculosis , 1,25-dihydroxyvitamin D 3 was shown to induce autophagy in human monocytes. 61 Our previously published work with Salmonella typhimurium, another intracellular pathogen, indicated that VDR-null mutant mice have worse outcomes with Salmonella -induced infection than wild-type controls.…”

Section: Discussionmentioning

confidence: 99%

Intestinal epithelial vitamin D receptor deletion leads to defective autophagy in colitis

Zhang

Lü

et al. 2014

Gut

303

317

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Objective Vitamin D and the vitamin D receptor (VDR) appear to be important immunological regulators of inflammatory bowel diseases (IBD). Defective autophagy has also been implicated in IBD, where interestingly, polymorphisms of genes such as ATG16L1 have been associated with increased risk. Although vitamin D, the microbiome, and autophagy are all involved in pathogenesis of IBD, it remains unclear whether these processes are related or function independently. Design We investigated the effects and mechanisms of intestinal epithelial VDR in healthy and inflamed states using cell culture models, a conditional VDR knockout mouse model (VDRΔIEC), colitis models, and human samples. Results Absence of intestinal epithelial VDR affects microbial assemblage and increases susceptibility to dextran sulfate sodium-induced colitis. Intestinal epithelial VDR down-regulates expressions of ATG16L1 and lysozyme, and impairs anti-microbial function of Paneth cells. Gain and loss of function assays showed that VDR levels regulate ATG16L1 and lysozyme at the transcriptional and translational levels. Moreover, low levels of intestinal epithelial VDR correlated with reduced ATG16L1 and representation by intestinal Bacteroides in IBD patients. Administration of the butyrate (a fermentation product of gut microbes) increases intestinal VDR expression and suppresses inflammation in a colitis model. Conclusions Our study demonstrates fundamental relationship between VDR, autophagy, and gut microbial assemblage that is essential for maintaining intestinal homeostasis, but also in contributing to the pathophysiology of IBD. These insights can be leveraged to define therapeutic targets for restoring VDR expression and function.

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“…In glucose or amino acid starved conditions, AMPK can directly regulate the ULK1 or VPS34-Beclin-1-ATG14 complexes to promote autophagy or indirectly inhibit mTOC1 activity and then promote ULK1-mediated phosphorylation of FIP200 and ATG13. Furthermore, ULK1 can also mediate autophagy through phosphorylation of Beclin-1 to form the VPS34-Beclin-1-ATG14 complex to activate autophagy [99,104,105]. …”

Section: Mammalian Target Of Rapamycin (Mtor) Pathwaymentioning

confidence: 99%

Role of Autophagy and Apoptosis in Non-Small-Cell Lung Cancer

Liu

Pei

Yang³

et al. 2017

IJMS

325

248

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Non-small-cell lung cancer (NSCLC) constitutes 85% of all lung cancers, and is the leading cause of cancer-related death worldwide. The poor prognosis and resistance to both radiation and chemotherapy warrant further investigation into the molecular mechanisms of NSCLC and the development of new, more efficacious therapeutics. The processes of autophagy and apoptosis, which induce degradation of proteins and organelles or cell death upon cellular stress, are crucial in the pathophysiology of NSCLC. The close interplay between autophagy and apoptosis through shared signaling pathways complicates our understanding of how NSCLC pathophysiology is regulated. The apoptotic effect of autophagy is controversial as both inhibitory and stimulatory effects have been reported in NSCLC. In addition, crosstalk of proteins regulating both autophagy and apoptosis exists. Here, we review the recent advances of the relationship between autophagy and apoptosis in NSCLC, aiming to provide few insights into the discovery of novel pathogenic factors and the development of new cancer therapeutics.

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Intestinal Epithelium and Autophagy: Partners in Gut Homeostasis

Cited by 98 publications

References 119 publications

Potential Impact of Diet on Treatment Effect from Anti-TNF Drugs in Inflammatory Bowel Disease

Potential Impact of Diet on Treatment Effect from Anti-TNF Drugs in Inflammatory Bowel Disease

Intestinal epithelial vitamin D receptor deletion leads to defective autophagy in colitis

Role of Autophagy and Apoptosis in Non-Small-Cell Lung Cancer

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