Autophagy controls mucus secretion from intestinal goblet cells by alleviating ER stress

Naama, Maria; Telpaz, Shahar; Awad, Aya; Ben-Simon, Shira; Harshuk-Shabso, Sarina; Modilevsky, Sonia; Rubin, Elad; Sawaed, Jasmin; Zelik, Lilach; Zigdon, Mor; Asulin, Nofar; Turjeman, Sondra; Werbner, Michal; Wongkuna, Supapit; Feeney, Rachel; Schroeder, Bjoern O.; Nyska, Abraham; Nuriel-Ohayon, Meital; Bel, Shai

doi:10.1016/j.chom.2023.01.006

Cited by 69 publications

(42 citation statements)

References 45 publications

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“…171 The mechanisms determining mucus secretion remain incompletely defined but are, in part, regulated by activation of autophagy and consequent reduction of endoplasmic reticulum stress, in a microbiota-dependent manner. 172 The presence of butyrate-producing bacteria promotes mucus production by goblet cells. 173 However, in the absence of sufficient SCFA availability, potentially due to low-fiber diet or dysbiosis, there is reduction in the mucosal barrier, linked both to reduced mucus production 173 and digestion of the mucosal barrier by commensal microbes.…”

Section: Mechanisms Linking Gut Microbiota To the Development Of Card...mentioning

confidence: 99%

Gut Microbiota and Microbial Metabolism in Early Risk of Cardiometabolic Disease

Gabriel

Ferguson

2023

Circulation Research

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Cardiometabolic disease comprises cardiovascular and metabolic dysfunction and underlies the leading causes of morbidity and mortality, both within the United States and worldwide. Commensal microbiota are implicated in the development of cardiometabolic disease. Evidence suggests that the microbiome is relatively variable during infancy and early childhood, becoming more fixed in later childhood and adulthood. Effects of microbiota, both during early development, and in later life, may induce changes in host metabolism that modulate risk mechanisms and predispose toward the development of cardiometabolic disease. In this review, we summarize the factors that influence gut microbiome composition and function during early life and explore how changes in microbiota and microbial metabolism influence host metabolism and cardiometabolic risk throughout life. We highlight limitations in current methodology and approaches and outline state-of-the-art advances, which are improving research and building toward refined diagnosis and treatment options in microbiome-targeted therapies.

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Section: Mechanisms Linking Gut Microbiota To the Development Of Card...mentioning

confidence: 99%

Gut Microbiota and Microbial Metabolism in Early Risk of Cardiometabolic Disease

Gabriel

Ferguson

2023

Circulation Research

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“…The protective effect of autophagy under HS conditions has been reflected in a study showing that arginine can alleviate intestinal damage by suppressing apoptosis and facilitating autophagy . Moreover, autophagy has been confirmed to be necessary for maintaining mucus production in goblet cells by relieving ERS . Even though autophagy plays a protective role during HS, prolonged exposure to high temperatures can lead to cell death and tissue damage …”

Section: Autophagy Links With Ers In Response To Hsmentioning

confidence: 99%

“…The intestinal chemical barrier refers to the intestinal fluid covering the surface of the intestinal epithelium, including mucus secreted by IECs, digestive juices, and antibacterial substances produced by the intestinal microbiota (e.g., mucin, lysozyme, defensins, and antimicrobial peptides) . Rich mucus improves the gut microbiome homeostasis, especially expanding mucus-utilizing bacteria (such as Akkermansia muciniphila ), which show the capacity of protecting against intestinal inflammation . Although sustained high temperature has been shown to trigger ERS and thus induce intestinal mucosa necrosis and shedding, the effects of HS on the intestinal chemical barrier have not yet received much attention and warrant additional studies.…”

Section: Hs-induced Disorders In Barrier Function and Microbial Metab...mentioning

confidence: 99%

“…97 Rich mucus improves the gut microbiome homeostasis, especially expanding mucus-utilizing bacteria (such as Akkermansia muciniphila), which show the capacity of protecting against intestinal inflammation. 75 Although sustained high temperature has been shown to trigger ERS and thus induce intestinal mucosa necrosis and shedding, 98 the effects of HS on the intestinal chemical barrier have not yet received much attention and warrant additional studies. The secretory capacity of the intestinal epithelium depends on ER homeostasis, particularly the generation of mucin and antimicrobial proteins.…”

Section: Hs-induced Disorders In Barrier Function and Microbial Metab...mentioning

confidence: 99%

“…67 Moreover, autophagy has been confirmed to be necessary for maintaining mucus production in goblet cells by relieving ERS. 75 Even though autophagy plays a protective role during HS, prolonged exposure to high temperatures can lead to cell death and tissue damage. 76…”

Section: Autophagy Links With Ers In Response To Hsmentioning

confidence: 99%

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Heat Stress-Induced Intestinal Barrier Impairment: Current Insights into the Aspects of Oxidative Stress and Endoplasmic Reticulum Stress

Tang

Yang

et al. 2023

J. Agric. Food Chem.

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Heat stress (HS) occurs when the sensible temperature of animals exceeds their thermoregulatory capacity, a condition that exerts a detrimental impact on health and growth. The intestinal tract, as a highly sensitive organ, has been shown to respond to HS by exhibiting mucosal injury, intestinal leakage, and disturbances in the gut microbiota. Oxidative stress and endoplasmic reticulum stress (ERS) are both potential outcomes of long-term exposure to high temperatures and have been linked to apoptosis, autophagy, and ferroptosis. In addition, HS alters the composition of the gut microbiota accompanied by changed levels of bacterial components and metabolites, rendering the gut more vulnerable to stress-related injury. In this review, we present recent advances in mechanisms of oxidative stress-associated ERS in response to HS, which is destructive to intestinal barrier integrity. The involvement of autophagy and ferroptosis in ERS was highlighted. Further, we summarize the relevant findings regarding the engagement of gut microbiota-derived components and metabolites in modulation of intestinal mucosal injury induced by HS.

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Curcumin and its anti‐colorectal cancer potential: From mechanisms of action to autophagy

Brockmueller,

Ruiz de Porras,

Shakibaei

2024

Phytotherapy Research

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Colorectal cancer (CRC) development and progression, one of the most common cancers globally, is supported by specific mechanisms to escape cell death despite chemotherapy, including cellular autophagy. Autophagy is an evolutionarily highly conserved degradation pathway involved in a variety of cellular processes, such as the maintenance of cellular homeostasis and clearance of foreign bodies, and its imbalance is associated with many diseases. However, the role of autophagy in CRC progression remains controversial, as it has a dual function, affecting either cell death or survival, and is associated with cellular senescence in tumor therapy. Indeed, numerous data have been presented that autophagy in cancers serves as an alternative to cell apoptosis when the latter is ineffective or in apoptosis‐resistant cells, which is why it is also referred to as programmed cell death type II. Curcumin, one of the active constituents of Curcuma longa, has great potential to combat CRC by influencing various cellular signaling pathways and epigenetic regulation in a safe and cost‐effective approach. This review discusses the efficacy of curcumin against CRC in vitro and in vivo, particularly its modulation of autophagy and apoptosis in various cellular pathways. While clinical studies have assessed the potential of curcumin in cancer prevention and treatment, none have specifically examined its role in autophagy. Nonetheless, we offer an overview of potential correlations to support the use of this polyphenol as a prophylactic or co‐therapeutic agent in CRC.

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Autophagy controls mucus secretion from intestinal goblet cells by alleviating ER stress

Cited by 69 publications

References 45 publications

Gut Microbiota and Microbial Metabolism in Early Risk of Cardiometabolic Disease

Gut Microbiota and Microbial Metabolism in Early Risk of Cardiometabolic Disease

Heat Stress-Induced Intestinal Barrier Impairment: Current Insights into the Aspects of Oxidative Stress and Endoplasmic Reticulum Stress

Curcumin and its anti‐colorectal cancer potential: From mechanisms of action to autophagy

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