Plant‐ and Fish‐Derived n‐3 PUFAs Suppress <i>Citrobacter Rodentium</i>–Induced Colonic Inflammation

Määttänen, Pekka; Lurz, Eberhard; Botts, Steven R.; Wu, Richard; Robinson, Shaiya C.; Yeung, Celine; Colas, Romain A.; Li, Bo; Johnson‐Henry, Kathene C.; Surette, Marc E.; Dalli, Jesmond; Sherman, Philip M.

doi:10.1002/mnfr.201900873

Cited by 14 publications

(9 citation statements)

References 51 publications

(80 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Manipulation of lipid content in host tissues, including omega-6 PUFAs such as arachidonic acid (C 20:4 ) and omega-3 PUFAs such as alpha-linoleic acid (C 18:3 ), eicosapentaenoic acid (C 20:5 ), and docosahexaenoic acid (C 22:6 ), through dietary, genetic, or pharmacological interventions is associated with altered severity of disease in numerous experimental models of colitis (55,56). In the context of enteric bacterial infection, the administration of different dietary oil supplements can alter disease outcomes in mice challenged with Citrobacter rodentium, a murine pathogen that serves as an established model for human EHEC and enteropathogenic E. coli (EPEC) infection (57)(58)(59)(60)(61). Given the high fat content and increased omega-6-to-omega-3 ratios characteristic of the Western diet, there is much interest in defining the molecular mechanisms by which specific PUFAs may modulate the outcomes of intestinal diseases such as enteric infection.…”

Section: Discussionmentioning

confidence: 99%

The Canonical Long-Chain Fatty Acid Sensing Machinery Processes Arachidonic Acid To Inhibit Virulence in Enterohemorrhagic Escherichia coli

Ellermann

Jimenez

Pifer

et al. 2021

mBio

View full text Add to dashboard Cite

The mammalian gastrointestinal tract is a complex biochemical organ that generates a diverse milieu of host- and microbe-derived metabolites. In this environment, bacterial pathogens sense and respond to specific stimuli, which are integrated into the regulation of their virulence programs. Previously, we identified the transcription factor FadR, a long-chain fatty acid (LCFA) acyl coenzyme A (acyl-CoA) sensor, as a novel virulence regulator in the human foodborne pathogen enterohemorrhagic Escherichia coli (EHEC). Here, we demonstrate that exogenous LCFAs directly inhibit the locus of enterocyte effacement (LEE) pathogenicity island in EHEC through sensing by FadR. Moreover, in addition to LCFAs that are 18 carbons in length or shorter, we introduce host-derived arachidonic acid (C20:4) as an additional LCFA that is recognized by the FadR system in EHEC. We show that arachidonic acid is processed by the acyl-CoA synthetase FadD, which permits binding to FadR and decreases FadR affinity for its target DNA sequences. This interaction enables the transcriptional regulation of FadR-responsive operons by arachidonic acid in EHEC, including the LEE. Finally, we show that arachidonic acid inhibits hallmarks of EHEC disease in a FadR-dependent manner, including EHEC attachment to epithelial cells and the formation of attaching and effacing lesions. Together, our findings delineate a molecular mechanism demonstrating how LCFAs can directly inhibit the virulence of an enteric bacterial pathogen. More broadly, our findings expand the repertoire of ligands sensed by the canonical LFCA sensing machinery in EHEC to include arachidonic acid, an important bioactive lipid that is ubiquitous within host environments. IMPORTANCE Polyunsaturated fatty acids (PUFAs) play important roles in host immunity. Manipulation of lipid content in host tissues through diet or pharmacological interventions is associated with altered severity of various inflammatory diseases. Our work introduces a defined host-pathogen interaction by which arachidonic acid, a host-derived and dietary PUFA, can impact the outcome of enteric infection with the human pathogen enterohemorrhagic Escherichia coli (EHEC). We show that long-chain fatty acids including arachidonic acid act as signaling molecules that directly suppress a key pathogenicity island in EHEC following recognition by the fatty acyl-CoA-responsive transcription factor FadR. Thus, in addition to its established effects on host immunity and its bactericidal activities against other pathogens, we demonstrate that arachidonic acid also acts as a signaling molecule that inhibits virulence in an enteric pathogen.

show abstract

Section: Discussionmentioning

confidence: 99%

The Canonical Long-Chain Fatty Acid Sensing Machinery Processes Arachidonic Acid To Inhibit Virulence in Enterohemorrhagic Escherichia coli

Ellermann

Jimenez

Pifer

et al. 2021

mBio

View full text Add to dashboard Cite

show abstract

“…In humans, the protective effect of n-3 FAs has been correlated with the decreased production of pro-inflammatory cytokines, through decreased alkaline phosphatase and bile duct injury. However, clinical trials addressing the benefit of n-3- PUFAs in IBD have yielded mixed results, with benefits differing based on the source of PUFA, suggesting differences in antiinflammatory activity between marine-derived n-3-PUFAS are superior to that derived from plants (48). Addressing the effectiveness of n-3-PUFAs has largely focused on marinederived fish oils on the notion that they provide EPA and DHA, whereas plant-derived n-3-PUFAs ALA and stearidonic acid are inefficiently converted to long-chain bioactive forms (49).…”

Section: Overall Fatty Acid Effect On Inflammation Is Variablementioning

confidence: 99%

“…Further, different FAs can exert the same antiinflammatory activity via different mechanisms. For instance, in C.Rodentium-colitis mice, supplementation with either fish or plant oil (flaxseed, ahiflower or sunflower) attenuated colitis, however fish oil reduced lipoxin and leukotriene B4 levels, whereas plant oils increased pro-resolving mediators D, E and T-series resolvins (48). The FA structure is also pivotal in disease outcome.…”

Section: Factors That Alter the Effect Of Fatty Acids (Pro Vs Anti-inflammatory)mentioning

confidence: 99%

Regulation of Intestinal Inflammation by Dietary Fats

et al. 2021

View full text Add to dashboard Cite

With the epidemic of human obesity, dietary fats have increasingly become a focal point of biomedical research. Epidemiological studies indicate that high-fat diets (HFDs), especially those rich in long-chain saturated fatty acids (e.g., Western Diet, National Health Examination survey; NHANES ‘What We Eat in America’ report) have multi-organ pro-inflammatory effects. Experimental studies have confirmed some of these disease associations, and have begun to elaborate mechanisms of disease induction. However, many of the observed effects from epidemiological studies appear to be an over-simplification of the mechanistic complexity that depends on dynamic interactions between the host, the particular fatty acid, and the rather personalized genetics and variability of the gut microbiota. Of interest, experimental studies have shown that certain saturated fats (e.g., lauric and myristic fatty acid-rich coconut oil) could exert the opposite effect; that is, desirable anti-inflammatory and protective mechanisms promoting gut health by unanticipated pathways. Owing to the experimental advantages of laboratory animals for the study of mechanisms under well-controlled dietary settings, we focus this review on the current understanding of how dietary fatty acids impact intestinal biology. We center this discussion on studies from mice and rats, with validation in cell culture systems or human studies. We provide a scoping overview of the most studied diseases mechanisms associated with the induction or prevention of Inflammatory Bowel Disease in rodent models relevant to Crohn’s Disease and Ulcerative Colitis after feeding either high-fat diet (HFD) or feed containing specific fatty acid or other target dietary molecule. Finally, we provide a general outlook on areas that have been largely or scarcely studied, and assess the effects of HFDs on acute and chronic forms of intestinal inflammation.

show abstract

“…In contrast, no effect on the peroxisome proliferator-activated receptor y (PPAR-γ) activation was observed ( 66 ). Some studies have observed exacerbating effects of flaxseed oil (being rich in C18:3n-3) on colitis in C. rodentium challenged mice despite increased n-3 PUFAs in intestinal tissues and increased caecal concentration of SCFAs (with proposed anti-inflammatory effects) ( 67 ). Other studies on plant oils have revealed that when mother rats during gestation and lactation were fed a diet high in safflower oil (around 72% C18:2n-6) compared to those fed diets high in canola oil (C18:3n-3) or high in oleic safflower oil (C18:1n-9), off-springs had more severe colitis ( 68 ).…”

Section: Plant-derived Fatty Acidsmentioning

confidence: 99%

Reducing Disease Activity of Inflammatory Bowel Disease by Consumption of Plant-Based Foods and Nutrients

et al. 2021

View full text Add to dashboard Cite

Inflammatory bowel disease is a chronic and recurring inflammatory condition of the gastrointestinal tract encompassing ulcerative colitis and Crohn's disease. Although the pathogenesis of inflammatory bowel disease remains to be fully elucidated, environmental factors such as diet are believed to play a pivotal role in the onset and management of inflammatory bowel disease. Diet is thought to play an essential role in intestinal inflammation due to its regulatory effects on the microbiota, gut immune system, and epithelial barrier function. Although the evidence remains insufficient to draw firm conclusions on the role of specific dietary components in gastrointestinal diseases, studies have suggested that a Western diet with high intakes of total fats, omega-6 fatty acids, and meat have been associated with intestinal inflammation and relapse of inflammatory bowel disease. In contrast to a Western diet, plant-based diets often result in a reduced intake of total fats and meats and an increased intake of plant fibers which may contribute to reduced intestinal inflammation. This review critically examines the influence of plant-based dietary components on the clinical disease course of inflammatory bowel disease. Furthermore, this review discusses the benefits and possible limitations of plant-derived dietary components in the treatment of inflammatory bowel disease while addressing the principal type of disease and the anatomic site of inflammation within the gastrointestinal tract. Finally, this review points out important directions for future research on the role of diet in inflammatory bowel disease. A better understanding of the role of diet and intestinal inflammation may pave the way for novel dietary interventions and specific foods- or food supplements, which can support the treatment of inflammatory bowel disease.

show abstract

Plant‐ and Fish‐Derived n‐3 PUFAs Suppress Citrobacter Rodentium–Induced Colonic Inflammation

Cited by 14 publications

References 51 publications

The Canonical Long-Chain Fatty Acid Sensing Machinery Processes Arachidonic Acid To Inhibit Virulence in Enterohemorrhagic Escherichia coli

The Canonical Long-Chain Fatty Acid Sensing Machinery Processes Arachidonic Acid To Inhibit Virulence in Enterohemorrhagic Escherichia coli

Regulation of Intestinal Inflammation by Dietary Fats

Reducing Disease Activity of Inflammatory Bowel Disease by Consumption of Plant-Based Foods and Nutrients

Contact Info

Product

Resources

About