Akkermansia muciniphila mediates negative effects of IFNγ on glucose metabolism

Greer, Renee L.; Dong, Xiaoxi; Moraes, Ana Carolina Franco de; Zielke, Ryszard A.; Fernandes, Gabriel R.; Peremyslova, Ekaterina; Vasquez-Perez, Stephany; Schoenborn, Alexi A.; Gomes, Eduardo Nardini; Pereira, Alexandre C.; Ferreira, Sandra Roberta Gouvêa; Yao, Michael; Fuss, Ivan J.; Strober, Warren; Sikora, Aleksandra E.; Taylor, Gregory A.; Gulati, Ajay; Morgun, Andrey; Shulzhenko, Natalia

doi:10.1038/ncomms13329

Cited by 226 publications

(171 citation statements)

References 68 publications

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“…Host-gut microbiota interactions mediated by bile acids and LPS may affect macrophage polarization and host metabolism and immune responses 153 . For example, the gut microbe Akkermansia muciniphila has been recently shown to moderate the negative effects of IFN-γ on glucose tolerance in mice and humans 154 . These interactions will require further comprehensive investigation in patients with inflammatory and metabolic diseases.…”

Section: Macrophage and Adipocyte Dysfunction In Obese Adipose Tissuementioning

confidence: 99%

Macrophage functions in lean and obese adipose tissue

2017

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Summary Interactions between macrophages and adipocytes influence both metabolism and inflammation. Obesity-induced changes to macrophages and adipocytes lead to chronic inflammation and insulin resistance. This paper reviews the various functions of macrophages in lean and obese adipose tissue and how obesity alters adipose tissue macrophage phenotypes. Metabolic disease and insulin resistance shift the balance between numerous pro- and anti-inflammatory regulators of macrophages and create a feed-forward loop of increasing inflammatory macrophage activation and worsening adipocyte dysfunction. This ultimately leads to adipose tissue fibrosis and diabetes. The molecular mechanisms underlying these processes have therapeutic implications for obesity, metabolic syndrome, and diabetes.

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Section: Macrophage and Adipocyte Dysfunction In Obese Adipose Tissuementioning

confidence: 99%

Macrophage functions in lean and obese adipose tissue

2017

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“…Hence, in obese mice, an increase in number of Akkermansia muciniphila has been correlated with increased numbers of goblet cells [83]. Furthermore, Irgm1 was found to regulate the levels of Akkermansia muciniphila in a metabolic mouse model [84]. IRGM has been associated with IBD susceptibility and with anti-TNF response in IBD in a pilot study [85] (Hubenthal et al, unpublished).…”

Section: Discussionmentioning

confidence: 99%

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

2017

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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 prospective observational, animal and interventional studies are warranted.

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“…Hence, in obese mice, an increase in number of Akkermansia muciniphila has been correlated with increased numbers of goblet cells [86]. Furthermore, Irgm1 was found to regulate the levels of Akkermansia muciniphila in a metabolic mouse model [87]. IRGM has been associated with IBD susceptibility and with anti-TNF response in IBD in a pilot study [88] (Hubenthal et al, unpublished).…”

Section: Discussionmentioning

confidence: 99%

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.

show abstract

Akkermansia muciniphila mediates negative effects of IFNγ on glucose metabolism

Cited by 226 publications

References 68 publications

Macrophage functions in lean and obese adipose tissue

Macrophage functions in lean and obese adipose tissue

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

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