Helminth infection protects against high fat diet-induced obesity via induction of alternatively activated macrophages

Su, Chien-Wen; Chen, Chih-Yu; Li, Yali; Long, Stuart A.; Massey, William; Kumar, Deepak; Walker, W. Allan; Shi, Hai Ning

doi:10.1038/s41598-018-22920-7

Cited by 64 publications

(70 citation statements)

References 59 publications

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“…Experiments from our laboratory and others have shown that helminth infections attenuate obesity induced by HFD in mouse models, 15,[20][21][22] supporting the inverse correlation between helminth infections and obesity observed in clinical studies. In the current work, we investigated whether the protective effect of helminth infection against HFD obesity is dependent on the H polygyrus-induced Th2 immune response.…”

Section: H Polygyrus Infection Protects Wild-type But Not Stat6 -/-Misupporting

confidence: 76%

“…[12][13][14] We have shown recently that infection of mice with the intestinal helminth parasite H polygyrus significantly attenuated high-fat diet (HFD)induced obesity and that this attenuation was associated with enhanced Th2/Treg responses and M2 macrophage polarization. 15 The intestinal microbiota is a complex and dynamic ecosystem, which is composed of trillions of microbes that reside in the gut and plays a significant role in health and disease. 16 It has been found that the composition of the intestinal microbiota differs between obese and healthy people and that altering the microbiota can alleviate obesity.…”

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confidence: 99%

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Helminth-Induced and Th2-Dependent Alterations of the Gut Microbiota Attenuate Obesity Caused by High-Fat Diet

Chen

Jiao

et al. 2020

Cellular and Molecular Gastroenterology and Hepatology

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Work from our laboratory and others show that helminth infection attenuates HFD-induced obesity. This current study demonstrates that helminth infection protects against HFD-induced obesity through helminth-induced, Th2dependent alterations of the intestinal microbiota composition and functionality. BACKGROUND & AIMS: Epidemiological and animal studies have indicated an inverse correlation between the rising prevalence of obesity and metabolic syndrome and exposure to helminths. Whether helminth-induced immune response contributes to microbiota remodeling in obesity remains unknown. The aim of this study is to explore the immune-regulatory role of helminth in the prevention of HFD-induced obesity through remodeling gut microbiome. METHODS: C57BL/6J WT and STAT6-/mice were infected with Heligmosomoides polygyrus and followed by high fat diet (HFD) feeding for 6 weeks. The host immune response, body weight, and fecal microbiota composition were analyzed. We used adoptive transfer of M2 macrophages and microbiota transplantation approaches to determine the impact of these factors on HFD-obesity. We also examined stool microbiota composition and short chain fatty acids (SCFAs) concentration and determined the expression of SCFA-relevant receptors in the recipient mice. RESULTS: Helminth infection of STAT6-/-(Th2-deficient) mice and adoptive transfer of helminth-induced alternatively activated (M2) macrophages demonstrated that the helminth-associated Th2 immune response plays an important role in the protection against obesity and induces changes in microbiota composition. Microbiota transplantation showed that helminth-induced, Th2-dependent alterations of the gut microbiota are sufficient to confer protection against obesity. Collectively, these results indicate that helminth infection protects against HFD-induced obesity by Th2-dependent, M2 macrophage-mediated alterations of the intestinal microbiota. CONCLUSION: Our findings provide new mechanistic insights into the complex interplay between helminth infection, the immune system and the gut microbiota in a HFD-induced obesity model and holds promise for gut microbiome-targeted immunotherapy in obesity prevention.

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Section: H Polygyrus Infection Protects Wild-type But Not Stat6 -/-Misupporting

confidence: 76%

mentioning

confidence: 99%

Helminth-Induced and Th2-Dependent Alterations of the Gut Microbiota Attenuate Obesity Caused by High-Fat Diet

Chen

Jiao

et al. 2020

Cellular and Molecular Gastroenterology and Hepatology

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“…In contrast, the prevalence of inflammatory metabolic diseases, such as Type 2 diabetes mellitus (T2DM) is high in high-income countries. The absence of exposure to helminth infections has been postulated as one mechanism to explain this markedly increased prevalence of T2DM [2][3][4][5][6]. Recent observational studies in India, Indonesia, China and Australia have reported that the prevalence of helminth infections was significantly lower in T2DM individuals compared to non-diabetic controls [4,5,7,8], thus confirming a protective effect of helminths against T2DM pathogenesis.…”

Section: Introductionmentioning

confidence: 98%

Helminth infection modulates systemic pro-inflammatory cytokines and chemokines implicated in type 2 diabetes mellitus pathogenesis

et al. 2020

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Background The prevalence of helminth infections exhibits an inverse association with the prevalence of Type 2 diabetes mellitus (T2DM), and helminths are postulated to mediate a protective effect against T2DM. However, the biological mechanism behind this effect is not known. Aims/Methods We postulated that helminth infections act by modulating the pro-inflammatory cytokine and chemokine milieu that is characteristic of T2DM. To examine the association of cytokines and chemokines in helminth-diabetes co-morbidity, we measured the plasma levels of a panel of pro-inflammatory cytokines and chemokines in individuals with Strongyloides stercoralis infection (Ss+) and T2DM at the time of Ss diagnosis and then 6 months after definitive anthelmintic treatment along with uninfected control individuals with T2DM alone (Ss-). Principal findings Ss+ individuals exhibited significantly diminished levels of the pro-inflammatory cytokines-IL-1α, IL-1β, IL-6, IL-12, IL-18, IL-23, IL-27, G-CSF and GM-CSF and chemokines-CCL1, CCL2, CCL3, CCL11, CXCL1, CXCL2, CXCL8, CXCL9, CXCL10 and CXCL11. In contrast, Ss+ individuals exhibited significantly elevated levels of IL-1Ra. Anthelmintic treatment resulted in increased levels of all of the cytokines and chemokines. Conclusions Thus, helminth infections alleviate and anthelmintic therapy partially restores the plasma cytokine and chemokine levels in helminth-diabetes co-morbidity. Our data therefore offer a plausible biological mechanism for the protective effect of helminth infections against T2DM.

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“…The first study by Su and colleagues showed that H. polygyrus infection provided protection against DIO by increasing thermogenesis via M2 macrophage recruitment (Figure 2). 69 The second study by Shimokawa et. al.…”

Section: Impact Of Helminth Infection On Type 2 Immune Cell Function mentioning

confidence: 99%

“…Finally, two other studies used H. polygyrus, a natural murine helminth, to investigate the ability of infection to induce adaptive thermogenesis . The first study by Su and colleagues showed that H. polygyrus infection provided protection against DIO by increasing thermogenesis via M2 macrophage recruitment (Figure ) . The second study by Shimokawa et.…”

Section: Helminth Infection and Metabolic Statusmentioning

confidence: 99%

The interplay of type 2 immunity, helminth infection and the microbiota in regulating metabolism

2019

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Type 2 immunity has recently emerged as a critical player in metabolic status, with numerous studies investigating the role of type 2 immune cells within adipose tissue. Metabolic dysfunction is often characterised as a low‐grade or chronic inflammatory state within tissues, and type 2 immunity may facilitate a return to metabolic homeostasis. A complex network of type 2 resident cells including M2 macrophages, eosinophils and ILC2s has been identified within adipose tissue. Although the effector cells in this equilibrium have not been clearly identified, any alteration of the type 2 microenvironment resulted in an altered metabolic state. Historically, the type 2 immune response has been associated with helminth infection. The type 2 immune response drives host resistance and plays an important role in promoting tissue repair following the migration of helminth larvae through tissues. Although helminths are largely eradicated in developed countries, infection rates remain high in poor communities within the developing world. Interestingly, there is strong evidence that helminth infection is inversely correlated with autoimmune or inflammatory disorders. Recently, an increasing amount of epidemiological and field studies suggest that it could be the same for obesity and metabolic syndrome. In the current review, we summarise the literature linking type 2 immunity to improved adipose tissue function. We then discuss more recent evidence indicating that helminth infection can provide protection against metabolic syndrome. Lastly, we explore the possible contributions of altered nutrient uptake, adipose tissue function and/or the intestinal microbiota with the ability of helminths to alter metabolic status.

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Helminth infection protects against high fat diet-induced obesity via induction of alternatively activated macrophages

Cited by 64 publications

References 59 publications

Helminth-Induced and Th2-Dependent Alterations of the Gut Microbiota Attenuate Obesity Caused by High-Fat Diet

Helminth-Induced and Th2-Dependent Alterations of the Gut Microbiota Attenuate Obesity Caused by High-Fat Diet

Helminth infection modulates systemic pro-inflammatory cytokines and chemokines implicated in type 2 diabetes mellitus pathogenesis

The interplay of type 2 immunity, helminth infection and the microbiota in regulating metabolism

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