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

Su, Chien-Wen; Chen, Chih-Yu; Jiao, Lefei; Long, Stuart A.; Mao, Tangyou; Ji, Qiaorong; O’Donnell, Shane; Stanton, Catherine; Zheng, Shasha; Walker, W. Allan; Cherayil, Bobby J.; Shi, Hai Ning

doi:10.1016/j.jcmgh.2020.06.010

Cited by 34 publications

(31 citation statements)

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“…Indeed, it was shown that the adoptive transfer of Th 17 cells contributed to metabolic homeostasis through an IL-17-dependent microbiota development ( 608 ). Moreover, it was demonstrated that the M2 macrophage-mediated helminth-associated Th2/Treg responses induce alterations in microbiota composition which was accompanied by protection against obesity ( 609 , 610 ).…”

Section: New Avenues For Adipose Tissue Immunomodulation In Metabolicmentioning

confidence: 99%

Adipose Tissue Immunomodulation: A Novel Therapeutic Approach in Cardiovascular and Metabolic Diseases

AlZaim

Hammoud

Al-Koussa

et al. 2020

Front. Cardiovasc. Med.

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Adipose tissue is a critical regulator of systemic metabolism and bodily homeostasis as it secretes a myriad of adipokines, including inflammatory and anti-inflammatory cytokines. As the main storage pool of lipids, subcutaneous and visceral adipose tissues undergo marked hypertrophy and hyperplasia in response to nutritional excess leading to hypoxia, adipokine dysregulation, and subsequent low-grade inflammation that is characterized by increased infiltration and activation of innate and adaptive immune cells. The specific localization, physiology, susceptibility to inflammation and the heterogeneity of the inflammatory cell population of each adipose depot are unique and thus dictate the possible complications of adipose tissue chronic inflammation. Several lines of evidence link visceral and particularly perivascular, pericardial, and perirenal adipose tissue inflammation to the development of metabolic syndrome, insulin resistance, type 2 diabetes and cardiovascular diseases. In addition to the implication of the immune system in the regulation of adipose tissue function, adipose tissue immune components are pivotal in detrimental or otherwise favorable adipose tissue remodeling and thermogenesis. Adipose tissue resident and infiltrating immune cells undergo metabolic and morphological adaptation based on the systemic energy status and thus a better comprehension of the metabolic regulation of immune cells in adipose tissues is pivotal to address complications of chronic adipose tissue inflammation. In this review, we discuss the role of adipose innate and adaptive immune cells across various physiological and pathophysiological states that pertain to the development or progression of cardiovascular diseases associated with metabolic disorders. Understanding such mechanisms allows for the exploitation of the adipose tissue-immune system crosstalk, exploring how the adipose immune system might be targeted as a strategy to treat cardiovascular derangements associated with metabolic dysfunctions.

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Section: New Avenues For Adipose Tissue Immunomodulation In Metabolicmentioning

confidence: 99%

Adipose Tissue Immunomodulation: A Novel Therapeutic Approach in Cardiovascular and Metabolic Diseases

AlZaim

Hammoud

Al-Koussa

et al. 2020

Front. Cardiovasc. Med.

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“…Thus, we speculate that infection with H. diminuta creates a positive feedback loop whereby bacteria-derived butyrate and host-derived il-10 cooperate to drive the anti-colitic effect: absence of either negates the beneficial effect of infection with the helminth. In accordance, the recruitment of il-10 + regulatory T cells to the lungs of H. polygyrus -infected mice was dependent on ffar3, and H. polygyrus -evoked changes in the gut microbiome that reduced obesity in high-fat diet-fed mice were dependent of signal transducer and activator of transcription (STAT)-6 (i.e., il-4/il-13 signaling) [ 50 ]. These findings combined with the current data illustrate the intertwined nature of the helminth-host-bacteria relationship and the interplay between host immune factors and bacteria-derived molecules in the suppression of disease.…”

Section: Discussionmentioning

confidence: 99%

Cooperation between host immunity and the gut bacteria is essential for helminth-evoked suppression of colitis

Shute

Callejas

et al. 2021

Microbiome

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Background Studies on the inhibition of inflammation by infection with helminth parasites have, until recently, overlooked a key determinant of health: the gut microbiota. Infection with helminths evokes changes in the composition of their host’s microbiota: one outcome of which is an altered metabolome (e.g., levels of short-chain fatty acids (SCFAs)) in the gut lumen. The functional implications of helminth-evoked changes in the enteric microbiome (composition and metabolites) are poorly understood and are explored with respect to controlling enteric inflammation. Methods Antibiotic-treated wild-type, germ-free (GF) and free fatty-acid receptor-2 (ffar2) deficient mice were infected with the tapeworm Hymenolepis diminuta, then challenged with DNBS-colitis and disease severity and gut expression of the il-10 receptor-α and SCFA receptors/transporters assessed 3 days later. Gut bacteria composition was assessed by 16 s rRNA sequencing and SCFAs were measured. Other studies assessed the ability of feces or a bacteria-free fecal filtrate from H. diminuta-infected mice to inhibit colitis. Results Protection against disease by infection with H. diminuta was abrogated by antibiotic treatment and was not observed in GF-mice. Bacterial community profiling revealed an increase in variants belonging to the families Lachnospiraceae and Clostridium cluster XIVa in mice 8 days post-infection with H. diminuta, and the transfer of feces from these mice suppressed DNBS-colitis in GF-mice. Mice treated with a bacteria-free filtrate of feces from H. diminuta-infected mice were protected from DNBS-colitis. Metabolomic analysis revealed increased acetate and butyrate (both or which can reduce colitis) in feces from H. diminuta-infected mice, but not from antibiotic-treated H. diminuta-infected mice. H. diminuta-induced protection against DNBS-colitis was not observed in ffar2−/− mice. Immunologically, anti-il-10 antibodies inhibited the anti-colitic effect of H. diminuta-infection. Analyses of epithelial cell lines, colonoids, and colon segments uncovered reciprocity between butyrate and il-10 in the induction of the il-10-receptor and butyrate transporters. Conclusion Having defined a feed-forward signaling loop between il-10 and butyrate following infection with H. diminuta, this study identifies the gut microbiome as a critical component of the anti-colitic effect of this helminth therapy. We suggest that any intention-to-treat with helminth therapy should be based on the characterization of the patient’s immunological and microbiological response to the helminth.

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“…Six- to eight-week-old female C57BL/6 mice were given 2.5%DSS (w/v) in drinking water for 7 days to induce colitis, then the colitis mice were supplemented with sterile water or QCWZD at 1.8 g/kg in the absence or presence of an antibiotics cocktail (Kanamycin 0.4 mg/ml, Gentamicin 0.035 mg/ml, Metronidazole 0.215 mg/ml, Vancomycin 0.045 mg/ml, Colistin 850 U/mL) ( Su et al, 2020 ) for one week before euthanized with carbon dioxide for colon tissues.…”

Section: Methodsmentioning

confidence: 99%

Qingchang Wenzhong Decoction Accelerates Intestinal Mucosal Healing Through Modulation of Dysregulated Gut Microbiome, Intestinal Barrier and Immune Responses in Mice

Sun

Wang³

et al. 2021

Front. Pharmacol.

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Inflammatory bowel disease (IBD), a group of multifactorial and inflammatory infirmities, is closely associated with dysregulation of gut microbiota and host metabolome, but effective treatments are currently limited. Qingchang Wenzhong Decoction (QCWZD) is an effective and classical traditional herbal prescription for the treatment of IBD and has been proved to attenuate intestinal inflammation in a model of acute colitis. However, the role of QCWZD in recovery phase of colitis is unclear. Here, we demonstrated that mice treated with QCWZD showed a faster recovery from dextran sulfate sodium (DSS)-induced epithelial injury, accompanied by reduced mucosal inflammation and attenuated intestinal dysbiosis using bacterial 16S rRNA amplicon sequencing compared to those receiving sterile water. The protective effects of QCWZD are gut microbiota dependent, as demonstrated by fecal microbiome transplantation and antibiotics treatment. Gut microbes transferred from QCWZD-treated mice displayed a similar role in mucosal protection and epithelial regeneration as QCWZD on colitis in mice, and depletion of the gut microbiota through antibiotics treatments diminished the beneficial effects of QCWZD on colitis mice. Moreover, metabolomic analysis revealed metabolic profiles alternations in response to the gut microbiota reprogrammed by QCWZD intervention, especially enhanced tryptophan metabolism, which may further accelerate intestinal stem cells-mediated epithelial regeneration to protect the integrity of intestinal mucosa through activation of Wnt/β-catenin signals. Collectively, our results suggested that orally administrated QCWZD accelerates intestinal mucosal healing through the modulation of dysregulated gut microbiota and metabolism, thus regulating intestinal stem cells-mediated epithelial proliferation, and hold promise for novel microbial-based therapies in the treatment of IBD.

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

Cited by 34 publications

References 50 publications

Adipose Tissue Immunomodulation: A Novel Therapeutic Approach in Cardiovascular and Metabolic Diseases

Adipose Tissue Immunomodulation: A Novel Therapeutic Approach in Cardiovascular and Metabolic Diseases

Cooperation between host immunity and the gut bacteria is essential for helminth-evoked suppression of colitis

Qingchang Wenzhong Decoction Accelerates Intestinal Mucosal Healing Through Modulation of Dysregulated Gut Microbiome, Intestinal Barrier and Immune Responses in Mice

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