Oral Bifidobacterium longum expressing GLP-2 improves nutrient assimilation and nutritional homeostasis in mice

Zhang, Qian; Liu, Mengge; Li, Shiyu; Xu, Zhenrui; Wang, Jiajia; Wang, Yuzhe; Fei, Zhengbin; Huang, Wenhua; Sun, Han

doi:10.1016/j.mimet.2018.01.002

Cited by 8 publications

(6 citation statements)

References 35 publications

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“…Today, only few strains of bifidobacteria have been proposed as live delivery vehicles. For instance, some strains of B. longum have been used as a delivery vector for the development of: (i) oral vaccine against Hepatitis C virus (HVC) and Enterovirus 71 (Yu et al, 2013; Takei et al, 2014), (ii) anti-tumoral treatment (Shirakawa and Kitagawa, 2017), and (iii) to treat metabolic disorders in mice (Zhang et al, 2018). Other reports have described the use of genetically modified bifidobacteria to express diverse heterologous proteins (Khokhlova et al, 2010; Losurdo et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

A New Bifidobacteria Expression SysTem (BEST) to Produce and Deliver Interleukin-10 in Bifidobacterium bifidum

et al. 2018

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In the last years there has been a growing interest in the use of genetically modified bacteria to deliver molecules of therapeutic interest at mucosal surfaces. Due to the well-recognized probiotic properties of some strains, bifidobacteria represent excellent candidates for the development of live vehicles to produce and deliver heterologous proteins at mucosal surfaces. However, very few studies have considered this genus because of its complexity to be genetically manipulated. In this work, we report the development of a new Bifidobacteria Expression SysTem (BEST) allowing the production of heterologous proteins in Bifidobacterium bifidum. This system is based on: i) the broad host range plasmid pWV01, ii) a stress-inducible promoter, and iii) two different signal peptides (SPs) one issued from Lactococcus lactis (SPExp4) and issued from Bifidobacterium longum (SPBL1181). The functionality of BEST system was validated by cloning murine interleukin-10 (IL-10) and establishing the resulting plasmids (i.e., pBESTExp4:IL-10 and pBESTBL1181:IL-10) in the strain of B. bifidum BS42. We then demonstrated in vitro that recombinant B. bifidum BS42 harboring pBESTBL1181:IL-10 plasmid efficiently secreted IL-10 and that this secretion was significantly higher (sevenfold) than its counterpart B. bifidum BS42 harboring pBESTExp4:IL-10 plasmid. Finally, we validated in vivo that recombinant B. bifidum strains producing IL-10 using BEST system efficiently delivered this cytokine at mucosal surfaces and exhibit beneficial effects in a murine model of low-grade intestinal inflammation.

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Section: Introductionmentioning

confidence: 99%

A New Bifidobacteria Expression SysTem (BEST) to Produce and Deliver Interleukin-10 in Bifidobacterium bifidum

et al. 2018

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“…Based on early data from animal models, GLP-2 was considered a promising therapeutic target for inflammatory and short bowel syndromes [ 59 , 92 ] because of its anti-apoptotic and proliferative activity on intestinal epithelium [ 56 , 64 ]. In line with these observations, GLP-2 has been shown to enhance intestinal blood flow [ 93 ] and increase surface area for absorption through increased crypt cell proliferation, intestine weight and length [ 94 ] while suppressing intestinal permeability [ 95 , 96 ]. Eventually, a stable analogue of GLP-2, teduglutide, has been approved to reduce parenteral support for patients with short bowel syndrome which is a life-threatening condition resulting from surgical removal of a significant mass of functional small intestine in patients with Crohn’s disease [ 2 , 97 , 98 ].…”

Section: Glp-1 and Glp-2 As Regulators Of Intestine Integrity And Inf...mentioning

confidence: 94%

“…Interestingly, these effects were GLP-2 dependent [ 207 ]. Another study in diet-induced obese rats showed that probiotic Bifidobacterium animalis elevated GLP-2 levels [ 95 ]. Moreover, in patients with ulcerative colitis, serum level of GLP-2 was associated with microbiota diversity and abundance [ 208 ].…”

Section: Glp-1 and Glp-2 Mediate Gut Microbiota–immune System Crosstalkmentioning

confidence: 99%

GLP-1 and GLP-2 Orchestrate Intestine Integrity, Gut Microbiota, and Immune System Crosstalk

Abdalqadir

Adeli

2022

Microorganisms

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The intestine represents the body’s largest interface between internal organs and external environments except for its nutrient and fluid absorption functions. It has the ability to sense numerous endogenous and exogenous signals from both apical and basolateral surfaces and respond through endocrine and neuronal signaling to maintain metabolic homeostasis and energy expenditure. The intestine also harbours the largest population of microbes that interact with the host to maintain human health and diseases. Furthermore, the gut is known as the largest endocrine gland, secreting over 100 peptides and other molecules that act as signaling molecules to regulate human nutrition and physiology. Among these gut-derived hormones, glucagon-like peptide 1 (GLP-1) and -2 have received the most attention due to their critical role in intestinal function and food absorption as well as their application as key drug targets. In this review, we highlight the current state of the literature that has brought into light the importance of GLP-1 and GLP-2 in orchestrating intestine–microbiota–immune system crosstalk to maintain intestinal barrier integrity, inflammation, and metabolic homeostasis.

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“…Moreover, data show that MAP, EGFR/TyrK pathways are involved (Martin et al 2006). It is also known as a GI growth factor: it increases intestinal blood flow (Mayo et al 2017), increases absorption (Feng et al 2017), proliferation, decreases apoptosis (Li et al 2016) and reduces intestinal permeability (Zhang et al 2018), and suppresses gastric secretion and motility. Recent data demonstrated that exogenous administration of GLP-2 correlates with increase in total gut weight, length, villus height, crypt depth, and crypt cell proliferation (Gu et al 2018).…”

Section: Glucagon-like Peptidesmentioning

confidence: 99%

Role of glucagon-like peptides in inflammatory bowel diseases—current knowledge and future perspectives

Zatorski

Sałaga

Fichna

2019

Naunyn-Schmiedeberg's Arch Pharmacol

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Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic, relapsing, intestinal inflammatory disorders with complex and yet unrevealed pathogenesis in which genetic, immunological, and environmental factors play a role. Nowadays, a higher proportion of elderly IBD patients with coexisting conditions, such as cardiovascular disease and/or diabetes is recorded, who require more complex treatment and became a great challenge for gastroenterologists. Furthermore, some patients do not respond to anti-IBD therapy. These facts, together with increasing comorbidities in patients with IBD, imply that urgent, more complex, novel therapeutic strategies in the treatment are needed. Glucagon-like peptides (GLPs) possess numerous functions in the human body such as lowering blood glucose level, controlling body weight, inhibiting gastric emptying, reducing food ingestion, increasing crypt cell proliferation, and improving intestinal growth and nutrient absorption. Thus, GLPs and dipeptidyl peptidase IV (DPP-IV) inhibitors have recently gained attention in IBD research. Several animal models showed that treatment with GLPs may lead to improvement of colitis. This review presents data on the multitude effects of GLPs in the inflammatory intestinal diseases and summarizes the current knowledge on GLPs, which have the potential to become a novel therapeutic option in IBD therapy.

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Oral Bifidobacterium longum expressing GLP-2 improves nutrient assimilation and nutritional homeostasis in mice

Cited by 8 publications

References 35 publications

A New Bifidobacteria Expression SysTem (BEST) to Produce and Deliver Interleukin-10 in Bifidobacterium bifidum

A New Bifidobacteria Expression SysTem (BEST) to Produce and Deliver Interleukin-10 in Bifidobacterium bifidum

GLP-1 and GLP-2 Orchestrate Intestine Integrity, Gut Microbiota, and Immune System Crosstalk

Role of glucagon-like peptides in inflammatory bowel diseases—current knowledge and future perspectives

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