Effect of Aging and Glucagon-like Peptide 2 on Intestinal Microbiota in SD Rats

Wu, Jiayu; Ren, Weiying; Li, Li; Luo, Man; Xu, Kan; Shen, Jiping; Jia, Wang; Chang, Guilin; Lü, Yi; Qi, Yihong; Xu, Borui; He, Yuting; Hu, Yu

doi:10.14336/ad.2017.1001

Cited by 14 publications

(12 citation statements)

References 24 publications

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“…Knowledge in this area is still sparse as structural modulation of the gut microbiome has only been reported at a relative low level of resolution (phylum/genus level) following treatment with agonists selective for the GLP-1 31–34 and GLP-2 25,35 receptors. In addition, most current approaches for analyzing gut microbiome data rely on comparisons to reference genomes 36 .…”

Section: Introductionmentioning

confidence: 99%

Metabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice

Madsen

Holm

Pallejà

et al. 2019

Sci Rep

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Enteroendocrine L-cell derived peptide hormones, notably glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2), have become important targets in the treatment of type 2 diabetes, obesity and intestinal diseases. As gut microbial imbalances and maladaptive host responses have been implicated in the pathology of obesity and diabetes, this study aimed to determine the effects of pharmacologically stimulated GLP-1 and GLP-2 receptor function on the gut microbiome composition in diet-induced obese (DIO) mice. DIO mice received treatment with a selective GLP-1 receptor agonist (liraglutide, 0.2 mg/kg, BID) or dual GLP-1/GLP-2 receptor agonist (GUB09–145, 0.04 mg/kg, BID) for 4 weeks. Both compounds suppressed caloric intake, promoted a marked weight loss, improved glucose tolerance and reduced plasma cholesterol levels. 16S rDNA sequencing and deep-sequencing shotgun metagenomics was applied for comprehensive within-subject profiling of changes in gut microbiome signatures. Compared to baseline, DIO mice assumed phylogenetically similar gut bacterial compositional changes following liraglutide and GUB09-145 treatment, characterized by discrete shifts in low-abundant species and related bacterial metabolic pathways. The microbiome alterations may potentially associate to the converging biological actions of GLP-1 and GLP-2 receptor signaling on caloric intake, glucose metabolism and lipid handling.

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Section: Introductionmentioning

confidence: 99%

Metabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice

Madsen

Holm

Pallejà

et al. 2019

Sci Rep

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“…However, whether GLP-2 could ameliorate the intestinal microbiota dysbiosis of SBS has not been studied. Yu Hu and colleagues [ 13 ] demonstrated that GLP-2 treatment resulted in the increase of several probiotics and the decrease of some pathogenic bacterial genera in intestine of aged rats. Therefore, we performed this study to investigate the colonic microbiota of SBS rats with or without GLP-2 intervention.…”

Section: Discussionmentioning

confidence: 99%

“…However, a previous study had found that several days of antibiotics may lead to a reduction of potentially anti-inflammatory Clostridia and an increase of pro-inflammatory Proteobacteria [ 4 ]. According to previous studies, GLP-2 may alleviate intestinal microbiota dysbiosis [ 13 ]. As we expected, GLP-2 treatment significantly downregulated the relative abundance of pro-inflammatory Proteus genus in SBS rats, and increased the relative abundance of potentially anti-inflammatory inhibitory Clostridium genus from Clostridia class in SBS rats.…”

Section: Discussionmentioning

confidence: 99%

“…Our recent study published in Theranostics further demonstrated that GLP-2 exerted its gut mucosal hyperplasia promoting effect through modulating exosomal miRNAs transportation in small intestinal microenvironment [ 1 ]. Moreover, Yu Hu et al [ 13 ] declared that GLP-2 significantly alleviated intestinal flora dysbiosis in elderly rats. However, it remains unknown whether GLP-2 could modulate the intestinal bacterial and fungal dysbiosis in SBS.…”

Section: Introductionmentioning

confidence: 99%

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Therapeutic potential of an intestinotrophic hormone, glucagon-like peptide 2, for treatment of type 2 short bowel syndrome rats with intestinal bacterial and fungal dysbiosis

Cheng

Fan

et al. 2021

BMC Infect Dis

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Background Previous studies showed that type 2 short bowel syndrome (SBS) rats were accompanied by severe intestinal bacterial dysbiosis. Limited data are available for intestinal fungal dysbiosis. Moreover, no effective therapeutic drugs are available for these microbiota dysbiosis. The aims of our study were to investigate the therapeutic potential of glucagon-like peptide 2 (GLP-2) for these microbiota dysbiosis in type 2 SBS rats. Methods 8-week-old male SD rats which underwent 80% small bowel resection, ileocecum resection, partial colon resection and jejunocolostomy, were treated with saline (SBS group, n = 5) or GLP-2 (GLP2.SBS group, n = 5). The Sham group rats which underwent transection and re-anastomosis were given a saline placebo (Sham group, n = 5). 16S rRNA and ITS sequencing were applied to evaluate the colonic bacterial and fungal composition at 22 days after surgery, respectively. Results The relative abundance of Actinobacteria, Firmicutes and proinflammatory Proteobacteria increased significantly in SBS group rats, while the relative abundance of Bacteroidetes, Verrucomicrobia and Tenericutes decreased remarkably. GLP-2 treatment significantly decreased Proteus and increased Clostridium relative to the saline treated SBS rats. The diversity of intestinal fungi was significantly increased in SBS rats, accompanied with some fungi abnormally increased and some resident fungi (e.g., Penicillium) significantly decreased. GLP-2 treatment significantly decreased Debaryomyces and Meyerozyma, and increased Penicillium. Moreover, GLP-2 partially restored the bacteria-fungi interkingdom interaction network of SBS rats. Conclusion Our study confirms the bacterial and fungal dysbiosis in type 2 SBS rats, and GLP-2 partially ameliorated these microbiota dysbiosis.

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“…Aside from GLP-1 secretion, L cells sense pathogen-derived molecules, likely suggesting that GLP-1 functions as an AMP (Greiner and Bäckhed, 2016; Lebrun et al, 2017). Aging has been associated with decreased number of L cells, accounting for the loss of GI tract immunological tolerance (Drozdowski and Thomson, 2006; Wu et al, 2018). Aside from L cells, GALT dysfunction may be linked to the loss of membranous (M) cells, known for producing secretory immunoglobulin A (SIgA), an IEC immune protector (Mantis et al, 2011; Kobayashi et al, 2013; Sato S. et al, 2014; Ohno, 2016).…”

Section: Beta Amyloid: Friend or Foe?mentioning

confidence: 99%

The Post-amyloid Era in Alzheimer's Disease: Trust Your Gut Feeling

Osorio

Kanukuntla

Diaz

et al. 2019

Front. Aging Neurosci.

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The amyloid hypothesis, the assumption that beta-amyloid toxicity is the primary cause of neuronal and synaptic loss, has been the mainstream research concept in Alzheimer's disease for the past two decades. Currently, this model is quietly being replaced by a more holistic, “systemic disease” paradigm which, like the aging process, affects multiple body tissues and organs, including the gut microbiota. It is well-established that inflammation is a hallmark of cellular senescence; however, the infection-senescence link has been less explored. Microbiota-induced senescence is a gradually emerging concept promoted by the discovery of pathogens and their products in Alzheimer's disease brains associated with senescent neurons, glia, and endothelial cells. Infectious agents have previously been associated with Alzheimer's disease, but the cause vs. effect issue could not be resolved. A recent study may have settled this debate as it shows that gingipain, a Porphyromonas gingivalis toxin, can be detected not only in Alzheimer's disease but also in the brains of older individuals deceased prior to developing the illness. In this review, we take the position that gut and other microbes from the body periphery reach the brain by triggering intestinal and blood-brain barrier senescence and disruption. We also surmise that novel Alzheimer's disease findings, including neuronal somatic mosaicism, iron dyshomeostasis, aggressive glial phenotypes, and loss of aerobic glycolysis, can be explained by the infection-senescence model. In addition, we discuss potential cellular senescence targets and therapeutic strategies, including iron chelators, inflammasome inhibitors, senolytic antibiotics, mitophagy inducers, and epigenetic metabolic reprograming.

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Effect of Aging and Glucagon-like Peptide 2 on Intestinal Microbiota in SD Rats

Cited by 14 publications

References 24 publications

Metabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice

Metabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice

Therapeutic potential of an intestinotrophic hormone, glucagon-like peptide 2, for treatment of type 2 short bowel syndrome rats with intestinal bacterial and fungal dysbiosis

The Post-amyloid Era in Alzheimer's Disease: Trust Your Gut Feeling

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