Methods for modulating intestinal microbiota

A mammalian, defensin technology, applied in the field of regulating or stabilizing intestinal microbiota, can solve problems such as metabolic disorders

Inactive Publication Date: 2018-11-09
DEFENSIN THERAPEUTICS APS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Ectopic lipid accumulation (hepatic steatosis and elevated serum triglyceride levels) leading to severe metabolic impairment despite the absence of weight gain (often presenting with a healthy phenotype)

Method used

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  • Methods for modulating intestinal microbiota
  • Methods for modulating intestinal microbiota
  • Methods for modulating intestinal microbiota

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0257] Modulation of gut microbiota and prevention of gut inflammation and metabolic syndrome by prophylactic treatment with defensins.

[0258] Materials and methods

[0259] mouse: Mice were housed in triplicate, 4 cages per group. Feed intake was registered daily before lights were turned off (6pm). The experimental procedure of grouping and order of cage changes was performed for each mouse. Mice were maintained at room temperature on a 12-h light / dark cycle under SPF standard conditions.

[0260] diet: For dosing, the average body weight was estimated to be 25 g per mouse. They ate approximately 3 grams of feed per mouse per day.

[0261] Solution ( Figure 1A ): Mice were fed a high-fat diet (HFD) or a low-fat (LF) control diet. HFD contained 4 subgroups; 1 hBD2, 1 HD5, 1 hBD2 / HD5 and 1 standard HFD without defensin supplementation. The defensin concentration was 1,2 mg hBD2 per kg mouse per day. HD5 was administered at an equimolar concentration with hBD2....

Embodiment 2

[0297] Example 2. Modulation of gut microbiota by defensins.

[0298] Invertebrates: For in vivo proof of concept, the invertebrate greater wax moth model, G. mellonella, can be used. Feces can be analyzed after force feeding administration of α-defensins and / or β-defensins (Giannouli et al. 2014)(Favre-Godal et al. 2014).

Embodiment 3

[0299] Example 3. Modulation of gut microbiota, gut inflammation and metabolic syndrome parameters by intervention treatment with defensins in obese mice.

[0300] Mice and diet. This experiment elucidates the role of hBD-2 and HD5 in the treatment of metabolic syndrome (MetS) in diet-induced obese mice. The intervention was preceded by a 13-week run-in period in which mice were fed a very HFD (60% energy from fat). Only mice meeting the minimum 12 gram weight gain criterion (approximately 50% of initial body weight) during the run-in period were included in the final analysis. Mice that did not meet these criteria were kept in their respective cages as hierarchical "guardians". They were exposed to all experimental tests but excluded from analysis.

[0301] Solution ( Figure 1B ). Before the intervention, all mice underwent MR scans and underwent OGTT. Cages of mice were assigned to experimental groups based on their fat mass. All subsequent measures were paired wit...

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Abstract

The present invention relates to methods for modulating the intestinal microbiota by administering one or more defensins and / or GLP-1 / GLP-1 analogs and methods for prevention or treatment of gut inflammation by oral administration of one or more defensins. GLP-1 analogs such as Liraglutide, as well as mammalian and poultry alfa and beta defensins can cause a change in the composition of the microbiota and metabolome in the intestine and can therefore be used to treat or prevent gut inflammation, colorectal cancer, metabolic syndrome, obesity, prediabetes and diabetes or as lean growth promoters in the meat production.

Description

technical field [0001] The present invention relates to methods of modulating or stabilizing the gut microbiota by orally administering one or more defensins. The method can be used to treat or prevent intestinal inflammation, colorectal cancer, metabolic syndrome, obesity, prediabetes, diabetes and cardiovascular disease as well as to promote lean growth in meat production. Background of the invention [0002] gut microbiota [0003] The increasing prevalence of common disorders such as obesity and obesity-related diseases is closely related to our Westernized lifestyles and diets. The most prominent obesity-related diseases are insulin resistance, overt type 2 diabetes (T2D), and certain cancers (Faulds & Dahlman-Wright, 2012). Although the etiology of these diseases is complex, many of them are characterized by a general state of low-grade inflammation, which may stem from gut microbiota dysbiosis (Everard & Cani, 2013; Belkaid & Hand, 2014). Although the challenges a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/00A61K38/17C07K14/47A23L33/00
CPCA61K38/26A61K38/28C07K14/605C07K14/4723A23L33/30A61K38/1729A61P1/14A61P3/00A61P3/04A61P3/10A61K2300/00A61P1/00A61K9/0053A61K31/155A61K45/06C07K14/765C07K2319/31
Inventor P·诺德吉尔德J·韦卡普S·卡路福
Owner DEFENSIN THERAPEUTICS APS
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