HMOs for Gut Microbiome and Inflammation in Renal Disease

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Solution Overview

Problem

Constipation in patients with renal disease, particularly those with end-stage renal disease (ESRD), exacerbates gut-derived toxins and inflammation, increasing cardiovascular disease risk and complicating dialysis, especially peritoneal dialysis, due to altered gut microbiome and mechanical effects.

Innovation Solution

Administering effective amounts of human milk oligosaccharides (HMOs), such as 2′-fucosyllactose (2′-FL), to improve bowel movement consistency, reduce inflammation, and enhance gut microbiome health, thereby addressing constipation and related complications in renal disease patients.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional treatments for constipation are used in renal disease patients, then bowel movement frequency may improve, but gut microbiome alteration and inflammation persist

Engineering Contradiction:
Improvebowel movement frequencyVSAvoidgut-derived toxins and inflammation
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces prebiotic compounds (oligosaccharides, inulin, FOS, GOS) as intermediary substances that selectively stimulate growth of beneficial gut bacteria (Bifidobacterium, Lactobacillus). These prebiotics act as mediators between the administered substance and the gut microbiome, promoting production of short-chain fatty acids that reduce inflammation and gut-derived toxins without directly stimulating bowel movements, thereby addressing both constipation and inflammatory markers simultaneously

Inventive Principle:
Principle #24Intermediary (Mediator)

2Stability of the object's composition

If phosphate binders and other medications are administered to renal disease patients, then mineral balance improves, but constipation worsens

Engineering Contradiction:
Improvemineral balanceVSAvoidbowel function
Core Design Contradiction:
Stability of the object's compositionVSEase of operation

Solution Approach 1:

The patent converts the harmful side effect of phosphate binder-induced constipation into a beneficial outcome by administering prebiotics that selectively promote beneficial gut bacteria. These bacteria produce short-chain fatty acids that improve mineral absorption and reduce inflammation, thereby converting the medication-induced harm (constipation) into a benefit (improved gut health and mineral balance)

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

3Object-generated harmful factors

If dialysis treatment is intensified to remove toxins, then blood toxin levels decrease, but gut microbiome damage and intestinal barrier dysfunction increase

Engineering Contradiction:
Improveblood toxin levelsVSAvoidintestinal barrier function
Core Design Contradiction:
Object-generated harmful factorsVSReliability

Solution Approach 1:

The patent applies preliminary action by administering prebiotics before significant gut microbiome damage occurs or alongside dialysis treatment. The prebiotics proactively cultivate beneficial bacteria that produce short-chain fatty acids, which strengthen the intestinal barrier and reduce inflammation in advance, preventing the progressive damage that would otherwise occur with intensive dialysis treatment

Inventive Principle:
Principle #10Preliminary action

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The administration of HMOs, particularly 2′-FL, improves bowel regularity, reduces serum inflammatory markers, enhances nutrition, and decreases the risk of peritonitis by promoting a healthier gut microbiome and intestinal barrier function, benefiting patients with chronic kidney disease and those on dialysis.

Implementation Method 1

HMOs have long been known to be fermented by bacteria in the colon to produce short chain fatty acids

Methodology Applied
Scientific EffectFermentation: Fermentation

Implementation Method 2

HMOs have been shown to selectively stimulate the growth and activity of beneficial bacteria such as Bifidobacterium and Lactobacillus

Methodology Applied
Scientific EffectSelective stimulation of bacterial growth:

Data Source

PatentUS11712445B2Compositions and methods for improving gastrointestinal function in subjects with renal disease
Publication Date: 2023.08.01 KHARAIT SOURABH

AI summary

The present disclosure relates generally to compositions and methods for improving the consistency and regularity of a subject's bowel movements. Additionally, the compositions and methods are useful for also improving deficiencies in nutrition, deficiencies in hemoglobin, and reducing inflammation.