Matthew Snelson

• Monash University (Australia)

The formation of advanced glycation end products (AGEs) in foods is accelerated with heat treatment, particularly within foods that are cooked at high temperatures for long periods of time using dry heat. The modern processed diet is replete with AGEs, and excessive AGE consumption is thought to be associated with a number of negative health effect...

Chronic kidney disease (CKD) has been associated with changes in gut microbial ecology, or “dysbiosis,” which may contribute to disease progression. Recent studies have focused on dietary approaches to favorably alter the composition of the gut microbial communities as a treatment method in CKD. Resistant starch (RS), a prebiotic that promotes prol...

Diet is one of the largest modifiable risk factors for chronic kidney disease (CKD)-related death and disability. CKD is largely a progressive disease; however, it is increasingly appreciated that hallmarks of chronic kidney disease such as albuminuria can regress over time. The factors driving albuminuria resolution remain elusive. Since albuminur...

The sequelae of diabetes mellitus include microvascular complications such as diabetic kidney disease (DKD), which involves glucose-mediated renal injury that is associated with a disruption in mitochondrial metabolic agility, inflammation and fibrosis. We explored the role of the innate immune complement component C5a, a potent mediator of inflamm...

Published evidence exploring the effects of dietary resistant starch (RS) on human cardiometabolic health is inconsistent. This review aimed to investigate the effect of dietary RS type 2 (RS2) supplementation on body weight, satiety ratings, fasting plasma glucose, glycated hemoglobin (HbA1c), insulin resistance and lipid levels in healthy individ...

The gastrointestinal (GI) tract plays a critical role in nutrition and the pathophysiology of disease, and there is an increasing variety of methodologies available for the assessment of various aspects of GI physiology. Advancements in assessment methods, including techniques to study gut motility, fermentation, permeability, and microbiota compos...

Background: Gut microbial metabolites called short-chain fatty acids (SCFA) confer protective effects against cardiovascular disease and high blood pressure. Proposed mechanisms include anti-inflammatory signalling mediated by SCFA-sensing G-protein-coupled receptors (GPCR), particularly GPR41, GPR43, and GPR109a, as suggested by knockout mouse mod...

Background/Objective Dietary interventions high in fibre have been shown to lower blood pressure (BP). This effect is via the gut microbiota, via fermentation of fibre and production of metabolites called short-chain fatty acids (SCFAs). Not all patients respond to dietary fibre interventions for unclear reasons. We aimed to determine if we can ide...

Background Dietary-resistant starch is emerging as a potential therapeutic tool to limit the negative effects of diabetes on the kidneys. However, its metabolic and immunomodulatory effects have not yet been fully elucidated. Methods Six-week-old db/db mice were fed a diet containing 12.5% resistant starch or a control diet matched for equivalent...

The gut microbiota and short chain fatty acids (SCFA) have been associated with immune regulation and autoimmune diseases. Autoimmune kidney diseases arise from a loss of tolerance to antigens, often with unclear triggers. In this review, we explore the role of the gut microbiome and how disease, diet, and therapy can alter the gut microbiota conso...

Purpose of the Review To review what intestinal permeability is and how it is measured, and to summarise the current evidence linking altered intestinal permeability with the development of hypertension. Recent Findings Increased gastrointestinal permeability, directly measured in vivo, has been demonstrated in experimental and genetic animal mode...

According to several international, regional, and national guidelines on hypertension, lifestyle interventions are the first-line treatment to lower blood pressure (BP). Although diet is one of the major lifestyle modifications described in hypertension guidelines, dietary fiber is not specified. Suboptimal intake of foods high in fiber, such as in...

Autoimmune kidney diseases arise from a loss of tolerance to antigens, often with unclear triggers. In this review we explore the role of the gut microbiome and how disease, diet and therapy can alter the gut microbiota consortium. Perturbations in the gut microbiota may induce the translocation of microbiota-derived inflammatory molecules such as...

Changes in mitochondrial energy metabolism are thought to be central to the development of diabetic kidney disease (DKD); however, whether this response is explicitly driven by systemic glucose concentrations remains unknown. Here, we show that titrating blood glucose concentrations in vivo directly impacts mitochondrial morphology and bioenergetic...

Gut microbiome research has increased dramatically in the last decade, including in renal health and disease. The field is moving from experiments showing mere association to causation using both forward and reverse microbiome approaches, leveraging tools such as germ-free animals, treatment with antibiotics, and faecal microbiota transplantations....

Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a rare autoimmune disease with suboptimal treatment options which contribute to morbidity and mortality. The characteristic pathological feature is severe inflammation induced by neutrophils which causes life threatening damage to the small blood vessels of the kidney. Neutr...

Introduction Gut microbiome studies often overlook experimental factors that could influence gut microbiome diversity and could impact findings. Large-scale studies investigating these experimental factors are lacking. Thus, we aimed to determine which experimental factors influence the gut microbiome diversity in pre-clinical animal model studies....

Diabetes is the leading cause of kidney disease, and as the number of individuals with diabetes increases there is a concomitant increase in the prevalence of diabetic kidney disease (DKD). Diabetes contributes to the development of DKD through a number of pathways, including inflammation, oxidative stress, and the gut-kidney axis, which may be ame...

A recently published study by Bell et al. shows altered immunotolerance in people with type 1 diabetes by dietary supplementation of modified resistant starch fibre.

High-heat processed foods contain proteins that are partially resistant to enzymatic digestion and pass through to the colon. The fermentation of resistant proteins by gut microbes produces products that may contribute to chronic disease risk. This pilot study examined the effects of a resistant protein diet on growth, fecal microbiome, protein fer...

There is increasing evidence for the role of intestinal permeability as a contributing factor in the pathogenesis of diabetes; however, the molecular mechanisms are poorly understood. Advanced glycation endproducts, of both exogenous and endogenous origin, have been shown to play a role in diabetes pathophysiology, in part by their ligation to the...

Synbiotics have emerged as a therapeutic strategy for modulating the gut microbiome and targeting novel cardiovascular risk factors, including uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (PCS). This study aims to evaluate the feasibility of a trial of long-term synbiotic supplementation in adults with stage 3–4 chronic kidney disease (C...

Significance The metabolic disorder, diabetes mellitus, results in microvascular complications, including diabetic kidney disease (DKD), which is partly believe to involve disrupted energy generation in the kidney, leading to injury that is characterized by inflammation and fibrosis. An increasing body of evidence indicates that the innate immune c...

Objective This study aims to explore the associations between diet quality, uraemic toxins, and gastrointestinal microbiota in the chronic kidney disease (CKD) population. Methods This is a baseline cross-sectional study of adults with CKD participating in a randomized controlled trial of prebiotic and probiotic supplementation. Dietary intake was...

Background/Objectives: Faecal microbiota transplant (FMT) is a powerful tool used to connect changes in gut microbial composition with a variety of disease states and pathologies. While FMT enables potential causal relationships to be identified, the experimental details reported in preclinical FMT protocols are highly inconsistent and/or incomplet...

Objectives The primary objective of this study was to ascertain whether thermally processed diets influence albuminuria and intestinal permeability via alterations in the complement cascade. A secondary objective was to see whether these pathological alterations could be ameliorated by a gut-targeted dietary intervention, resistant starch. Methods...

Background and Aims Individuals with chronic kidney disease (CKD) have significantly increased risk of cardiovascular mortality which is only partially explained by Framingham risk factors. There is a growing body of evidence linking the gut-derived uraemic toxins indoxyl sulphate (IS) and p-cresyl sulphate (PCS) with accelerated kidney disease pro...

Background and Aims Synbiotics, co-administered prebiotics and probiotics, have emerged over the last decade as an innocuous intervention targeting the microbial generation of the uraemic toxins, indoxyl sulphate (IS) and p-cresyl sulphate (PCS). However, most trials to date are of short duration (2-24 weeks). In order to inform translation into cl...

Diabetic kidney disease (DKD) remains the number one cause of end-stage renal disease in the western world. In experimental diabetes, mitochondrial dysfunction in the kidney precedes the development of DKD. Reactive 1,2-dicarbonyl compounds, such as methylglyoxal, are generated from sugars both endogenously during diabetes and exogenously during fo...

Intake of processed foods has increased markedly over the past decades, coinciding with increased microvascular diseases such as chronic kidney disease (CKD) and diabetes. Here, we show in rodent models that long-term consumption of a processed diet drives intestinal barrier permeability and an increased risk of CKD. Inhibition of the advanced glyc...

Scope This study evaluated the effects of a chronic high protein diet (HPD) on kidney injury, intestinal permeability and gut microbiota perturbations in a mouse model. Method and results Mice were fed a diet containing either 20% or 52% energy from protein for 24 weeks; protein displaced an equivalent amount of wheat starch. The HPD did not alter...

Diabetes is a metabolic condition. The composition of the gut microbiota is altered in diabetes with reduced levels of short chain fatty acids (SCFA) producers, notably butyrate. Butyrate is associated with a number of beneficial effects including promoting the integrity of the gastrointestinal barrier. Diabetes may lead to an increase in the perme...

Fecal microbiota transplant (FMT) is a powerful tool used to connect changes in gut microbial composition with a variety of disease states and pathologies. While FMT enables potential causal relationships to be identified, the experimental details reported in preclinical FMT protocols are highly inconsistent and/or incomplete. This limitation refle...

Background The NADPH oxidase isoform, Nox4, mediates reactive oxygen species (ROS) production and renal fibrosis in diabetic kidney disease at the level of the podocyte. However, the mitochondrial localization of Nox4 and its role as a mitochondrial bioenergetic sensor has recently been reported. Whether Nox4 drives pathology in diabetic kidney dis...

There is increasing evidence of the influence of the gut microbiota on hypertension and its complications, such as chronic kidney disease, stroke, heart failure, and myocardial infarction. This is not surprising considering that the most common risk factors for hypertension, such as age, sex, medication, and diet, can also impact the gut microbiota...

Background: High blood pressure (BP) continues to be a major, poorly controlled but modifiable risk factor for cardiovascular death. Amongst key Western lifestyle factors, a diet poor in fibre is associated with prevalence of high BP. The impact of lack of prebiotic fibre and the associated mechanisms that lead to higher BP are unknown. Here we sho...

Alterations in gut homeostasis may contribute to the progression of diabetic nephropathy. There has been recent attention on the renoprotective effects of metabolite-sensing receptors in chronic renal injury, including the G-protein-coupled-receptor (GPR)109a, which ligates the short chain fatty acid butyrate. However, the role of GPR109a in the de...

Mitochondrial stress has been widely observed in Diabetic Kidney Disease (DKD). Cyclophilin D (CypD) is a functional component of the mitochondrial permeability transition pore (mPTP) which allows the exchange of ions and solutes between the mitochondrial matrix to induce mitochondrial swelling and activation of cell death pathways. CypD has been s...

It is increasingly recognized that the gut microbiota plays a role in the progression of chronic diseases and that diet may confer health benefits by altering the gut microbiota composition. This is of particular relevance for chronic kidney disease (CKD), as the gut is a source of uremic retention solutes, which accumulate as a result of impaired...

Background: High fibre intake is associated with lower blood pressure (BP) in epidemiological and clinical studies. Prebiotic fibre resists digestion in the upper gastrointestinal tract and is fermented by gut microbiota in the intestine. The impact of lack of prebiotic dietary fibre in BP remains unknown. Objectives: To determine the consequences...

BACKGROUND: Alterations in gut homeostasis may contribute to the progression of diabetic nephropathy (DN). Resistant starch (RS) is a prebiotic fibre that promotes the production of butyrate by the gut microbiota. Butyrate acts as a ligand for G-protein-coupled-receptor (GPR)190a, decreasing intestinal inflammation and promoting gut epithelial barr...

A number of studies report that a diet high in protein influences cognitive performance, but the results are inconsistent. Studies demonstrated that protein from different food sources has differential effects on cognition. It is increasingly recognized that the integrity of cerebrovascular blood–brain barrier (BBB) is pivotal for central nervous s...