scholarly journals Impact of altering gut microbiota metabolism on osteomyelitis severity in obesity-related type 2 diabetes

2022 ◽  
Author(s):  
Tina I Bui ◽  
Ann Lindley Gill ◽  
Robert A Mooney ◽  
Steven R Gill

Staphylococcus aureus is an opportunistic pathogen causing osteomyelitis through hematogenous seeding or contamination of implants and open wounds following orthopedic surgeries. The severity of S. aureus-mediated osteomyelitis is enhanced in obesity-related type 2 diabetes (obesity/T2D) due to chronic inflammation impairing both adaptive and innate immunity. Obesity-induced inflammation is linked to gut dysbiosis, with modification of the gut microbiota by high-fiber diets leading to a reduction in the symptoms and complications of obesity/T2D. However, our understanding of the mechanisms by which modifications of the gut microbiota alter host infection responses is limited. To address this gap, we monitored tibial S. aureus infections in obese/T2D mice treated with the inulin-like fructan fiber, oligofructose. Treatment with oligofructose significantly decreased S. aureus colonization and lowered proinflammatory signaling post-infection in obese/T2D mice, as observed by decreased circulating inflammatory cytokines (TNF-α) and chemokines (IP-10, KC, MIG, MCP-1, and RANTES), indicating partial reduction in inflammation. Oligofructose markedly shifted diversity in the gut microbiota of obese/T2D mice mice, with notable increases in the anti-inflammatory bacterium, Bifidobacterium pseudolongum. Analysis of the cecum and plasma metabolome suggested polyamine production was increased, specifically spermine and spermidine. Oral administration of these polyamines to obese/T2D mice resulted in reduced infection severity similar to oligofructose supplementation, suggesting polyamines can mediate the beneficial effects of fiber on osteomyelitis severity. These results demonstrate the contribution of gut microbiota metabolites to the control of bacterial infections distal to the gut and polyamines as an adjunct therapeutic for osteomyelitis in obesity/T2D.

2020 ◽  
Vol 11 (7) ◽  
pp. 5749-5767
Author(s):  
Huicui Liu ◽  
Min Zhang ◽  
Qingyu Ma ◽  
Baoming Tian ◽  
Chenxi Nie ◽  
...  

Resistant starch (RS) is well known to prevent type 2 diabetes mellitus (T2DM) and obesity.


2019 ◽  
Author(s):  
Torben Sølbeck Rasmussen ◽  
Caroline M. Junker Mentzel ◽  
Witold Kot ◽  
Josué L. Castro-Mejía ◽  
Simone Zuffa ◽  
...  

ABSTRACTObjectiveDevelopment of obesity and type-2-diabetes (T2D) are associated with gut microbiota (GM) changes. The gut viral community is predominated by bacteriophages (phages), which are viruses that attack bacteria in a host-specific manner. As a proof-of-concept we demonstrate the efficacy of faecal virome transplantation (FVT) from lean donors for shifting the phenotype of obese mice into closer resemblance of lean mice.DesignThe FVT consisted of viromes extracted from the caecal content of mice fed a low-fat (LF) diet for fourteen weeks. Male C57BL/6NTac mice were divided into five groups: LF (as control), high-fat diet (HF), HF+Ampicillin (Amp), HF+Amp+FVT and HF+FVT. At week six and seven of the study the HF+FVT and HF+Amp+FVT mice were treated with FVT by oral gavage. The Amp groups were treated with ampicillin 24 h prior to first FVT treatment.ResultsSix weeks after first FVT the HF+FVT mice showed a significant decrease in weight gain compared to the HF group. Further, glucose tolerance was comparable between the lean LF and HF+FVT mice, while the other HF groups all had impaired glucose tolerance. These observations were supported by significant shifts in GM composition, blood plasma metabolome, and expression levels of genes involved in obesity and T2D development.ConclusionsTransfer of gut viral communities from mice with a lean phenotype into those with an obese phenotype reduce weight gain and normalise blood glucose parameters relative to lean mice. We hypothesise that this effect is mediated via FVT-induced GM changes.Significance of this studyWhat is already known about this subject?Obesity and type-2-diabetes (T2D) are associated with gut microbiota (GM) dysbiosis.Faecal microbiota transplant from lean donors has previously shown potential in treating obesity and T2D.Patients suffering from recurrent Clostridium difficile infections (rCDI) have been cured with sterile filtered donor faeces (containing enteric viruses and no bacteria), here defined as faecal virome transplantation (FVT).What are the new findings?FVT from lean donors lead to decreased weight gain and normalised blood sugar tolerance in a diet-induced obesity (DIO) mouse model.FVT significantly changed the bacterial and viral GM component, as well as the plasma metabolome and the expression profiles of obesity and T2D associated genes.Initial treatment with ampicillin prior FVT seems to counteract the beneficial effects associated with FVT.How might it impact on clinical practice in the foreseeable future?We here show a proof-of-concept, providing a solid base for designing a clinical study of FVT targeting obesity and T2D in humans. This is further augmented by the increased safety related to FVT, since bacteria and other microorganisms are removed from the donor faeces, and therefore minimises the risk of disease transmission.These findings highlight the potential application of FVT treatment of various diseases related to GM dysbiosis and further support the vital role of the viral community in maintaining and shaping the GM.


Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2131
Author(s):  
Shujuan Zheng ◽  
Yanan Wang ◽  
Jingjing Fang ◽  
Ruixuan Geng ◽  
Mengjie Li ◽  
...  

Previous studies have reported the therapeutic effects of oleuropein (OP) consumption on the early stage of type 2 diabetes. However, the efficacy of OP on the advanced stage of type 2 diabetes has not been investigated, and the relationship between OP and intestinal flora has not been studied. Therefore, in this study, to explore the relieving effects of OP intake on the advanced stage of type 2 diabetes and the regulatory effects of OP on intestinal microbes, diabetic db/db mice (17-week-old) were treated with OP at the dose of 200 mg/kg for 15 weeks. We found that OP has a significant effect in decreasing fasting blood glucose levels, improving glucose tolerance, lowering the homeostasis model assessment–insulin resistance index, restoring histopathological features of tissues, and promoting hepatic protein kinase B activation in db/db mice. Notably, OP modulates gut microbiota at phylum level, increases the relative abundance of Verrucomicrobia and Deferribacteres, and decreases the relative abundance of Bacteroidetes. OP treatment increases the relative abundance of Akkermansia, as well as decreases the relative abundance of Prevotella, Odoribacter, Ruminococcus, and Parabacteroides at genus level. In conclusion, OP may ameliorate the advanced stage of type 2 diabetes through modulating the composition and function of gut microbiota. Our findings provide a promising therapeutic approach for the treatment of advanced stage type 2 diabetes.


Author(s):  
Dominic Salamone ◽  
Angela Albarosa Rivellese ◽  
Claudia Vetrani

AbstractGut microbiota and its metabolites have been shown to influence multiple physiological mechanisms related to human health. Among microbial metabolites, short-chain fatty acids (SCFA) are modulators of different metabolic pathways. On the other hand, several studies suggested that diet might influence gut microbiota composition and activity thus modulating the risk of metabolic disease, i.e. obesity, insulin resistance and type 2 diabetes. Among dietary component, dietary fibre may play a pivotal role by virtue of its prebiotic effect on fibre-fermenting bacteria, that may increase SCFA production. The aim of this review was to summarize and discuss current knowledge on the impact of dietary fibre as modulator of the relationship between glucose metabolism and microbiota composition in humans. More specifically, we analysed evidence from observational studies and randomized nutritional intervention investigating the relationship between gut microbiota, short-chain fatty acids and glucose metabolism. The possible mechanisms behind this association were also discussed.


Gut Pathogens ◽  
2021 ◽  
Vol 13 (1) ◽  
Author(s):  
A. L. Cunningham ◽  
J. W. Stephens ◽  
D. A. Harris

AbstractA strong and expanding evidence base supports the influence of gut microbiota in human metabolism. Altered glucose homeostasis is associated with altered gut microbiota, and is clearly associated with the development of type 2 diabetes mellitus (T2DM) and associated complications. Understanding the causal association between gut microbiota and metabolic risk has the potential role of identifying susceptible individuals to allow early targeted intervention.


2021 ◽  
Author(s):  
Rocío Mateo-Gallego ◽  
Isabel Moreno-Indias ◽  
Ana M. Bea ◽  
Lidia Sánchez-Alcoholado ◽  
Antonio J. Fumanal ◽  
...  

An alcohol-free beer including the substitution of regular carbohydrates for low doses of isomaltulose and maltodextrin within meals significantly impacts gut microbiota in diabetic subjects with overweight or obesity.


2019 ◽  
Vol 10 (5) ◽  
pp. 2935-2946 ◽  
Author(s):  
Rongkang Hu ◽  
Feng Zeng ◽  
Linxiu Wu ◽  
Xuzhi Wan ◽  
Yongfang Chen ◽  
...  

Carrot juice fermented with Lactobacillus rhamnosus GG, enriched with free phenolics, organic acids and short-chain fatty acid, has the potential to ameliorate type 2 diabetes, in part through modulating specific gut microbiota and regulating the mRNA and protein expressions levels involved in glucose metabolism.


PLoS ONE ◽  
2015 ◽  
Vol 10 (1) ◽  
pp. e0116851 ◽  
Author(s):  
Yoshinori Watanabe ◽  
Keiko Nakayama ◽  
Nobuhiko Taniuchi ◽  
Yasushi Horai ◽  
Chiaki Kuriyama ◽  
...  

2011 ◽  
Vol 9 (3) ◽  
pp. 238-240 ◽  
Author(s):  
Inayat ur Rahman ◽  
Muhammad Idrees ◽  
Mohammad Salman ◽  
Rooh Ullah Khan ◽  
MI Khan ◽  
...  

Although management of hyperglycaemia represents one of the principal treatment goals of diabetes therapy, the high incidence of cardiovascular (CV) complications in diabetes also needs effective management. Therefore, the present study was designed to determine and compare the effect of glitazones on serum sialic acid (SSA), a known risk marker for CV disease, along with fasting plasma glucose (FPG), glycohaemoglobin (HbA1-c) and blood lipids, in overweight, previously only diet-treated patients with type 2 diabetes ( n=60). The study was conducted for a period of 12 months. Significant improvement in FPG and HbA1-c were shown by both rosiglitazone ( p<0.003 and p<0.001, respectively) and pioglitazone ( p<0.005 and p<0.001, respectively), compared with baseline, and pioglitazone showed greater beneficial effects on other parameters monitored, significantly reducing total cholesterol (TC) ( p≤0.05). Both the drugs showed a decrease in SSA and no significant differences were observed between the groups. However, the decrease was significant only in the pioglitazone-treated group at month 12 ( p≤0.05), compared with baseline. A significant decrease in SSA by pioglitazone indicates its greater cardioprotective effect compared with rosiglitazone.


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