Helminth infection in mice improves insulin sensitivity via modulation of gut microbiota and fatty acid metabolism

Abstract

Intestinal helminths are prevalent in individuals who live in rural areas of developing countries, where obesity, type 2 diabetes, and metabolic syndrome are rare. In the present study, we analyzed the modulation of the gut microbiota in mice infected with the helminth Strongyloides venezuelensis, and fed either a standard rodent chow diet or high-fat diet (HFD). To investigate the effects of the microbiota modulation on the metabolism, we analyzed the expression of tight-junction proteins present in the gut epithelium, inflammatory markers in the serum and tissue and quantified glucose tolerance and insulin sensitivity and resistance. Additionally, the levels of lipids related to inflammation were evaluated in the feces and serum. Our results show that infection with Strongyloides venezuelensis results in a modification of the gut microbiota, most notably by increasing Lactobacillus spp. These modifications in the microbiota alter the host metabolism by increasing the levels of anti-inflammatory cytokines, switching macrophages from a M1 to M2 pattern in the adipose tissue, increasing the expression of tight junction proteins in the intestinal cells (thereby reducing the permeability) and decreasing LPS in the serum. Taken together, these changes correlate with improved insulin signaling and sensitivity, which could also be achieved with HFD mice treated with probiotics. Additionally, helminth infected mice produce higher levels of oleic acid, which participates in anti-inflammatory pathways. These results suggest that modulation of the microbiota by helminth infection or probiotic treatment causes a reduction in subclinical inflammation, which has a positive effect on the glucose metabolism of the host.

Faecalibacterium prausnitzii‐derived microbial anti‐inflammatory molecule regulates intestinal integrity in diabetes mellitus mice via modulating tight junction protein expression

“…Recent findings suggest that moderate gut dysbiosis exists in DM patients and animal models . Although the characteristics of the DM gut microbiome are still mired in controversy, gut microbiome studies have hinted at the biological functions or pathogenic roles of gut microbiota in DM progression . The differential richness of specific bacteria is potentially correlated with DM development .…”

“…[10][11][12][13] Although the characteristics of the DM gut microbiome are still mired in controversy, gut microbiome studies have hinted at the biological functions or pathogenic roles of gut microbiota in DM progression. [14][15][16] The differential richness of specific bacteria is potentially correlated with DM development. 17 Faecalibacterium prausnitzii (F. prausnitzii) are the predominant butyrateproducing bacteria in the gastrointestinal tract.…”

Scutellariae Radix and Coptidis Rhizoma Improve Glucose and Lipid Metabolism in T2DM Rats via Regulation of the Metabolic Profiling and MAPK/PI3K/Akt Signaling Pathway

“…Among the varieties of analytical platforms used for metabonomic analysis, the use of ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) is steadily increasing due to its better reproducibility and detection limits, and increased chromatographic resolution, which can assess all metabolites in biological samples and provide insights into the holistic efficacy of TCMs. Besides, the extent of metabolic changes and types of metabolites could be applied as good markers during insulin resistance [ 20 ].…”

The interplay of type 2 immunity, helminth infection and the microbiota in regulating metabolism

“…H. polygyrus, N. brasiliensis and T. muris infections were all shown to induce an increase in Lactobacillaceae, and members of this family are widely recognised as having probiotic potential by virtue of their ability to regulate immune responsiveness . Recently, a study investigating Strongyloides venezuelensis and DIO showed an improvement of insulin sensitivity upon infection, and these benefits were linked to a modification of microbiota, including an increase in several species of Lactobacillus, and a reduction of intestinal permeability (Figure ) . As mentioned earlier, one recent study reported that the beneficial effects of H. polygyru s infection on DIO in mice were positively associated with a modification of the microbiota leading to an increased level of circulating NE .…”

“…76,87,88 Recently, a study investigating Strongyloides venezuelensis and DIO showed an improvement of insulin sensitivity upon infection, and these benefits were linked to a modification of microbiota, including an increase in several species of Lactobacillus, and a reduction of intestinal permeability (Figure 2). 89 As mentioned earlier, one recent study reported that the beneficial effects of H. polygyrus infection on DIO in mice were positively associated with a modification of the microbiota leading to an increased level of circulating NE. 70 As also mentioned earlier, adapting to stress, such a helminth infection, requires proper energetic balance and helminths are able to alter glucose uptake within the intestine, 62 likely resulting in restricted caloric intake.…”