Various disease states are associated with an imbalance of protective and pathogenic bacteria in the gut, termed dysbiosis. Current evidence reveals that dietary factors affect the microbial ecosystem in the gut. Changes to community structure of the intestinal microbiota are not without consequence considering the wide effects that the microbes have on both local and systemic immunity. The goal of this review is to give insight into the importance of gut microbiota in disease development and the possible therapeutic interventions in clinical settings. We introduce the complex tripartite relationship between diet, microbes and the gut epithelium. This is followed by a summary of clinical evidence of diet-induced dysbiosis as a contributing factor in the development of gastrointestinal diseases like inflammatory bowel disease, irritable bowel syndrome and colorectal cancer, as well as systemic diseases like obesity, diabetes, atherosclerosis and nonalcoholic fatty liver disease. Finally, the current dietary and microbial interventions to promote a healthy microbial profile will be reviewed.

BackgroundAtherosclerosis appears to have multifactorial causes – microbial component like lipopolysaccharides (LPS) and other pathogen associated molecular patterns may be plausible factors. The gut microbiota is an ample source of such stimulants, and its dependent metabolites and altered gut metagenome has been an established link to atherosclerosis. In this exploratory pilot study, we aimed to elucidate whether microbial intervention with probiotics L. rhamnosus GG (LGG) or pharmaceuticals telmisartan (TLM) could improve atherosclerosis in a gut microbiota associated manner.MethodsAtherosclerotic phenotype was established by 12 weeks feeding of high fat (HF) diet as opposed to normal chow diet (ND) in apolipoprotein E knockout (ApoE−/−) mice. LGG or TLM supplementation to HF diet was studied.ResultsBoth LGG and TLM significantly reduced atherosclerotic plaque size and improved various biomarkers including endotoxin to different extents. Colonial microbiota analysis revealed that TLM restored HF diet induced increase in Firmicutes/Bacteroidetes ratio and decrease in alpha diversity; and led to a more distinct microbial clustering closer to ND in PCoA plot. Eubacteria, Anaeroplasma, Roseburia, Oscillospira and Dehalobacteria appeared to be protective against atherosclerosis and showed significant negative correlation with atherosclerotic plaque size and plasma adipocyte – fatty acid binding protein (A-FABP) and cholesterol.ConclusionLGG and TLM improved atherosclerosis with TLM having a more distinct alteration in the colonic gut microbiota. Altered bacteria genera and reduced alpha diversity had significant correlations to atherosclerotic plaque size, plasma A-FABP and cholesterol. Future studies on such bacterial functional influence in lipid metabolism will be warranted.

The association between obesity and heart failure is well documented and recent studies have indicated that understanding the physiological role of autophagy will be of great significance. Cardiomyocyte apoptosis is one component of cardiac remodeling which leads to heart failure and in this study we used palmitate-treated H9c2 cells as an in vitro model of lipotoxicity to investigate the role of autophagy in cell death. Temporal analysis revealed that palmitate (100 μM) treatment induced a gradual increase of intracellular lipid accumulation as well as apoptotic cell death. Palmitate induced autophagic flux, determined via increased LC3-II formation and p62 degradation as well as by detecting reduced colocalization of GFP with RFP in cells overexpressing tandem fluorescent GFP/RFP-LC3. The increased level of autophagy indicated by these measures were confirmed using transmission electron microscopy (TEM). Upon inhibiting autophagy using bafilomycin we observed an increased level of palmitate-induced cell death assessed by Annexin V/PI staining, detection of active caspase-3 and MTT cell viability assay. Interestingly, using TEM and p-PERK or p-eIF2α detection we observed increased endoplasmic reticulum (ER) stress in response to palmitate. Autophagy was induced as an adaptive response against ER stress since it was sensitive to ER stress inhibition. Palmitate-induced ER stress also induced adiponectin resistance, assessed via AMPK phosphorylation, via reducing APPL1 expression. This effect was independent of palmitate-induced autophagy. In summary, our data indicate that palmitate induces autophagy subsequent to ER stress and that this confers a prosurvival effect against lipotoxicity-induced cell death. Palmitate-induced ER stress also led to adiponecin resistance.

The dynamics of the tripartite relationship between the host, gut bacteria and diet in the gut is relatively unknown. An imbalance between harmful and protective gut bacteria, termed dysbiosis, has been linked to many diseases and has most often been attributed to high-fat dietary intake. However, we recently clarified that the type of fat, not calories, were important in the development of murine colitis. To further understand the host-microbe dynamic in response to dietary lipids, we fed mice isocaloric high-fat diets containing either milk fat, corn oil or olive oil and performed 16S rRNA gene sequencing of the colon microbiome and mass spectrometry-based relative quantification of the colonic metaproteome. The corn oil diet, rich in omega-6 polyunsaturated fatty acids, increased the potential for pathobiont survival and invasion in an inflamed, oxidized and damaged gut while saturated fatty acids promoted compensatory inflammatory responses involved in tissue healing. We conclude that various lipids uniquely alter the host-microbe interaction in the gut. While high-fat consumption has a distinct impact on the gut microbiota, the type of fatty acids alters the relative microbial abundances and predicted functions. These results support that the type of fat are key to understanding the biological effects of high-fat diets on gut health.