Project description:We explore whether a low-energy diet intervention for Metabolic dysfunction-associated steatohepatitis (MASH) improves liver disease by means of modulating the gut microbiome. 16 individuals were given a low-energy diet (880 kcal, consisting of bars, soups, and shakes) for 12 weeks, followed by a stepped re-introduction to whole for an additional 12 weeks. Stool samples were obtained at 0, 12, and 24 weeks for microbiome analysis. Fecal microbiome were measured using 16S rRNA gene sequencing. Positive control (Zymo DNA standard D6305) and negative control (PBS extraction) were included in the sequencing. We found that low-energy diet improved MASH disease without lasting alterations to the gut microbiome.
Project description:Obesity and overweight are closely related to diet, and gut microbiota play an important role in body weight and human health. The aim of this study was to explore how Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 supplementation alleviate obesity by modulating the human gut microbiome. A randomized, double-blind, placebo-controlled study was conducted on 72 overweight individuals. Over a 12-week period, probiotic groups consumed 5×10^9 colony-forming units of HY7601 and KY1032), whereas the placebo group consumed the same product without probiotics. After treatment, the probiotic group displayed a reduction in body weight (p <0.001), visceral fat mass (p <0.025), and waist circumference (p <0.007), and an increase in adiponectin (p <0.046), compared with the placebo group. Additionally, HY7601 and KY1032 supplementation modulated bacterial gut microbiota characteristics and beta diversity by increasing Bifidobacteriaceae and Akkermansiaceae, and decreasing Prevotellaceae and Selenomonadaceae. In summary, HY7601 and KY1032 probiotics exert anti-obesity effects by regulating the gut microbiota; hence, they have therapeutic potential for preventing or alleviating obesity and overweight.
Project description:Diet can regulate gene and microRNA (miRNA) expression and various biological processes in the gut. Dietary interventions have been proposed as therapeutic approaches for several diseases, including cancer. In a pilot study, we showed that a low-inflammatory Mediterranean diet reduced markers of local and systemic inflammation in 27 patients with Familial Adenomatous Polyposis (FAP). We evaluated the changes induced by a low-inflammatory Mediterranean dietary intervention on fecal miRNome and intestinal tissue transcriptome in FAP subjects and assessed whether these changes could be associated with the beneficial effects observed in the pilot study. The diet modulated 41 fecal miRNAs, and this modulation remained for three months after the intervention. miR-5092-5p, miR-4527, and miR-3612-3p were positively correlated with adherence to the Mediterranean diet, while miR-6867-5p and miR-760-5p were negatively correlated with serum calprotectin levels. The altered miRNAs target genes mainly related to inflammatory pathways, DNA repair, metabolism, and cytoskeleton organization. Seventy genes were differentially expressed between adenoma and normal tissue. Most were different before the dietary intervention, but reached similar levels after the diet. Functional enrichment analysis identified the proinflammatory ERK1/2, cell cycle regulation and nutrient response pathways as commonly regulated by differentially expressed miRNAs and genes. These findings suggest that fecal miRNAs modulated by the diet reflect an epigenetic regulation occurring in tissues that seems to influence inflammatory pathways. miRNAs and genes with oncogenic and tumor suppressor functions are also regulated, highlighting the potential cancer-preventive effect of the low-inflammatory Mediterranean diet.
Project description:Complex oligosaccharides found in human milk play a vital role in gut microbiome development for the human infant. Bovine milk oligosaccharides (BMO) have similar structures with those derived from human milk, but have not been well studied for their effects on the healthy adult human gut microbiome. Healthy human subjects consumed BMO over two-week periods at two different doses and provided fecal samples. Metatranscriptomics of fecal samples was conducted to determine microbial and host gene expression in response to the supplement. Fecal samples were also analyzed by mass spectrometry to determine levels of undigested BMO. No changes were observed in microbiome activity across all participants. Repeated sampling enabled subject-specific analyses: four of six participants had minor, yet statistically significant, changes in microbial activity. No significant change was observed in the gene expression of host cells in stool. Levels of BMO excreted in feces after supplementation were not significantly different from placebo and were not correlated with dosage or expressed microbial enzyme levels. Collectively, these data suggest that BMO is fully digested in the human gastrointestinal tract prior to stool collection. Participants’ gut microbiomes remained stable but varied between individuals. Additionally, the unaltered host transcriptome provides further evidence for the safety of BMO as a dietary supplement or food ingredient.
Project description:Pancreatic cancer is the 3rd most prevalent cause of cancer related deaths in United states alone, with over 55000 patients being diagnosed in 2019 alone and nearly as many succumbing to it. Late detection, lack of effective therapy and poor understanding of pancreatic cancer systemically contributes to its poor survival statistics. Obesity and high caloric intake linked co-morbidities like type 2 diabetes (T2D) have been attributed as being risk factors for a number of cancers including pancreatic cancer. Studies on gut microbiome has shown that lifestyle factors as well as diet has a huge effect on the microbial flora of the gut. Further, modulation of gut microbiome has been seen to contribute to effects of intensive insulin therapy in mice on high fat diet. In another study, abnormal gut microbiota was reported to contribute to development of diabetes in Db/Db mice. Recent studies indicate that microbiome and microbial dysbiosis plays a role in not only the onset of disease but also in its outcome. In colorectal cancer, Fusobacterium has been reported to promote therapy resistance. Certain intra-tumoral bacteria have also been shown to elicit chemo-resistance by metabolizing anti-cancerous agents. In pancreatic cancer, studies on altered gut microbiome have been relatively recent. Microbial dysbiosis has been observed to be associated with pancreatic tumor progression. Modulation of microbiome has been shown to affect response to anti-PD1 therapy in this disease as well. However, most of the studies in pancreatic cancer and microbiome have remained focused om immune modulation. In the current study, we observed that in a T2D mouse model, the microbiome changed significantly as the hyperglycemia developed in these animals. Our results further showed that, tumors implanted in the T2D mice responded poorly to Gemcitabine/Paclitaxel (Gem/Pac) standard of care compared to those in the control group. A metabolomic reconstruction of the WGS of the gut microbiota further revealed that an enrichment of bacterial population involved in drug metabolism in the T2D group.
Project description:Southern European countries have some of the highest life expectancies in the world, yet they display high frailty. Here, we examined different diets to identify compositions that promote both healthspan and strength. In genetically diverse mice, the western and ketogenic diets increased fat mass, insulin resistance, and cholesterol levels. In contrast, a low-protein pescatarian Longevity Diet (LD), combining traditional Mediterranean and Okinawan features with moderate methionine supplementation (LDMM) or a fasting-mimicking diet (FMD), reduced fat mass and frailty while improving cardiometabolic markers. The normocaloric LDMM reduced IGF-1 while increasing growth hormone, GLP-1, and FGF21, which was crucial for diet-induced fat loss and improved insulin sensitivity. These findings indicate that high methionine intake may partially explain the major increase in overweight and diabetes in epidemiological studies of subjects who maintain a healthy lifestyle but consume a high animal protein diet, but not in those consuming a high plant protein diet.
Project description:Diet can regulate gene and microRNA (miRNA) expression and various biological processes in the gut. Dietary interventions have been proposed as therapeutic approaches for several diseases, including cancer. In a pilot study, we showed that a low-inflammatory Mediterranean diet reduced markers of local and systemic inflammation in patients with Familial Adenomatous Polyposis (FAP). We evaluated the changes induced by a low-inflammatory Mediterranean dietary intervention on fecal miRNome and intestinal tissue transcriptome in FAP subjects and assessed whether these changes could be associated with the beneficial effects observed in the pilot study. The diet modulated 41 fecal miRNAs, and this modulation remained for three months after the intervention. miR-5092-5p, miR-4527, and miR-3612-3p were positively correlated with adherence to the Mediterranean diet, while miR-6867-5p and miR-760-5p were negatively correlated with serum calprotectin levels. The altered miRNAs target genes mainly related to inflammatory pathways, DNA repair, metabolism, and cytoskeleton organization. Seventy genes were differentially expressed between adenoma and normal tissue. Most were different before the dietary intervention, but reached similar levels after the diet. Functional enrichment analysis identified the proinflammatory ERK1/2, cell cycle regulation and nutrient response pathways as commonly regulated by differentially expressed miRNAs and genes. These findings suggest that fecal miRNAs modulated by the diet reflect an epigenetic regulation occurring in tissues that seems to influence inflammatory pathways. miRNAs and genes with oncogenic and tumor suppressor functions are also regulated, highlighting the potential cancer-preventive effect of the low-inflammatory Mediterranean diet.
Project description:Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut, but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals, reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids and the outgrowth of microorganisms capable of triggering inflammatory bowel disease. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles. RNA-Seq analysis of the human gut microbiome during consumption of a plant- or animal-based diet.
Project description:This study aimed to identify the effects of replacement of saturated fat (SFA) by monunsaturated fat (MUFA) in a western-type diet and the effects of a full Mediterranean (MED) diet on whole genome PBMC gene expression and plasma protein profiles. Abdominally overweight subjects were randomized to a 8 wk completely controlled SFA-rich diet, a SFA-by-MUFA-replaced diet (MUFA diet) or a MED diet. Concentrations of 124 plasma proteins and PBMCs whole genome transcriptional profiles were assessed. Consumption of the MUFA and MED diet, compared with the SFA diet, decreased expression of oxidative phosphorylation (OXPHOS) genes, serum lipids and plasma Connective Tissue Growth Factor, myoglobin and Apo B concentrations. The MED diet additional lowered plasma α-2-macroglobulin concentration compared with the SFA diet. Within the MED diet group concentrations of several pro-inflammatory proteins were lowered. We conclude that MUFA as replacement of SFA in a western-type diet or in a MED diet had similar effects on lowering expression of OXPHOS genes. We hypothesize that replacement of SFA by MUFA increased metabolic health as reflected by lowered serum lipids and certain plasma proteins, thereby reducing metabolic stress and OXPHOS activity in PBMCs. The MED diet may have additional anti-atherogenic effects by lowering concentrations of pro-inflammatory plasma proteins. Expression profiling by array
Project description:Mediterranean diet intervention in overweight and obese subjects leads to multiple beneficial shifts in gut microbiome and metabolome independently from energy intake