Article

Effect of Kombucha on gut-microbiota in mouse having non-alcoholic fatty liver disease

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Abstract

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver disorders. Possible links have been recently found between the gut-microbiota and the host metabolism in development of NAFLD and obesity. Therefore, understanding the changes in intestinal microbiota during the progression of NAFLD, is important. In this study, the effect of Kombucha tea (KT), obtained by microbial fermentation of sugared black tea, was investigated on gut-microbiota during the progression of NAFLD. The results indicated a decrease in Erysipelotrichia class by treatment with KT in comparison to the methionine/choline-deficient (MCD)-fed db/db mice. Allobaculum, Turicibacter, and Clostridium genera, were only detected in MCD-fed db/db mice and were decreased after treatment with KT, whereas Lactobacillus was more abundant in MCD + KT-fed mice than in MCD only-fed mice and Mucispirillum, was found only in the MCD + KT-fed mice group. Our results demonstrated that the change of intestinal microbiota was influenced by KT intake, contributing to combat NAFLD. © 2018 The Korean Society of Food Science and Technology and Springer Science+Business Media B.V., part of Springer Nature

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The effect of Lactobacillus plantarum NCU116 on liver function, oxidative stress and lipid metabolism in rats with high fat diet induced non-alcoholic fatty liver disease (NAFLD) were studied. The rats were divided into four groups: normal diet (ND) group; high fat diet (HFD) group, HFD plus L. plantarum NCU116 two doses (NCU116-L, 108CFU/mL; NCU116-H, 109 CFU/mL) groups. Treatment of L. plantarum NCU116 for 5 weeks was found to restore liver function and oxidative stress in rats with NAFLD, and decrease the levels of fat accumulation in liver. In addition, the bacterium significantly reduced endotoxin and proinflammatory cytokines, and regulated bacterial flora in the colon and the expression of lipid metabolism in the liver. These results suggest that possible underlying mechanisms for beneficial effect of L. plantarum NCU116 on NAFLD may include two pathways of downregulating lipogenesis and upregulating lipolysis and fatty acid oxidation related genes expression.
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Unlabelled: Despite evidence that the intestinal microbiota (IM) is involved in the pathogenesis of obesity, the IM composition of patients with nonalcoholic fatty liver disease (NAFLD) has not been well characterized. This prospective, cross-sectional study was aimed at identifying differences in IM between adults with biopsy-proven NAFLD (simple steatosis [SS] or nonalcoholic steatohepatitis [NASH]) and living liver donors as healthy controls (HC). Fifty subjects were included: 11 SS, 22 NASH, and 17 HC. One stool sample was collected from each participant. Quantitative real-time polymerase chain reaction was used to measure total bacterial counts, Bacteroides/Prevotella (herein referred to as Bacteroidetes), Clostridium leptum, C. coccoides, bifidobacteria, Escherichia coli and Archaea in stool. Clinical and laboratory data, food records, and activity logs were collected. Patients with NASH had a lower percentage of Bacteroidetes (Bacteroidetes to total bacteria counts) compared to both SS and HC (P = 0.006) and higher fecal C. coccoides compared to those with SS (P = 0.04). There were no differences in the remaining microorganisms. As body mass index (BMI) and dietary fat intake differed between the groups (P < 0.05), we performed linear regression adjusting for these variables. The difference in C. coccoides was no longer significant after adjusting for BMI and fat intake. However, there continued to be a significant association between the presence of NASH and lower percentage Bacteroidetes even after adjusting for these variables (P = 0.002; 95% confidence interval = -0.06 to -0.02). Conclusion: There is an inverse and diet-/BMI-independent association between the presence of NASH and percentage Bacteroidetes in the stool, suggesting that the IM may play a role in the development of NAFLD.
Article
Unlabelled: Nonalcoholic steatohepatitis (NASH) is a serious liver disease associated with obesity. Characterized by metabolic syndrome, hepatic steatosis, and liver inflammation, NASH is believed to be under the influence of the gut microflora. Here, the composition of gut bacterial communities of NASH, obese, and healthy children was determined by 16S ribosomal RNA pyrosequencing. In addition, peripheral blood ethanol was analyzed to monitor endogenous ethanol production of patients and healthy controls. UniFrac-based principle coordinates analysis indicated that most of the microbiome samples clustered by disease status. Each group was associated with a unique pattern of enterotypes. Differences were abundant at phylum, family, and genus levels between healthy subjects and obese patients (with or without NASH), and relatively fewer differences were observed between obese and the NASH microbiomes. Among those taxa with greater than 1% representation in any of the disease groups, Proteobacteria, Enterobacteriaceae, and Escherichia were the only phylum, family and genus types exhibiting significant difference between obese and NASH microbiomes. Similar blood-ethanol concentrations were observed between healthy subjects and obese non-NASH patients, but NASH patients exhibited significantly elevated blood ethanol levels. Conclusions: The increased abundance of alcohol-producing bacteria in NASH microbiomes, elevated blood-ethanol concentration in NASH patients, and the well-established role of alcohol metabolism in oxidative stress and, consequently, liver inflammation suggest a role for alcohol-producing microbiota in the pathogenesis of NASH. We postulate that the distinct composition of the gut microbiome among NASH, obese, and healthy controls could offer a target for intervention or a marker for disease.
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To examine the impact of gut microbiota on non alcoholic fatty liver disease (NAFLD) pathogenesis. Emerging evidence suggests a strong interaction between gut microbiota and liver. Receiving approximately 70% of its blood supply from the intestine, the liver represents the first line of defence against gut-derived antigens. Intestinal bacteria play a key role in the maintenance of gut-liver axis health. Disturbances in the homeostasis between bacteria- and host-derived signals at the epithelial level lead to a break in intestinal barrier function and may foster "bacterial translocation", defined as the migration of bacteria or bacterial products from the intestinal lumen to mesenteric lymph nodes or other extraintestinal organs and sites. While the full repertoire of gut-derived microbial products that reach the liver in health and disease has yet to be explored, the levels of bacterial lipopolysaccharide, a component of the outer membrane of Gram-negative bacteria, are increased in the portal and/or systemic circulation in several types of chronic liver diseases. Derangement of the gut flora, particularly small intestinal bacterial overgrowth, occurs in a large percentage (20-75%) of patients with chronic liver disease. In addition, evidence implicating the gut-liver axis in the pathogenesis of metabolic liver disorders has accumulated over the past ten years. Complex metabolic diseases are the product of multiple perturbations under the influence of triggering factors such as gut microbiota and diet, thus, modulation of the gut microbiota may represent a new way to treat or prevent NAFLD.
Article
Maintenance of a reduced body weight is accompanied by a decrease in energy expenditure beyond that accounted for by reduced body mass and composition, as well as by an increased drive to eat. These effects appear to be due--in part--to reductions in circulating leptin concentrations due to loss of body fat. Gut microbiota have been implicated in the regulation of body weight. The effects of weight loss on qualitative aspects of gut microbiota have been studied in humans and mice, but these studies have been confounded by concurrent changes in diet composition, which influence microbial community composition. We studied the impact of 20% weight loss on the microbiota of diet-induced obese (DIO: 60% calories fat) mice on a high-fat diet (HFD). Weight-reduced DIO (DIO-WR) mice had the same body weight and composition as control (CON) ad-libitum (AL) fed mice being fed a control diet (10% calories fat), allowing a direct comparison of diet and weight-perturbation effects. Microbial community composition was assessed by pyrosequencing 16S rRNA genes derived from the ceca of sacrificed animals. There was a strong effect of diet composition on the diversity and composition of the microbiota. The relative abundance of specific members of the microbiota was correlated with circulating leptin concentrations and gene expression levels of inflammation markers in subcutaneous white adipose tissue in all mice. Together, these results suggest that both host adiposity and diet composition impact microbiota composition, possibly through leptin-mediated regulation of mucus production and/or inflammatory processes that alter the gut habitat.
Article
Nonalcoholic fatty liver disease affects up to 30% of the US population, but the mechanisms underlying this condition are incompletely understood. We investigated how diet standardization and choline deficiency influence the composition of the microbial community in the human gastrointestinal tract and the development of fatty liver under conditions of choline deficiency. We performed a 2-month inpatient study of 15 female subjects who were placed on well-controlled diets in which choline levels were manipulated. We used 454-FLX pyrosequencing of 16S ribosomal RNA bacterial genes to characterize microbiota in stool samples collected over the course of the study. The compositions of the gastrointestinal microbial communities changed with choline levels of diets; each individual's microbiome remained distinct for the duration of the experiment, even though all subjects were fed identical diets. Variations between subjects in levels of Gammaproteobacteria and Erysipelotrichi were directly associated with changes in liver fat in each subject during choline depletion. Levels of these bacteria, change in amount of liver fat, and a single nucleotide polymorphism that affects choline were combined into a model that accurately predicted the degree to which subjects developed fatty liver on a choline-deficient diet. Host factors and gastrointestinal bacteria each respond to dietary choline deficiency, although the gut microbiota remains distinct in each individual. We identified bacterial biomarkers of fatty liver that result from choline deficiency, adding to the accumulating evidence that gastrointestinal microbes have a role in metabolic disorders.
Article
Obesity was once rare, but the last few decades have seen a rapid expansion of the proportion of obese individuals worldwide. Recent work has shown obesity to be associated with a shift in the representation of the dominant phyla of bacteria in the gut, both in humans and animal models. This review summarizes the latest research into the association between microbial ecology and host adiposity, and the mechanisms by which microbes in the gut may mediate host metabolism in the context of obesity. Studies of the effect of excess body fat on the abundances of different bacteria taxa in the gut generally show alterations in the gastrointestinal microbiota, and changes during weight loss. The gastrointestinal microbiota have been shown to impact insulin resistance, inflammation, and adiposity via interactions with epithelial and endocrine cells. Large-scale alterations of the gut microbiota and its microbiome (gene content) are associated with obesity and are responsive to weight loss. Gut microbes can impact host metabolism via signaling pathways in the gut, with effects on inflammation, insulin resistance, and deposition of energy in fat stores. Restoration of the gut microbiota to a healthy state may ameliorate the conditions associated with obesity and help maintain a healthy weight.
Article
Obesity has recently been linked to the composition of human microbiota and the production of short chain fatty acids (SCFAs). However, these findings rely on experimental studies carried out using rather small and defined groups of volunteers or model animals. Our aim was to evaluate differences within the human intestinal microbiota and fecal SCFA concentration of lean and obese subjects. A total of 98 subjects volunteered to take part in this study. The BMI in kg/m(2) of 30 volunteers was within the lean range, 35 were overweight and 33 were obese. The fecal microbiota was characterized by real-time PCR analyses. With the primers used herein we were able to cover 82.3% (interquartile range of 68.3-91.4%) of the total microbiota detectable with a universal primer. In addition, the concentration of SCFA was evaluated. The total amount of SCFA was higher in the obese subject group (P = 0.024) than in the lean subject group. The proportion of individual SCFA changed in favor of propionate in overweight (P = 0.019) and obese subjects (P = 0.028). The most abundant bacterial groups in faeces of lean and obese subjects belonged to the phyla Firmicutes and Bacteroidetes. The ratio of Firmicutes to Bacteroidetes changed in favor of the Bacteroidetes in overweight (P = 0.001) and obese subjects (P = 0.005). Our results are in line with previous reports suggesting that SCFA metabolism might play a considerable role in obesity. However, our results contradict previous reports with regard to the contribution of various bacterial groups to the development of obesity and this issue remains controversial.
Article
Thirty-three patients were studied after intestinal bypass operations to determine if the postoperative hepatic steatosis could be related to bacterial overgrowth in the excluded segment, rather than to protein-calorie malnutrition. Metronidazole, a drug known to suppress anaerobic intestinal organisms, brought about improvement in the intestinal and systemic manifestations of the bypass enteropathy. When metronidazole was given at random intervals after surgery, the clinical improvement was associated with a reduction in hepatic steatosis in 12 of 12 patients. In 8 patients of this group, morphology reverted to normal within the first year. In contrast, without metronidazole treatment, steatosis increased in 12 of 17 patients during the postoperative period, only 1 reverted to normal in the first year, and in 9 of 12 patients the steatosis was still worse than at baseline during the second year after surgery. Additionally, in 9 patients, 3- or 4-mo periods with metronidazole were alternated repeatedly with drug-free intervals. Without metronidazole, steatosis increased in this group during 12 of 12 intervals, while in 12 of 13 periods with metronidazole, the steatosis diminished or disappeared. This improvement was evident despite concurrent progressive decreases in serum albumin levels during 5 of these 13 intervals. Overall, changes in hepatic fat content in the sequential liver biopsy specimens were found unrelated to weight loss rates or to plasma amino acid levels, and they inconsistently correlated to changes in serum albumin as indices of protein-calorie nutrition. The data of this study suggest that hepatic steatosis after an intestinal bypass operation is the result of a process related to the organisms colonizing the excluded intestinal segment, and that it is independent of protein-calorie malnutrition.
Article
We studied the influence of oligofructose (OFS), a nondigestible fructan, on lipid metabolism in obese fa/fa Zucker rats. The addition of 10 g/100 g OFS to the diet slowed the increase in body weight without modifying serum triglycerides or glucose concentrations after 7 wk of treatment. However, an oral load of 2 g glucose and 5 g corn oil/kg body weight increased triglyceridemia more in OFS-fed rats than in control rats. After 10 wk, OFS decreased the hepatic concentration of triglycerides 57% relative to controls. The less severe steatosis was confirmed by histologic analysis. Among the key enzymes involved in fatty acid synthesis and esterification, only malic enzyme activity was significantly lower in OFS-fed rats than in controls. The epididymal fat mass was significantly lower in OFS-fed rats. In conclusion, dietary enrichment with OFS can counteract both the fat mass development and the hepatic steatosis that occur in obese Zucker rats. Future studies will be designed to clarify in obese animals the influence of dietary OFS on postprandial triglyceridemia, which is an important variable associated with the development of atherosclerosis in humans, and to analyze the biochemical mechanism underlying the "hepatoprotective" effect of OFS.
Article
Kombucha was prepared in a tea broth (0.5% w/v) supplemented with sucrose (10% w/v) by using a commercially available starter culture. The pH decreased steadily from 5 to 2.5 during the fermentation while the weight of the "tea fungus" and the OD of the tea broth increased through 4 days of the fermentation and remained fairly constant thereafter. The counts of acetic acid-producing bacteria and yeasts in the broth increased up to 4 days of fermentation and decreased afterward. The antimicrobial activity of Kombucha was investigated against a number of pathogenic microorganisms. Staphylococcus aureus, Shigella sonnei, Escherichia coli, Aeromonas hydrophila, Yersinia enterolitica, Pseudomonas aeruginosa, Enterobacter cloacae, Staphylococcus epidermis, Campylobacter jejuni, Salmonella enteritidis, Salmonella typhimurium, Bacillus cereus, Helicobacterpylori, and Listeria monocytogenes were found to be sensitive to Kombucha. According to the literature on Kombucha, acetic acid is considered to be responsible for the inhibitory effect toward a number of microbes tested, and this is also valid in the present study. However, in this study, Kombucha proved to exert antimicrobial activities against E. coli, Sh. sonnei, Sal. typhimurium, Sal. enteritidis, and Cm. jejuni, even at neutral pH and after thermal denaturation. This finding suggests the presence of antimicrobial compounds other than acetic acid and large proteins in Kombucha.
Article
The human gut is the natural habitat for a large and dynamic bacterial community, but a substantial part of these bacterial populations are still to be described. However, the relevance and effect of resident bacteria on a host's physiology and pathology has been well documented. Major functions of the gut microflora include metabolic activities that result in salvage of energy and absorbable nutrients, important trophic effects on intestinal epithelia and on immune structure and function, and protection of the colonised host against invasion by alien microbes. Gut flora might also be an essential factor in certain pathological disorders, including multisystem organ failure, colon cancer, and inflammatory bowel diseases. Nevertheless, bacteria are also useful in promotion of human health. Probiotics and prebiotics are known to have a role in prevention or treatment of some diseases.
Article
Leptin is an adipocyte-secreted hormone with a key role in energy homeostasis. Studies in animal models, in humans with congenital complete leptin deficiency, and observational and interventional studies in humans with relative leptin deficiency (lower than normal leptin levels) have all indicated that leptin regulates multiple physiological functions, primarily in states of energy deficiency. This information led to proof-of-concept clinical trials involving leptin administration to individuals with relative or complete leptin deficiency. These conditions include congenital complete leptin deficiency, due to mutations in the leptin gene, and states of relative leptin deficiency including lipoatrophy and some forms of hypothalamic amenorrhea. Leptin, in replacement doses, normalizes neuroendocrine, metabolic and immune function in patients with these conditions, but further clinical studies are required to determine its long-term efficacy and safety. Management of leptin-deficient states with replacement doses of leptin holds promise as a therapeutic option. In addition, elucidation of the mechanisms underlying leptin resistance, which characterizes hyperleptinemic states such as human obesity and diabetes, might provide novel therapeutic targets for these prevalent clinical problems.
A core gut microbiome in obese and lean twins
  • P J Turnbaugh
  • M Hamady
  • T Yatsunenko
  • B L Cantarel
  • A Duncan
  • R E Ley
  • M L Sogin
  • W J Jones
  • B A Roe
  • J P Affourtit
  • PJ Turnbaugh