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1.	Caesar, R, et al. (författare) Effects of gut microbiota on obesity and atherosclerosis via modulation of inflammation and lipid metabolism. 2010 Ingår i: Journal of internal medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 268:4, s. 320-8 Tidskriftsartikel (refereegranskat)abstract Recent studies have revealed a close relationship between inflammatory and metabolic pathways, and inflammation is now recognized to have a major role in obesity and metabolic diseases such as insulin resistance and atherosclerosis. The human body is home to a large number of distinct microbial communities, with the densest population in the distal gut (the gut microbiota). Bacteria have long been known to activate inflammatory pathways, and recent data demonstrate that the gut microbiota may affect lipid metabolism and function as an environmental factor that influences the development of obesity and related diseases. Here, we review how the gut microbiota may affect metabolic diseases by activating the innate immune system.
2.	Fåk, Frida, et al. (författare) Age-related Effects of the Probiotic Bacterium Lactobacillus plantarum 299v on Gastrointestinal Function in Suckling Rats 2008 Ingår i: Digestive Diseases and Sciences. - : Springer Science and Business Media LLC. - 1573-2568 .- 0163-2116. ; 53:664-671, s. 664-671 Tidskriftsartikel (refereegranskat)abstract The effect of a probiotic bacterium on gut function was studied in neonatal animals by using a model with suckling rats. Lactobacillus plantarum 299v (Lp299v) or saline (controls) was fed (3.0 x 10(6) CFU/g b.wt per day) for one week to rats aged either 3, 7 or 14 days, after which bacterial colonization, gut growth, and functional parameters were analyzed. In rats fed with Lp299v from 3 to 10 days of age, an increase in ceacal lactobacilli was correlated with reduced intestinal macromolecular permeability and increased mucosal protein compared to age-matched controls. Pups treated from 7 to 14 days of age showed a decrease in pancreas weight and protein content, whereas pups treated from 14 to 21 days of age showed little effect of the Lp299v treatment. The results indicated that the bacterial exposure affected the gut function, where the effects were age-related and the youngest rats appeared most sensitive.
3.	Fåk, Frida, et al. (författare) Effects of a high-fat diet during pregnancy and lactation are modulated by E. coli in rat offspring 2012 Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 36:5, s. 744-751 Tidskriftsartikel (refereegranskat)abstract Objective: Microbial manipulations in early life can affect gut development and inflammatory status of the neonate. The maternal diet during pregnancy and lactation also influences the health of the offspring, but the impact of maternal high-fat (HF) feeding along with modulations of the gut microbiota on body weight, fat deposition and gut function in the offspring has been poorly studied. Methods: Rat dams were given access to either an HF or a standard low-fat diet during the last 2 weeks of pregnancy and during lactation and effects on body weight and gastrointestinal function were investigated in the 14-day-old offspring. To elucidate whether bacterial administration to the dam could modulate any effects of the diets in the rat pups, another group of dams were given Escherichia coli in their drinking water. Results: Maternal HF feeding resulted in increased body and fat pad weights in the offspring, along with increased levels of the acute-phase protein, haptoglobin and decreased protein content and disaccharidase activities in the small intestine. The addition of E. coli further accentuated these responses in the young rats, which, in addition to higher body weights and increased fat deposition, also showed an increased intestinal permeability and elevated levels of haptoglobin. Conclusions: The present study demonstrates for the first time how bacterial administration to the maternal diet during the neonatal period can affect body weight and fat deposition in the offspring. The results point to a mechanistic link between the gut microbiota, increased intestinal permeability and metabolic endotoxemia, which appear to have led to increased adiposity in the young rats. International Journal of Obesity (2012) 36, 744-751; doi:10.1038/ijo.2011.118; published online 5 July 2011
4.	Fåk, Frida, et al. (författare) Gastric ghrelin cell development is hampered and plasma ghrelin is reduced by delayed weaning in rats 2007 Ingår i: Journal of Endocrinology. - : Bioscientifica. - 1479-6805 .- 0022-0795. ; 192:2, s. 345-352 Tidskriftsartikel (refereegranskat)abstract The duration of breastfeeding has attracted much interest, as a prolonged period of breastfeeding has been shown to reduce the risk of developing obesity. The mechanism behind the reduced risk is, however, poorly understood. The novel hormone ghrelin augments appetite, promotes body. weight increase and increases adiposity. The majority of circulating ghrelin emanates from endocrine cells in the oxyntic mucosa of the stomach. In newborn humans and rodents, the number of ghrelin cells is low after birth until weaning, when the cell population is greatly expanded. To date, information about the influence of weaning perturbations on ghrelin cell development is scarce. Therefore, we studied the effect of delayed weaning on gastric ghrelin expression and plasma ghrelin concentration. To this end, special food separator cages were used to prevent the pups from eating solid food, forcing them to drink milk up to 21 days of age. Gastric ghrelin expression was examined by immunocytochemistry and in situ hybridisation, and plasma concentrations were assessed by RIA. Our data showed that gastric ghrelin expression and plasma ghrelin concentration are maintained at a lower level by delayed weaning. We also found that the relation between gastric ghrelin expression and body weight was altered by delayed weaning. Thus, control rats displayed a positive correlation between ghrelin expression and body weight, while no such correlation was evident in animals with delayed weaning. We conclude that delayed weaning exerts a negative influence on ghrelin expression, and that the onset of solid food intake may trigger normal ghrelin expression. Therefore, we suggest that ghrelin may constitute a hormonal link between the duration of breastfeeding and body weight development.
5.	Fåk, Frida (författare) Impact of the gut microflora on the digestive system in the suckling rat 2007 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract The postnatal development of the gastrointestinal (GI) system in mammals is genetically programmed, but is, to an unknown extent, regulated by external factors such as the diet and the gut microflora. These factors can influence the growth of the GI tract, the age-related pattern of appearance of digestive enzymes and the decreased intestinal macromolecular permeability at gut closure, normally timed with weaning in young rodents. The main focus of this doctoral thesis was to elucidate the effect of the colonizing gut microflora as well as to clarify the impact of the maternal microflora on the GI development in rat pups using pro-, pre- and antibiotic manipulations. The suckling rat model was chosen, because the rat is born immature enabling manipulations during its GI development. A probiotic bacterium, Lactobacillus plantarum 299v (Lp299v), having significant health effects in humans and animals and E. coli (CCUG 29300T), an opportunistic bacterium of the family Enterobacteriaceae, as well as broad spectrum antibiotics or a prebiotic inulin preparation, Synergy1, were administered, either directly by gavage to rat pups at various ages during the suckling period, or via the rat dam by administering bacteria or antibiotics in the drinking water. Taken together the results showed that manipulating the gut microflora, either directly or via the mother, affected the growth and function of the GI tract and its associated organs in suckling rats. The effect of Lp299v was age-dependent, where pups colonized early after birth or being offspring born from dams consuming the bacterium showed the greatest impact on the gut function. An altered maternal bacterial flora, induced by antibiotic treatment and E. coli exposure of dams, transfers to the offspring with increased cecal densities of Enterobacteriaceae in the rat pups, which affected the GI development. Moreover, the pups of dams treated with antibiotics showed a delayed stomach development, while the pups of E. coli dams showed an increased growth of the GI system. Increased blood levels of haptoglobin, indicating inflammation, were observed in both groups of pups, which was not seen in the Lp299v exposed pups. Thus, the effects on the GI system are not likely merely mediated by inflammation. Stimulation of the endogenous microflora, by feeding a fiber preparation, enhanced intestinal growth and function in suckling rats. Abstract _________________________________________________________________________ The results obtained in this thesis broaden the knowledge of the impact of specific bacterial groups for growth and function of the digestive system and can hopefully be applied for the care of neonates. The fact that increased numbers of Enterobacteriaceae during the suckling period leads to inflammation might improve our understanding of the “hygiene hypothesis” and the pathogenesis of inflammatory and immune-related bowel diseases in neonates.
6.	Fåk, Frida, et al. (författare) Lactobacillus reuteri Prevents Diet-Induced Obesity, but not Atherosclerosis, in a Strain Dependent Fashion in Apoe-/- Mice 2012 Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 7:10 Tidskriftsartikel (refereegranskat)abstract Objective: To investigate whether the specific strains of Lactobacillus reuteri modulates the metabolic syndrome in Apoe-/- mice. Methods: 8 week-old Apoe-/- mice were subdivided into four groups who received either L. reuteri ATCC PTA 4659 (ATCC), DSM 17938 (DSM), L6798, or no bacterial supplement in the drinking water for 12 weeks. The mice were fed a high-fat Western diet with 0.2% cholesterol and body weights were monitored weekly. At the end of the study, oral glucose and insulin tolerance tests were conducted. In addition, adipose and liver weights were recorded along with analyses of mRNA expression of ileal Angiopoietin-like protein 4 (Angptl4), the macrophage marker F4/80 encoded by the gene Emr1 and liver Acetyl-CoA carboxylase 1 (Acc1), Fatty acid synthase (Fas) and Carnitine palmitoyltransferase 1a (Cpt1a). Atherosclerosis was assessed in the aortic root region of the heart. Results and Conclusions: Mice receiving L. reuteri ATCC gained significantly less body weight than the control mice, whereas the L6798 mice gained significantly more. Adipose and liver weights were also reduced in the ATCC group. Serum insulin levels were lower in the ATCC group, but no significant effects were observed in the glucose or insulin tolerance tests. Lipogenic genes in the liver were not altered by any of the bacterial treatments, however, increased expression of Cpt1a was found in the ATCC group, indicating increased beta-oxidation. Correspondingly, the liver trended towards having lower fat content. There were no effects on inflammatory markers, blood cholesterol or atherosclerosis. In conclusion, the probiotic L. reuteri strain ATCC PTA 4659 partly prevented diet-induced obesity, possibly via a previously unknown mechanism of inducing liver expression of Cpt1a.
7.	Fåk, Frida, et al. (författare) Maternal consumption of Lactobacillus plantarum 299v affects gastrointestinal growth and function in the suckling rat. 2008 Ingår i: British Journal of Nutrition. - 1475-2662. ; 100:2, s. 332-338 Tidskriftsartikel (refereegranskat)abstract After birth, the gastrointestinal (GI) tract undergoes vast structural and functional adaptations to be able to digest mother's milk and later, during the weaning period, solid food. Studies on germ-free animals have shown the role of the gut microbiota for stimulating GI maturation, but which groups are involved is unclear. In the present study, we administered the probiotic bacterium, Lactobacillus plantarum 299v (Lp299v), in the drinking water to pregnant and lactating rat dams until their pups had reached an age of 14 d. It was found that Lp299v colonizing the mothers were also able to colonize the pups, which had an impact on their gut growth and function. The small intestine, pancreas and liver weighed more in the 14 d-old pups born from dams exposed to Lp299v than in the control pups from dams given only water. Furthermore, the Lp299v pups showed decreased gut permeability. Despite a heavier spleen in the Lp299v pups, as compared to the control pups, no significant increase in the acute-phase protein, haptoglobin, was found. In conclusion, the results reported here clearly show that manipulating the maternal microflora by exposing expecting mothers to a Gram-positive, probiotic bacterium prior to parturition and during lactation impacts the gut growth and function in the offspring.
8.	Fåk, Frida, et al. (författare) Microbial manipulation of the rat dam changes bacterial colonization and alters properties of the gut in her offspring. 2008 Ingår i: American Journal of Physiology: Gastrointestinal and Liver Physiology. - : American Physiological Society. - 1522-1547 .- 0193-1857. ; 294, s. 148-154 Tidskriftsartikel (refereegranskat)abstract The impact of an altered bacterial colonization on gut development has not been thoroughly studied, despite the increased risk of certain diseases with a disturbed microbiota after birth. This study was conducted to determine the effect of microbial manipulation, i.e. antibiotic treatment or Escherichia coli (E. coli) exposure, of the dam on bacterial colonization and gut development in the offspring. Pregnant rats were administered either broad-spectrum antibiotics three days prior to parturition, or live non-pathogenic E. coli CCUG 29300T one week before parturition and up to 14 days of lactation in the drinking water. Caecal bacterial levels, gut growth, intestinal permeability, digestive enzyme levels and intestinal inflammation were studied in two-week old rats. Pups from dams that were antibiotic-treated had higher densities of Enterobacteriaceae which correlated with a decreased stomach growth and function, lower pancreatic protein levels, higher intestinal permeability and increased plasma levels of the acute phase protein, haptoglobin, compared with pups from untreated mothers. Exposure of pregnant/lactating mothers to E. coli CCUG 29300T, also resulting in increased Enterobacteriaceae levels, gave in the offspring similar results on the stomach and an increased small intestinal growth as compared to the control pups. Furthermore, E. coli pups showed increased mucosal disaccharidase activities, increased liver, spleen and adrenal weights, as well as increased plasma concentrations of haptoglobin. These findings indicate that disturbing the normal bacterial colonization after birth, by increasing the densities of caecal Enterobacteriaceae, appear to have lasting effects on the postnatal microflora which affects gut growth and function.
9.	Fåk, Frida, et al. (författare) Microbial manipulation of the rat dam results in changed colonization and altered properties of the gut in her offspring 2007 Ingår i: American Journal of Physiology: Gastrointestinal and Liver Physiology. - 1522-1547. ; 294, s. 148-154 Tidskriftsartikel (refereegranskat)
10.	Fåk, Frida, et al. (författare) Oral microbiota in patients with atherosclerosis 2015 Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150. ; 243:2, s. 573-578 Tidskriftsartikel (refereegranskat)abstract Background and aims: Recent evidence suggests that the microbiota may be considered as an environmental factor that contributes to the development of atherosclerosis. Periodontal disease has been associated with cardio- and cerebrovascular events, and inflammation in the periodontium is suggested to increase the systemic inflammatory level of the host, which may in turn influence plaque composition and rupture. We previously showed that bacteria from the oral cavity and the gut could be found in atherosclerotic plaques. Methods: To elucidate whether the oral microbiota composition differed between patients with asymptomatic and symptomatic atherosclerosis we performed pyrosequencing of the oral microbiota of 92 individuals including patients with asymptomatic and symptomatic atherosclerosis and control individuals without carotid plaques or previous stroke or myocardial infarction. Results: The overall microbial structure was similar in controls and atherosclerosis patients, but patients with symptomatic atherosclerosis had higher relative abundance of Anaeroglobus (mean 0.040% (SD 0.049)) than the control group (0.010% (SD 0.028)) (P = 0.03). Using linear regression analysis, we found that Parvimonas associated positively with uCRP and Capnocytophaga, Catonella and Lactobacillus associated with blood lipid markers. In conclusion, abundance of Anaeroglobus in the oral cavity could be associated with symptomatic atherosclerosis. © 2015 Elsevier Ireland Ltd.
11.	Fåk, Frida (författare) The gut microbiota : A predisposing factor in obesity, diabetes and atherosclerosis 2016 Ingår i: The Human Microbiota and Chronic Disease: Dysbiosis as a Cause of Human Pathology. - Hoboken, NJ, USA : John Wiley & Sons, Inc.. - 9781118982877 - 9781118982907 ; , s. 351-359 Bokkapitel (refereegranskat)abstract The cluster of pathologies comprising the metabolic syndrome (MetS) includes increased waist circumference, hyperglycemia, elevated blood pressure and hyperlipidemia. With time, these conditions present a major risk of developing obesity, type 2 diabetes and atherosclerosis. Fecal microbiota transplant (FMT) experiments performed in mice have given an intriguing foundation for a microbial-based therapy of obesity in humans. In the years 2004 - 2009, Gordon and colleagues presented ground-breaking studies on the role of the gut microbiota in host energy metabolism and proposed the hypothesis that obesity alters the composition of bacteria in the gut. Lipopolysaccharides (LPS) is a component of Gramnegative bacteria cell walls and is pro-inflammatory through activation of Toll-like receptor 4 (TLR4) on antigen-presenting cells located both in the gut and in other tissues in the body. Diabetes mellitus (DM) presents in two major forms: type I and type II, characterized by vastly different molecular events leading up to malfunction of glucose homeostasis.
12.	Fåk, Frida, et al. (författare) The physico-chemical properties of dietary fibre determine metabolic responses, short-chain Fatty Acid profiles and gut microbiota composition in rats fed low- and high-fat diets. 2015 Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:5 Tidskriftsartikel (refereegranskat)abstract The aim of this study was to investigate how physico-chemical properties of two dietary fibres, guar gum and pectin, affected weight gain, adiposity, lipid metabolism, short-chain fatty acid (SCFA) profiles and the gut microbiota in male Wistar rats fed either low- or high-fat diets for three weeks. Both pectin and guar gum reduced weight gain, adiposity, liver fat and blood glucose levels in rats fed a high-fat diet. Methoxylation degree of pectin (low, LM and high (HM)) and viscosity of guar gum (low, medium or high) resulted in different effects in the rats, where total blood and caecal amounts of SCFA were increased with guar gum (all viscosities) and with high methoxylated (HM) pectin. However, only guar gum with medium and high viscosity increased the levels of butyric acid in caecum and blood. Both pectin and guar gum reduced cholesterol, liver steatosis and blood glucose levels, but to varying extent depending on the degree of methoxylation and viscosity of the fibres. The medium viscosity guar gum was the most effective preparation for prevention of diet-induced hyperlipidaemia and liver steatosis. Caecal abundance of Akkermansia was increased with high-fat feeding and with HM pectin and guar gum of all viscosities tested. Moreover, guar gum had distinct bifidogenic effects independent of viscosity, increasing the caecal abundance of Bifidobacterium ten-fold. In conclusion, by tailoring the viscosity and possibly also the degree of methoxylation of dietary fibre, metabolic effects may be optimized, through a targeted modulation of the gut microbiota and its metabolites.
13.	Ghaffarzadegan, Tannaz, et al. (författare) Effects of barley variety, dietary fiber and β-glucan content on bile acid composition in cecum of rats fed low- and high-fat diets 2018 Ingår i: Journal of Nutritional Biochemistry. - : Elsevier BV. - 0955-2863. ; 53, s. 104-110 Tidskriftsartikel (refereegranskat)abstract Diet-induced obesity and insulin resistance have been linked to changes in bile acid (BA) profiles, which in turn are highly dependent on the dietary composition and activity of the gut microbiota. The objective of the present study was to investigate whether the type and level of fiber had an effect on cecal BA composition when included in low- and high-fat diets. Groups of rats were fed two barley varieties, which resulted in three test diets containing three levels of β-glucans and two levels of dietary fiber. BAs were preconcentrated using hollow fiber liquid-phase microextraction and quantified by gas chromatography. The amount of the secondary BAs, lithocholic-, deoxycholic- and hyodexycholic acids was generally higher in groups fed high-fat diets compared with corresponding acids in groups fed low-fat diets (P<.05). In contrast, most of the primary and the secondary BAs, ursodeoxycholic acid and β- and ω-muricholic acids, were two to five times higher (P<.05) in groups fed low-fat diets than in groups fed high-fat diets. This was particularly true for groups fed the highest level of β-glucans and in some cases also the medium level. The BA profile in the gut was strongly dependent on the amount and type of dietary fiber in the diet, which may be useful in the prevention/treatment of diseases associated with changes in BA profiles.
14.	Ghaffarzadegan, Tannaz, et al. (författare) Molecular properties of guar gum and pectin modify cecal bile acids, microbiota, and plasma lipopolysaccharide-binding protein in rats 2016 Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:6 Tidskriftsartikel (refereegranskat)abstract Bile acids (BAs) act as signaling molecules in various physiological processes, and are related to colonic microbiota composition as well as to different types of dietary fat and fiber. This study investigated whether guar gum and pectin-two fibers with distinct functional characteristics-affect BA profiles, microbiota composition, and gut metabolites in rats. Low- (LM) or high-methoxylated (HM) pectin, and low-, medium-, or high-molecular-weight (MW) guar gum were administered to rats that were fed either low- or high-fat diets. Cecal BAs, short-chain fatty acids (SCFA) and microbiota composition, and plasma lipopolysaccharide-binding protein (LBP) levels were analyzed, by using novel methodologies based on gas chromatography (BAs and SCFAs) and 16S rRNA gene sequencing on the Illumina MiSeq platform. Strong correlations were observed between cecal BA and SCFA levels, microbiota composition, and portal plasma LBP levels in rats on a high-fat diet. Notably, guar gum consumption with medium-MW increased the cecal amounts of cholic-, chenodeoxycholic-, and ursodeoxycholic acids as well as α-, β-, and ù-muricholic acids to a greater extent than other types of guar gum or the fiber-free control diet. In contrast, the amounts of cecal deoxycholic- and hyodeoxycholic acid were reduced with all types of guar gum independent of chain length. Differences in BA composition between pectin groups were less obvious, but cecal levels of α- and ù-muricholic acids were higher in rats fed LM as compared to HM pectin or the control diet. The inflammatory marker LBP was downregulated in rats fed medium-MW guar gum and HM pectin; these two fibers decreased the cecal abundance of Oscillospira and an unclassified genus in Ruminococcaceae, and increased that of an unclassified family in RF32. These results indicate that the molecular properties of guar gum and pectin are important for their ability to modulate cecal BA formation, gut microbiota composition, and high-fat diet induced inflammation.
15.	Graf, Daniela, et al. (författare) Contribution of diet to the composition of the human gut microbiota. 2015 Ingår i: Microbial Ecology in Health and Disease. - : Co-Action Publishing. - 0891-060X .- 1651-2235. ; 26 Tidskriftsartikel (refereegranskat)abstract In the human gut, millions of bacteria contribute to the microbiota, whose composition is specific for every individual. Although we are just at the very beginning of understanding the microbiota concept, we already know that the composition of the microbiota has a profound impact on human health. A key factor in determining gut microbiota composition is diet. Preliminary evidence suggests that dietary patterns are associated with distinct combinations of bacteria in the intestine, also called enterotypes. Western diets result in significantly different microbiota compositions than traditional diets. It is currently unknown which food constituents specifically promote growth and functionality of beneficial bacteria in the intestine. The aim of this review is to summarize the recently published evidence from human in vivo studies on the gut microbiota-modulating effects of diet. It includes sections on dietary patterns (e.g. Western diet), whole foods, food constituents, as wells as food-associated microbes and their influence on the composition of human gut microbiota. The conclusions highlight the problems faced by scientists in this fast-developing field of research, and the need for high-quality, large-scale human dietary intervention studies.
16.	Grases-Pintó, Blanca, et al. (författare) Influence of Leptin and Adiponectin Supplementation on Intraepithelial Lymphocyte and Microbiota Composition in Suckling Rats 2019 Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 10 Tidskriftsartikel (refereegranskat)abstract Dietary components in early life play a role in both microbiota and intestinal immune system maturation in mammalian species. Adipokines, as endogenously produced hormones from breast milk, may have an impact on this process. The aim of the present study was to establish the influence of leptin and adiponectin supplementation during suckling on the intraepithelial lymphocyte composition, intestinal barrier function, intestinal gene expression, and gut microbiota in rat. For this purpose, newborn Wistar rats were supplemented daily with leptin, adiponectin, or whey protein concentrate during the first 21 days of life. Lymphocyte composition was established by immunofluorescence staining and flow cytometry analysis; intestinal gene expression by real-time PCR and cecal microbiota were analyzed through 16S rRNA gene sequencing. Although leptin and adiponectin were able to increase the Tc TCRαβ+ and NKT cell proportion, they decreased the NK cell percentage in IEL. Moreover, adipokine supplementation differentially modified CD8+ IEL. While the supplementation of leptin increased the proportion of CD8αα+ IEL (associated to a more intestinal phenotype), adiponectin enhanced that of CD8αβ+ (related to a peripheral phenotype). Furthermore, both adipokines enhanced the gene expression of TNF-α, MUC-2, and MUC-3, and decreased that of FcRn. In addition, the adipokine supplementations decreased the abundance of the Proteobacteria phylum and the presence of Blautia. Moreover, leptin-supplemented animals had lower relative abundance of Sutterella and a higher proportion of Clostridium genus, among others. However, supplementation with adiponectin resulted in lower abundance of the Roseburia genus and a higher proportion of the Enterococcus genus. In conclusion, the supplementation with leptin and adiponectin throughout the suckling period had an impact on both the IEL composition and the gut microbiota pattern, suggesting a modulatory role of these adipokines on the development of intestinal functionality.
17.	Heyman Lindén, Lovisa, et al. (författare) Lingonberries alter the gut microbiota and prevent low-grade inflammation in high-fat diet fed mice 2016 Ingår i: Food & Nutrition Research. - : SNF Swedish Nutrition Foundation. - 1654-6628 .- 1654-661X. ; 60 Tidskriftsartikel (refereegranskat)abstract Background: The gut microbiota plays an important role in the development of obesity and obesity-associated impairments such as low-grade inflammation. Lingonberries have been shown to prevent diet-induced obesity and low-grade inflammation. However, it is not known whether the effect of lingonberry supplementation is related to modifications of the gut microbiota. The aim of the present study was to describe whether consumption of different batches of lingonberries alters the composition of the gut microbiota, which could be relevant for the protective effect against high fat (HF)-induced metabolic alterations. Methods: Three groups of C57BL/6J mice were fed HF diet with or without a supplement of 20% lingonberries from two different batches (Lingon1 and Lingon2) during 11 weeks. The composition and functionality of the cecal microbiota were assessed by 16S rRNA sequencing and PICRUSt. In addition, parameters related to obesity, insulin sensitivity, hepatic steatosis, inflammation and gut barrier function were examined. Results: HF-induced obesity was only prevented by the Lingon1 diet, whereas both batches of lingonberries reduced plasma levels of markers of inflammation and endotoxemia (SAA and LBP) as well as modified the composition and functionality of the gut microbiota, compared to the HF control group. The relative abundance of Akkermansia and Faecalibacterium, genera associated with healthy gut mucosa and antiinflammation, was found to increase in response to lingonberry intake. Conclusions: Our results show that supplementation with lingonberries to an HF diet prevents low-grade inflammation and is associated with significant changes of the microbiota composition. Notably, the antiinflammatory properties of lingonberries seem to be independent of effects on body weight gain.
18.	Huang, Fang, et al. (författare) Identification of Nordic Berries with Beneficial Effects on Cognitive Outcomes and Gut Microbiota in High-Fat-Fed Middle-Aged C57BL/6J Mice 2022 Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 14:13 Tidskriftsartikel (refereegranskat)abstract High-fat diets are associated with neuronal and memory dysfunction. Berries may be useful in improving age-related memory deficits in humans, as well as in mice receiving high-fat diets. Emerging research has also demonstrated that brain health and cognitive function may be related to the dynamic changes in the gut microbiota. In this study, the impact of Nordic berries on the brain and the gut microbiota was investigated in middle-aged C57BL/6J mice. The mice were fed high-fat diets (60%E fat) supplemented with freeze-dried powder (6% dwb) of bilberry, lingonberry, cloudberry, blueberry, blackcurrant, and sea buckthorn for 4 months. The results suggest that supplementation with bilberry, blackcurrant, blueberry, lingonberry, and (to some extent) cloudberry has beneficial effects on spatial cognition, as seen by the enhanced performance following the T-maze alternation test, as well as a greater proportion of DCX-expressing cells with prolongation in hippocampus. Furthermore, the proportion of the mucosa-associated symbiotic bacteria Akkermansia muciniphila increased by 4-14 times in the cecal microbiota of mice fed diets supplemented with lingonberry, bilberry, sea buckthorn, and blueberry. These findings demonstrate the potential of Nordic berries to preserve memory and cognitive function, and to induce alterations of the gut microbiota composition.
19.	Jakobsdottir, Greta, et al. (författare) Designing future prebiotic fiber to target the metabolic syndrome. 2014 Ingår i: Nutrition. - : Elsevier BV. - 1873-1244 .- 0899-9007. ; 30:5, s. 497-502 Forskningsöversikt (refereegranskat)abstract The metabolic syndrome (MetS), characterized by obesity, hyperlipidemia, hypertension, and insulin resistance, is a growing epidemic worldwide, requiring new prevention strategies and therapeutics. The concept of prebiotics refers to selective stimulation of growth and/or activity(ies) of one or a limited number of microbial genus(era)/species in the gut microbiota that confer(s) health benefits to the host. Sequencing the gut microbiome and performing metagenomics has provided new knowledge of the significance of the composition and activity of the gut microbiota in metabolic disease. As knowledge of how a healthy gut microbiota is composed and which bacterial metabolites are beneficial increases, tailor-made dietary interventions using prebiotic fibers could be developed for individuals with MetS. In this review, we describe how dietary fibers alter short-chain fatty acid (SCFA) profiles and the intrinsic and extrinsic effects of prebiotics on host metabolism. We focus on several key aspects in prebiotic research in relation to MetS and provide mechanistic data that support the use of prebiotic fibers in order to alter the gut microbiota composition and SCFA profiles. Further studies in the field should provide reliable mechanistic and clinical evidence for how prebiotics can be used to alleviate MetS and its complications. Additionally, it will be important to clarify the effect of individual differences in the gut microbiome on responsiveness to prebiotic interventions.
20.	Karlsson, Fredrik, 1984, et al. (författare) Symptomatic atherosclerosis is associated with an altered gut metagenome 2012 Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 3 Tidskriftsartikel (refereegranskat)abstract Recent findings have implicated the gut microbiota as a contributor of metabolic diseases through the modulation of host metabolism and inflammation. Atherosclerosis is associated with lipid accumulation and inflammation in the arterial wall, and bacteria have been suggested as a causative agent of this disease. Here we use shotgun sequencing of the gut metagenome to demonstrate that the genus Collinsella was enriched in patients with symptomatic atherosclerosis, defined as stenotic atherosclerotic plaques in the carotid artery leading to cerebrovascular events, whereas Roseburia and Eubacterium were enriched in healthy controls. Further characterization of the functional capacity of the metagenomes revealed that patient gut metagenomes were enriched in genes encoding peptidoglycan synthesis and depleted in phytoene dehydrogenase; patients also had reduced serum levels of β-carotene. Our findings suggest that the gut metagenome is associated with the inflammatory status of the host and patients with symptomatic atherosclerosis harbor characteristic changes in the gut metagenome.
21.	Koren, Omry, et al. (författare) Microbes and Health Sackler Colloquium: Human oral, gut, and plaque microbiota in patients with atherosclerosis. 2011 Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 108:Suppl 1, s. 4592-4598 Tidskriftsartikel (refereegranskat)abstract Periodontal disease has been associated with atherosclerosis, suggesting that bacteria from the oral cavity may contribute to the development of atherosclerosis and cardiovascular disease. Furthermore, the gut microbiota may affect obesity, which is associated with atherosclerosis. Using qPCR, we show that bacterial DNA was present in the atherosclerotic plaque and that the amount of DNA correlated with the amount of leukocytes in the atherosclerotic plaque. To investigate the microbial composition of atherosclerotic plaques and test the hypothesis that the oral or gut microbiota may contribute to atherosclerosis in humans, we used 454 pyrosequencing of 16S rRNA genes to survey the bacterial diversity of atherosclerotic plaque, oral, and gut samples of 15 patients with atherosclerosis, and oral and gut samples of healthy controls. We identified Chryseomonas in all atherosclerotic plaque samples, and Veillonella and Streptococcus in the majority. Interestingly, the combined abundances of Veillonella and Streptococcus in atherosclerotic plaques correlated with their abundance in the oral cavity. Moreover, several additional bacterial phylotypes were common to the atherosclerotic plaque and oral or gut samples within the same individual. Interestingly, several bacterial taxa in the oral cavity and the gut correlated with plasma cholesterol levels. Taken together, our findings suggest that bacteria from the oral cavity, and perhaps even the gut, may correlate with disease markers of atherosclerosis.
22.	Kostiuchenko, Olha, et al. (författare) Effects of Proteases from Pineapple and Papaya on Protein Digestive Capacity and Gut Microbiota in Healthy C57BL/6 Mice and Dose-Manner Response on Mucosal Permeability in Human Reconstructed Intestinal 3D Tissue Model 2022 Ingår i: Metabolites. - : MDPI AG. - 2218-1989. ; 12:11, s. 1-15 Tidskriftsartikel (refereegranskat)abstract Cysteine proteases obtained from the stem of pineapple or papaya latex, bromelain and papain, respectively, exhibit a broad spectrum of beneficial effects on human health. However, their effects on gut microbiota composition or dose-manner effects on the intestinal integrity of healthy tissue have not been evaluated. In this study, C57BL/6 young, healthy mice were fed bromelain or papain in a dose of 1 mg per animal/day for three consecutive days, followed by the assessment of digestive protein capacity, intestinal morphology and gut microbiota composition. Furthermore, a human reconstructed 3D tissue model EpiIntestinal (SMI-100) was used to study the effects of 1, 0.1 and 10 mg/mL doses of each enzyme on tissue integrity and mucosal permeability using TEER measurements and passage of Lucifer Yellow marker from the apical to the basolateral side of the mucosa. The results indicated that fruit proteases have the potential to modulate gut microbiota with decreasing abundance of Proteobacteria and increasing beneficial Akkermansia muciniphila. The enhancement of pancreatic trypsin was observed in bromelain and papain supplementation, while bromelain also increased the thickness of the ileal mucosa. Furthermore, an in vitro study showed a dose-dependent interruption in epithelial integrity, which resulted in increased paracellular permeability by the highest doses of enzymes. These findings define bromelain and papain as promising enzymatic supplementation for controlled enhancement of paracellular uptake when needed, together with beneficial effects on the gut microbiota.
23.	Lavasani, Shahram, et al. (författare) A novel probiotic mixture exerts a therapeutic effect on experimental autoimmune encephalomyelitis mediated by IL-10 producing regulatory T cells. 2010 Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:2 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). One potential therapeutic strategy for MS is to induce regulatory cells that mediate immunological tolerance. Probiotics, including lactobacilli, are known to induce immunomodulatory activity with promising effects in inflammatory diseases. We tested the potential of various strains of lactobacilli for suppression of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. METHODOLOGY/PRINCIPAL FINDINGS: The preventive effects of five daily-administered strains of lactobacilli were investigated in mice developing EAE. After a primary screening, three Lactobacillus strains, L. paracasei DSM 13434, L. plantarum DSM 15312 and DSM 15313 that reduced inflammation in CNS and autoreactive T cell responses were chosen. L. paracasei and L. plantarum DSM 15312 induced CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) in mesenteric lymph nodes (MLNs) and enhanced production of serum TGF-beta1, while L. plantarum DSM 15313 increased serum IL-27 levels. Further screening of the chosen strains showed that each monostrain probiotic failed to be therapeutic in diseased mice, while a mixture of the three lactobacilli strains suppressed the progression and reversed the clinical and histological signs of EAE. The suppressive activity correlated with attenuation of pro-inflammatory Th1 and Th17 cytokines followed by IL-10 induction in MLNs, spleen and blood. Additional adoptive transfer studies demonstrated that IL-10 producing CD4(+)CD25(+) Tregs are involved in the suppressive effect induced by the lactobacilli mixture. CONCLUSIONS/SIGNIFICANCE: Our data provide evidence showing that the therapeutic effect of the chosen mixture of probiotic lactobacilli was associated with induction of transferable tolerogenic Tregs in MLNs, but also in the periphery and the CNS, mediated through an IL-10-dependent mechanism. Our findings indicate a therapeutic potential of oral administration of a combination of probiotics and provide a more complete understanding of the host-commensal interactions that contribute to beneficial effects in autoimmune diseases.
24.	Linderoth, Ann, et al. (författare) Binding and the effect of the red kidney bean lectin, phytohaemagglutinin, in the gastrointestinal tract of suckling rats 2006 Ingår i: British Journal of Nutrition. - 1475-2662. ; 95:1, s. 105-115 Tidskriftsartikel (refereegranskat)abstract Enteral exposure of suckling rats to phytohaemagglutinin (PHA) has been shown to induce growth and precocious functional maturation of the gastrointestinal tract. The aim of the present study was to explore the mechanism of this action. Suckling rats, 14 d old, were fed a single dose of PHA (0.05 mg/g body weight) or saline. The binding of PHA to the gut epithelium and its effect on the morphology and functional properties of the gut and pancreas were studied up to 3 d after treatment. Initially, at 1-24 h, the PHA bound along the gut mucosal lining, resulting in disturbed gut morphology with villi shortening and rapid decreases in disaccharidase activities and macromolecular absorption capacity. During a later phase, between 1 and 3 d, the PHA binding had declined, and an uptake by enterocytes was observed. An increase in crypt cell proliferation and gut growth became evident during this period, together with a functional maturation, as indicated by increases in disaccharidase (maltase and sucrase) activities and the low macromolecular absorption capacity. Pancreas growth also increased, as did its content of digestive enzymes. We conclude that enteral exposure to PHA in suckling rats temporarily causes mucosal disarrangement and functional impediment of the gut, which may be explained by binding to and disruption of the gut mucosa and a two-fold increase in the plasma corticosterone concentration. These findings may lead to a better understanding of the role of diet in gastrointestinal maturation and may constitute a basis for the treatment of mammals having an immature gut.
25.	Lindskog Jonsson, Annika, et al. (författare) Bacterial profile in human atherosclerotic plaques 2017 Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 263, s. 177-183 Tidskriftsartikel (refereegranskat)abstract Background and aims Several studies have confirmed the presence of bacterial DNA in atherosclerotic plaques, but its contribution to plaque stability and vulnerability is unclear. In this study, we investigated whether the bacterial plaque-profile differed between patients that were asymptomatic or symptomatic and whether there were local differences in the microbial composition within the plaque. Methods Plaques were removed by endarterectomy from asymptomatic and symptomatic patients and divided into three different regions known to show different histological vulnerability: A, upstream of the maximum stenosis; B, site for maximum stenosis; C, downstream of the maximum stenosis. Bacterial DNA composition in the plaques was determined by performing 454 pyrosequencing of the 16S rRNA genes, and total bacterial load was determined by qPCR. Results We confirmed the presence of bacterial DNA in the atherosclerotic plaque by qPCR analysis of the 16S rRNA gene but observed no difference (n.s.) in the amount between either asymptomatic and symptomatic patients or different plaque regions A, B and C. Unweighted UniFrac distance metric analysis revealed no distinct clustering of samples by patient group or plaque region. Operational taxonomic units (OTUs) from 5 different phyla were identified, with the majority of the OTUs belonging to Proteobacteria (48.3%) and Actinobacteria (40.2%). There was no difference between asymptomatic and symptomatic patients, or plaque regions, when analyzing the origin of DNA at phylum, family or OTU level (n.s.). Conclusions There were no major differences in bacterial DNA amount or microbial composition between plaques from asymptomatic and symptomatic patients or between different plaque regions, suggesting that other factors are more important in determining plaque vulnerability. © 2017 Elsevier B.V.

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