Long-Term Changes to the Microbiome, Blood Lipid Profiles and IL-6 in Female and Male Swedish Patients in Response to Bariatric Roux-en-Y Gastric Bypass.

Lipid metabolism dysregulation is a critical factor contributing to obesity. To counteract obesity-associated disorders, bariatric surgery is implemented as a very effective method. However, surgery such as Roux-en-Y gastric bypass (RYGB) is irreversible, resulting in life-long changes to the digestive tract. The aim of the present study was to elucidate changes in the fecal microbiota before and after RYGB in relation to blood lipid profiles and proinflammatory IL-6. Here, we studied the long-term effects, up to six years after the RYGB procedure, on 15 patients' gut microbiomes and their post-surgery well-being, emphasizing the biological sex of the patients. The results showed improved health among the patients after surgery, which coincided with weight loss and improved lipid metabolism. Health changes were associated with decreased inflammation and significant alterations in the gut microbiome after surgery that differed between females and males. The Actinobacteriota phylum decreased in females and increased in males. Overall increases in the genera Prevotella, Paraprevotella, Gemella, Streptococcus, and Veillonella_A, and decreases in Bacteroides_H, Anaerostipes, Lachnoclostridium_B, Hydrogeniiclostridium, Lawsonibacter, Paludicola, and Rothia were observed. In conclusion, our findings indicate that there were long-term changes in the gut microbiota after RYGB, and shifts in the microbial taxa appeared to differ depending on sex, which should be investigated further in a larger cohort.

Monobutyrin and monovalerin improve gut-blood-brain biomarkers and alter gut microbiota composition in high-fat fed apolipoprotein-E-knockout rats.

Monobutyrin (MB) and monovalerin (MV), glycerol esters of short-chain fatty acids (SCFAs), have been shown to positively influence lipid profile and biomarkers in the gut and brain. This study examined whether MB and MV in high-fat diets, affected microbiota composition and gut-blood-brain markers in apolipoprotein E deficient (ApoE-/-) rats, a model for studies of lipid-associated disorders, and neurodegenerative processes in Alzheimer's disease (AD). ApoE-/- rats fed MB and MV increased Tenericutes and the brain neurotransmitter γ-aminobutyric acid (GABA), while the blood stress hormone corticosterone decreased compared to control rats. Only rats that received MB showed a significant increase in cholic acid and Adlercreutzia in the caecum. In rats fed MV, the decrease of Proteobacteria was associated with decreased corticosterone levels. Conclusively, dietary supplementation of SCFA glycerol esters can modulate gut-blood-brain markers and alter gut microbiota composition in ApoE-/- rats, suggesting that SCFAs also could counteract lipid disorders-related diseases.

Identification of Nordic Berries with Beneficial Effects on Cognitive Outcomes and Gut Microbiota in High-Fat-Fed Middle-Aged C57BL/6J Mice.

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.

Monobutyrin and Monovalerin Affect Brain Short-Chain Fatty Acid Profiles and Tight-Junction Protein Expression in ApoE-Knockout Rats Fed High-Fat Diets.

Monobutyrin (MB) and monovalerin (MV), esters of short-chain fatty acids (SCFAs), have previously been shown to reduce liver cholesterol and inflammation in conventional rats fed high-fat diets. This study explored the potential effects of MB and MV in hypercholesterolemic apolipoprotein E-knockout (ApoE-/-) rats. ApoE-/- rats were fed three high-fat (HF) diets, pure or supplemented with MB or MV (1%), for 5 weeks. One group of conventional rats (C) was also fed the pure high-fat diet and another group of ApoE-/- rats a low-fat (LF) diet. Blood and liver lipids, urinary lactulose/mannitol, SCFAs (blood and brain), tight junction proteins (small intestine and brain), and inflammation-related markers (blood, brain, and liver) were analyzed. MV supplementation elevated serum high-density lipoprotein (HDL) cholesterol and valeric acid concentration (p < 0.05), while the amounts of isovaleric acid in the brain were reduced (p < 0.05). MB increased butyric acid amounts in the brain, while the plasma concentration of interleukin 10 (IL-10) was lowered (p < 0.05). Both MV and MB upregulated the expression of occludin and zonula occludens-1 (ZO-1) in the brain (p < 0.05). Supplementation of MB or MV affected HDL cholesterol, the expression of tight junction proteins, and SCFA profiles. MB and MV may therefore be promising supplements to attenuate lipid metabolic disorders caused by high-fat intake and genetic deficiency.

Lingonberries and their two separated fractions differently alter the gut microbiota, improve metabolic functions, reduce gut inflammatory properties, and improve brain function in ApoE-/- mice fed high-fat diet.

Lingonberries (LB) have been shown to have beneficial metabolic effects, which is associated with an altered gut microbiota. This study investigated whether the LB-induced improvements were associated with altered gut- and neuroinflammatory markers, as well as cognitive performance in ApoE-/- mice fed high-fat (HF) diets. Whole LB, as well as two separated fractions of LB were investigated. Eight-week-old male ApoE-/- mice were fed HF diets (38% kcal) containing whole LB (wLB), or the insoluble (insLB) and soluble fractions (solLB) of LB for 8 weeks. Inclusion of wLB and insLB fraction reduced weight gain, reduced fat deposition and improved glucose response. Both wLB and insLB fraction also changed the caecal microbiota composition and reduced intestinal S100B protein levels. The solLB fraction mainly induced weight loss in the mice. There were no significant changes in spatial memory, but significant increases in synaptic density in the hippocampus were observed in the brain of mice-fed wLB and insLB. Thus, this study shows that all lingonberry fractions counteracted negative effects of HF feedings on metabolic parameters. Also, wLB and insLB fraction showed to potentially improve brain function in the mice.

Determination of free and conjugated bile acids in serum of Apoe(-/-) mice fed different lingonberry fractions by UHPLC-MS.

Bile acids (BAs) are known to be involved in cholesterol metabolism but interactions between the diet, BA profiles, gut microbiota and lipid metabolism have not been extensively explored. In the present study, primary and secondary BAs including their glycine and taurine-conjugated forms were quantified in serum of Apoe-/- mice by protein precipitation followed by reversed phase ultra-high-performance liquid chromatography and QTOF mass spectrometry. The mice were fed different lingonberry fractions (whole, insoluble and soluble) in a high-fat setting or cellulose in a high and low-fat setting. Serum concentrations of BAs in mice fed cellulose were higher with the high-fat diet compared to the low-fat diet (20-70%). Among the lingonberry diets, the diet containing whole lingonberries had the highest concentration of chenodeoxycholic acid (CDCA), ursodeoxycholic acid (UDCA), tauro-ursodeoxycholic acid (T-UDCA), α and ω-muricholic acids (MCA) and tauro-α-MCA (T-α-MCA), and the lowest concentration of tauro-cholic acid (T-CA), deoxycholic acid (DCA) and tauro-deoxycholic acid (T-DCA). The glycine-conjugated BAs were very similar with all diets. CDCA, UDCA and α-MCA correlated positively with Bifidobacterium and Prevotella, and T-UDCA, T-α-MCA and ω-MCA with Bacteroides and Parabacteroides.

Improvement in cardiometabolic risk markers following a multifunctional diet is associated with gut microbial taxa in healthy overweight and obese subjects.

PURPOSE: A multifunctional diet (MFD) targeting subclinical inflammation was developed as a tool to decrease risk factors for cardiometabolic disease in healthy "at-risk" individuals (BMI 25-33 kg/m2). MFD contains several components that are degraded in the colon by the microbiota, such as dietary fibers from rye, barley, oats and berries. It also contains soy beans, oily fish and plant stanols. In previous studies, we have observed improved cardiometabolic markers in healthy at-risk individuals after 4-8 week intake of MFD. However, whether these improvements can be associated with changes in the gut microbiota composition has not been investigated. In the present study, we analyzed the gut microbiota before and after an 8-week dietary intervention with MFD. METHODS: Cardiometabolic at-risk individuals (n = 47), between 51 and 72 years old and with a BMI of 25-33 kg/m2, were given either the MFD or a control diet lacking the functional ("active") components for 8 weeks in a parallel, randomized design. Next-generation sequencing of bacterial 16S rRNA genes was used to analyze the gut microbiota composition. RESULTS: The 8-week intervention with MFD did not significantly alter the gut microbiota composition at phylum or genus taxonomic levels, while LEfSE analysis identified increased abundance of Prevotella copri in the MFD group as compared to the control group. Treponema correlated positively with blood pressure. In contrast, Faecalibacterium showed a negative association with blood pressure, while Bilophila appeared to associate with a negative blood lipid profile. CONCLUSIONS: Taken together, results from the present study may be used in the further development of effective dietary concepts capable of reducing cardiometabolic risk markers in humans through a targeted modulation of the gut microbial community. TRIAL REGISTRATION NUMBER: Clinical Trials.gov NCT02148653.

Bacterial profile in human atherosclerotic plaques.

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.