Gut Microbial Activity Research Articles

Fecal microbiome and metabolome of infants fed bovine MFGM supplemented formula or standard formula with breast-fed infants as reference: a randomized controlled trial

Human milk delivers an array of bioactive components that safeguard infant growth and development and maintain healthy gut microbiota. Milk fat globule membrane (MFGM) is a biologically functional fraction of milk increasingly linked to beneficial outcomes in infants through protection from pathogens, modulation of the immune system and improved neurodevelopment. In the present study, we characterized the fecal microbiome and metabolome of infants fed a bovine MFGM supplemented experimental formula (EF) and compared to infants fed standard formula (SF) and a breast-fed reference group. The impact of MFGM on the fecal microbiome was moderate; however, the fecal metabolome of EF-fed infants showed a significant reduction of several metabolites including lactate, succinate, amino acids and their derivatives from that of infants fed SF. Introduction of weaning food with either human milk or infant formula reduces the distinct characteristics of breast-fed- or formula-fed- like infant fecal microbiome and metabolome profiles. Our findings support the hypothesis that higher levels of protein in infant formula and the lack of human milk oligosaccharides promote a shift toward amino acid fermentation in the gut. MFGM may play a role in shaping gut microbial activity and function.

Effects of Gut Microbiota on the Bioavailability of Bioactive Compounds from Ginkgo Leaf Extracts.

Ginkgo leaf extract (GLE) is a popular herbal medicine and dietary supplement for the treatment of various diseases, including cardiovascular disease. GLE contains a variety of secondary plant metabolites, such as flavonoids and terpenoids, as active components. Some of these phytochemicals have been known to be metabolized by gut microbial enzymes. The aim of this study was to investigate the effects of the gut microbiota on the pharmacokinetics of the main constituents of GLE using antibacterial-treated mice. The bilobalide, ginkgolide A, ginkgolide B, ginkgolide C, isorhamnetin, kaempferol, and quercetin pharmacokinetic profiles of orally administered GLE (600 mg/kg), with or without ciprofloxacin pretreatment (150 mg/kg/day for 3 days), were determined. In the antibacterial-treated mice, the maximum plasma concentration (Cmax) and area under the curve (AUC) of isorhamnetin were significantly (p < 0.05) increased when compared with the control group. The Cmax and AUC of kaempferol and quercetin (other flavonol glycosides) were slightly higher than those of the control group, but the difference was not statistically significant, while both parameters for terpenoids of GLE showed no significant difference between the antibacterial-treated and control groups. These results showed that antibacterial consumption may increase the bioavailability of isorhamnetin by suppressing gut microbial metabolic activities.

Metabolic Fate and Distribution of 2´-Fucosyllactose: Direct Influence on Gut Microbial Activity but not on Brain.

Scope2´‐Fucosyllactose (2´FL) is an abundant oligosaccharide in human milk. It is hypothesized that its brain enrichment is associated with improved learning. Accumulation of 2´FL in organs, biological fluids, and feces is assessed in wild‐type and germ‐free mice.Methods and results 13C‐labelled 2´FL is applied to NMRI wild‐type mice intravenously (0.2 g kg−1) or orally (1 g kg−1), while controls receive saline. Biological samples are collected (0.5–15 h) and 13C‐enrichment is measured by elemental analysis isotope ratio mass spectrometry (EA‐IRMS). After oral application, 2´FL is primarily eliminated in the feces. 13C‐enrichment in organs including the brain follows the same pattern as in plasma with a maximum peak after 5 h. However, 13C‐enrichment is only detected when the 13C‐2´FL bolus reaches the colon. In contrast, in germ‐free mice, the 13C‐bolus remains in the intestinal content and is expelled via the feces. Furthermore, intravenously applied 13C‐2´FL is eliminated via urine; no 13C‐enrichment of organs is observed, suggesting that intact 2´FL is not retained.Conclusions 13C‐enrichment in brain and other organs after oral application of 13C‐2´FL in wild‐type mice indicates cleaved fucose or other gut microbial 2´FL metabolites may be incorporated, as opposed to intact 2´FL.

Gut microbial beta-glucuronidase and glycerol/diol dehydratase activity contribute to dietary heterocyclic amine biotransformation

BackgroundConsuming red and processed meat has been associated with an increased risk of colorectal cancer (CRC), which is partly attributed to exposure to carcinogens such as heterocyclic amines (HCA) formed during cooking and preservation processes. The interaction of gut microbes and HCA can result in altered bioactivities and it has been shown previously that human gut microbiota can transform mutagenic HCA to a glycerol conjugate with reduced mutagenic potential. However, the major form of HCA in the colon are glucuronides (HCA-G) and it is not known whether these metabolites, via stepwise microbial hydrolysis and acrolein conjugation, are viable precursors for glycerol conjugated metabolites. We hypothesized that such a process could be concurrently catalyzed by bacterial beta-glucuronidase (B-GUS) and glycerol/diol dehydratase (GDH) activity. We therefore investigated how the HCA-G PhIP-N2-β-D-glucuronide (PhIP-G), a representative liver metabolite of PhIP (2-Amino-1-methyl-6-phenylimidazo [4,5-b] pyridine), which is the most abundant carcinogenic HCA in well-cooked meat, is transformed by enzymatic activity of human gut microbial representatives of the phyla Firmicutes, Bacteroidetes, and Proteobacteria.ResultsWe employed a combination of growth and enzymatic assays, and a bioanalysis approach combined with metagenomics. B-GUS of Faecalibacterium prausnitzii converted PhIP-G to PhIP and GDH of Flavonifractor plautii, Blautia obeum, Eubacterium hallii, and Lactobacillus reuteri converted PhIP to PhIP-M1 in the presence of glycerol. In addition, B-GUS- and GDH-positive bacteria cooperatively converted PhIP-G to PhIP-M1. A screen of genes encoding B-GUS and GDH was performed for fecal microbiome data from healthy individuals (n = 103) and from CRC patients (n = 53), which revealed a decrease in abundance of taxa with confirmed GDH and HCA transformation activity in CRC patients.ConclusionsThis study for the first time demonstrates that gut microbes mediate the stepwise transformation of PhIP-G to PhIP-M1 via the intermediate production of PhIP. Findings from this study suggest that targeted manipulation with gut microbes bearing specific functions, or dietary glycerol supplementation might modify gut microbial activity to reduce HCA-induced CRC risk.

OR31-3 Role of a Novel Short Chain Fatty Acid Receptor OLFR78 in Mediating Gluco-metabolic Hormone Secretion

Olfactory receptor OLFR78 is a G protein-coupled receptor (GPCR) which is activated by short chain fatty acids (SCFAs), especially propionate. OLFR78 is expressed in islets as well as intestinal epithelial cells. Based on these properties, we hypothesized its role in the regulation of metabolic hormone secretion. Our emerging data shows that OLFR78 signaling regulates GLP-1 secretion from murine enteroendocrine cells in vitro and ex vivo. We demonstrate that knockdown of Olfr78 through siRNA in the murine enteroendocrine cell line STC-1 results in a significant reduction in propionate-induced GLP-1 secretion. Utilizing constitutive and cyclic AMP inducible transcriptional luciferase promoters in addition to G protein pathway modulators, we further demonstrate that the signaling pathway downstream of active OLFR78 involves the activation of a Gαs subunit. As GLP-1 is an insulinotropic factor, we sought to determine the role of OLFR78 in insulin secretion and β cell mass maintenance. Using islets isolated from both wildtype and global OLFR78 knockout mice, we show that OLFR78 signaling in islets does not have a significant effect on insulin secretion. Additionally, we observed no differences in beta cell mass in wildtype versus OLFR78 knockout mice. Furthermore, no differences are observed in incretin secretion in response to oral glucose challenge between wildtype and knockout mice fed normal chow. However, ileal explants prepared from wildtype mice reveal higher secretion of GLP-1 in response to propionate challenge. These data suggest that specific activation of the receptor, rather than its presence alone, affects GLP-1 secretion. We have previously shown that the activity of other SCFA-sensing GPCRs, such as FFA2 and FFA3, are dependent on gut microbiota-derived metabolites which fluctuate with physiological stress. Similarly, we believe that the function of OLFR78 will be more evident under conditions of dietary stress, which is a crucial determinant of gut microbial activity.

Potential Role for the Gut Microbiota in Modulating Host Circadian Rhythms and Metabolic Health.

This article reviews the current evidence associating gut microbiota with factors that impact host circadian-metabolic axis, such as light/dark cycles, sleep/wake cycles, diet, and eating patterns. We examine how gut bacteria possess their own daily rhythmicity in terms of composition, their localization to intestinal niches, and functions. We review evidence that gut bacteria modulate host rhythms via microbial metabolites such as butyrate, polyphenolic derivatives, vitamins, and amines. Lifestyle stressors such as altered sleep and eating patterns that may disturb the host circadian system also influence the gut microbiome. The consequent disruptions to microbiota-mediated functions such as decreased conjugation of bile acids or increased production of hydrogen sulfide and the resultant decreased production of butyrate, in turn affect substrate oxidation and energy regulation in the host. Thus, disturbances in microbiome rhythms may at least partially contribute to an increased risk of obesity and metabolic syndrome associated with insufficient sleep and circadian misalignment. Good sleep and a healthy diet appear to be essential for maintaining gut microbial balance. Manipulating daily rhythms of gut microbial abundance and activity may therefore hold promise for a chrononutrition-based approach to consolidate host circadian rhythms and metabolic homeorhesis.

The Effect of Gluten-Free Diet on Health and the Gut Microbiota Cannot Be Extrapolated from One Population to Others.

Gluten-related disorders (GRD) affect millions of people worldwide and have been related to the composition and metabolism of the gut microbiota. These disorders present differently in each patient and the only treatment available is a strict life-long gluten-free diet (GFD). Several studies have investigated the effect of a GFD on the gut microbiota of patients afflicted with GRD as well as healthy people. The purpose of this review is to persuade the biomedical community to think that, while useful, the results from the effect of GFD on health and the gut microbiota cannot be extrapolated from one population to others. This argument is primarily based on the highly individualized pattern of gut microbial composition and metabolic activity in each person, the variability of the gut microbiota over time and the plethora of factors associated with this variation. In addition, there is wide variation in the composition, economic viability, and possible deleterious effects to health among different GFD, both within and among countries. Overall, this paper encourages the conception of more collaborative efforts to study local populations in an effort to reach biologically and medically useful conclusions that truly contribute to improve health in patients afflicted with GRD.

Abstract 3265: Healthy eating index 2005 and the mucosa associated gut microbiome in healthy individuals

Abstract Background: Diet is a modifiable risk factor for multiple cancers. It is also known to modulate gut microbial composition and metabolic activity, and plays an important role in maintaining gut homeostasis. However, our understanding of dietary quality and mucosa-associated microbiota in the large intestine in humans is limited. We examined the association between diet quality and gut microbiota in adults underwent routine colonoscopy in a cross-sectional study. Methods: We enrolled 21 men (50-75 years old, 71% White) who were found to have grossly normal colons at colonoscopy completed between July 2013 and April 2016. We obtained 98 colonic mucosa biopsies, with microbial DNA extracted from snap frozen biopsy. The 16S rRNA V4 region was amplified and sequenced on the Illumina MiSeq platform. The UPARSE and SILVA were used for operational taxonomic unit (OTU) classification. A self-administered BLOCK Food Frequency Questionnaire was used to assess dietary intake in the past year. Dietary quality was defined using the Healthy Eating Index (HEI)-2005, and further categorized as low or high using the median of total HEI or 12 individual component scores. We compared alpha-diversity (OTU and Shannon index), beta-diversity (Weighted UniFrac principal coordinates analysis), and relative abundance of bacterial phylum and genus by total HEI and all 12 individual HEI components using Mann-Whitney test. Reported P values were adjusted for multiple testing using false discovery rate. Results: The most abundant bacterial phyla observed were Firmicutes, Bacteroidetes, Proteobacteria, Verrucomicrobia, and Fusobacteria. High-quality diet (total HEI score ≥ 63) was not associated with higher richness and evenness of gut microbiome (P = 0.12), but was significantly associated with bacterial composition (P = 0.046). Compared to men who had low-quality diet (total HEI score &amp;lt; 63), those with high-quality diet had a higher abundance of Proteobacteria (12.2% vs. 8.1%, P = 0.006), and lower abundance of Fusobacteria (0.13% vs. 3.37%, P = 0.004). At the genus level, those with high-quality diet had significantly lower abundance of Fusobacterium than those with low-quality diet (0.11% vs. 3.77%, P = 0.004). At the HEI component level, individuals with a higher consumption of solid fruits and milk had higher richness and evenness of gut microbiome (P &amp;lt; 0.05) as well as higher abundance of phylum Verrucomicrobia (P &amp;lt; 0.05) and genus Akkermansia (P &amp;lt; 0.001). Consuming more solid and saturated fat, alcohol, and added sugar were associated with a higher abundance of phylum Fusobacteria (P &amp;lt; 0.0001) and genus Fusobacterium (P = 0.0001). Conclusions: The colonic microbiome of men consuming a low-quality diet exhibited increased levels of Fusobacteria, which has been associated with colorectal cancer risk. If replicated in prospective research, our findings suggest low quality diet may contribute to colorectal cancer by modulating gut microbiome. Citation Format: Yanhong Liu, Nadim J. Ajami, Diane Hutchinson, David Graham, Sarah Plew, Ashley Johnson, Preksha Shah, Liang Chen, Kathryn Royse, Donna L. White, Jennifer Kramer, Matthew C. Wong, Rhonda Cole, Clark Hair, Jason Hou, Nisreen Husain, Maria Jarbrink-Sehgal, Fasiha Kanwal, Gyanprakash Ketwaroo, Rajesh Shah, Maria Velez, Melissa L. Bondy, Hashem B. El-Serag, Joseph F. Petrosino, Li Jiao. Healthy eating index 2005 and the mucosa associated gut microbiome in healthy individuals [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3265.

Long-Term Administration of Conjugated Estrogen and Bazedoxifene Decreased Murine Fecal \u03b2-Glucuronidase Activity Without Impacting Overall Microbiome Community

Conjugated estrogens (CE) and Bazedoxifene (BZA) combination is used to alleviate menopause-associated symptoms in women. CE+BZA undergo first-pass-metabolism in the liver and deconjugation by gut microbiome via β-glucuronidase (GUS) enzyme inside the distal gut. To date, the impact of long-term exposure to CE+BZA on the gut microbiome or GUS activity has not been examined. Our study using an ovariectomized mouse model showed that CE+BZA administration did not affect the overall cecal or fecal microbiome community except that it decreased the abundance of Akkermansia, which was identified as a fecal biomarker correlated with weight gain. The fecal GUS activity was reduced significantly and was positively correlated with the abundance of Lactobacillaceae in the fecal microbiome. We further confirmed in Escherichia coli K12 and Lactobacillus gasseri ADH that Tamoxifen-, 4-hydroxy-Tamoxifen- and Estradiol-Glucuronides competed for GUS activity. Our study for the first time demonstrated that long-term estrogen supplementation directly modulated gut microbial GUS activity. Our findings implicate that long-term estrogen supplementation impacts composition of gut microbiota and microbial activity, which affects estrogen metabolism in the gut. Thus, it is possible to manipulate such activity to improve the efficacy and safety of long-term administered estrogens for postmenopausal women or breast cancer patients.

Gut Microbiota: FFAR Reaching Effects on Islets.

The G protein-coupled receptors, free fatty acid (FFA) receptors 2 and 3 (FFA2 and FFA3), belonging to the free fatty acid receptor (FFAR) class, sense a distinct class of nutrients, short chain fatty acids (SCFAs). These receptors participate in both immune and metabolic regulation. The latter includes a role in regulating secretion of metabolic hormones. It was only recently that their role in pancreatic β cells was recognized; these receptors are known now to affect not only insulin secretion but also β-cell survival and proliferation. These observations make them excellent potential therapeutic targets in type 2 diabetes. Moreover, expression on both immune and β cells makes these receptors possible targets in type 1 diabetes. Furthermore, SCFAs are generated by gut microbial fermentative activity; therefore, signaling by FFA2 and FFA3 represents an exciting novel link between the gut microbiota and the β cells. This review enumerates the role of these receptors in β cells revealed so far and discusses possible roles in clinical translation.

Arabinoxylo-Oligosaccharides and Inulin Impact Inter-Individual Variation on Microbial Metabolism and Composition, Which Immunomodulates Human Cells.

Fecal batch fermentations coupled to cocultures of epithelial cells and macrophages were used to compare how arabinoxylo-oligosaccharides (AXOS) and inulin modulate gut microbial activity and composition of three different human donors and subsequently the epithelial permeability and immune response. Both inulin and AXOS decreased the pH during incubation (-1.5 pH units), leading to increased productions of acetate, propionate, and butyrate. Differences in terms of metabolites production could be linked to specific microbial alterations at genus level upon inulin/AXOS supplementation (i.e., Bifidobacterium, Bacteroides, Prevotella and unclassified Erysipelotrichaceae), as shown by 16S-targeted Illumina sequencing. Both products stimulated gut barrier and immune function with increases in TEER, NF-KB, IL-10, and IL-6. Ingredients with different structures selectively modulate the microbiota of a specific donor leading to differential changes at metabolic level. The extent of this effect is donor specific and is linked to a final specific modulation of the host's immune system.

Viscosity negatively affects the nutritional value of blue lupin seeds for broilers

This study examines the impact of Lupinus angustifolius variety (C) and inclusion level (L) in broiler diets on the nutritional value, viscosity of ileal digesta and activity of gut microbiota. The experiment was conducted on 154 female 21-day-old broilers, allocated to 11 groups (kept individually). A reference lupin-free diet and 10 test diets containing one of five lupin seeds; Kadryl, Regent, Dalbor, Bojar and Tango, mixed with the reference diet at a ratio of 25 : 75 or 32 : 68 dry matter (DM) (low or high level of inclusion) were prepared. Diets were fed for 6 days, excreta were collected over last 4 days. Apparent metabolizable energy corrected to zero N balance (AMEN) of diets and AMEN of lupin seeds were calculated. Birds were sacrificed, ileal and caecal digesta were pooled by segments from two birds, and the activity of bacterial enzymes was determined. The ileal digesta viscosity was measured immediately (ileal viscosity immediate (IVI)) or after 6 days storage at −18°C (ileal viscosity frozen). AMEN of test diets were lower than the reference diet. Lupin AMEN values ranged from 6.04 MJ/kg DM for Regent at high level to 9.25 MJ/kg DM for Bojar at low level. High inclusion level numerically decreased AMEN value in all cultivars, except for Kadryl, for which it increased (significant C×L interaction). The IVI value was 2.6 mPa·s in the reference group, but ranged from 6.3 to 21.7 mPa·s in lupin-fed birds. It increased significantly with level for Regent, Dalbor and Tango but not for the other two cultivars (significant C×L interaction). There was a negative correlation between IVI and: apparent total tract N retention, fat digestibility from test diets, AMEN of diets and lupins. Ileal viscosity immediate was positively correlated with the activity of ileal α- and β-glucosidase and negatively with ileal α-galactosidase and caecal α-glucosidase. Ileal viscosity frozen ranged from 3.2 to 5 mPa·s and it was not correlated with lupins AMEN. This suggests that the digesta viscosity caused by narrow-leafed lupin is detrimental to its nutritional value and interfere with the gut microbial activity. In addition, the lupins viscosity was measured by two in vitro methods: the water extract viscosity (WEV) method and after incubation in conditions imitating in vivo digestion (enzyme-treated extract viscosity (EEV)). In vivo viscosity was weakly reflected by in vitro measurements as there was no correlation between IVI and WEV or EEV. Overall, findings suggest that the different cultivars of narrow-leafed lupin may have different value for practical application in broiler diets.

A human pilot trial of ingestible electronic capsules capable of sensing different gases in the gut

Ingestible sensors are potentially a powerful tool for monitoring human health. Sensors have been developed that can, for example, provide pH and pressure readings or monitor medication, but capsules that can provide key information about the chemical composition of the gut are still not available. Here we report a human pilot trial of an ingestible electronic capsule that can sense oxygen, hydrogen, and carbon dioxide. The capsule uses a combination of thermal conductivity and semiconducting sensors, and their selectivity and sensitivity to different gases is controlled by adjusting the heating elements of the sensors. Gas profiles of the subjects were obtained while modulating gut microbial fermentative activities by altering their intake of dietary fibre. Ultrasound imaging confirmed that the oxygen-equivalent concentration profile could be used as an accurate marker for the location of the capsule. In a crossover study, variations of fibre intake were found to be associated with differing small intestinal and colonic transit times, and gut fermentation. Regional fermentation patterns could be defined via hydrogen gas profiles. Our gas capsule offers an accurate and safe tool for monitoring the effects of diet of individuals, and has the potential to be used as a diagnostic tool for the gut.

Gut Dysbiosis and Muscle Aging: Searching for Novel Targets against Sarcopenia.

Advanced age is characterized by several changes, one of which is the impairment of the homeostasis of intestinal microbiota. These alterations critically influence host health and have been associated with morbidity and mortality in older adults. “Inflammaging,” an age-related chronic inflammatory process, is a common trait of several conditions, including sarcopenia. Interestingly, imbalanced intestinal microbial community has been suggested to contribute to inflammaging. Changes in gut microbiota accompanying sarcopenia may be attenuated by supplementation with pre- and probiotics. Although muscle aging has been increasingly recognized as a biomarker of aging, the pathophysiology of sarcopenia is to date only partially appreciated. Due to its development in the context of the age-related inflammatory milieu, several studies favor the hypothesis of a tight connection between sarcopenia and inflammaging. However, conclusive evidence describing the signaling pathways involved has not yet been produced. Here, we review the current knowledge of the changes in intestinal microbiota that occur in advanced age with a special emphasis on findings supporting the idea of a modulation of muscle physiology through alterations in gut microbial composition and activity.

Dietary copper-fructose interactions alter gut microbial activity in male rats.

Dietary copper-fructose interactions contribute to the development of nonalcoholic fatty liver disease (NAFLD). Gut microbiota play critical roles in the pathogenesis of NAFLD. The aim of this study was to determine the effect of different dietary doses of copper and their interactions with high fructose on gut microbiome. Male weanling Sprague-Dawley rats were fed diets with adequate copper (6 ppm CuA), marginal copper (1.5 ppm CuM) (low copper), or supplemented copper (20 ppm CuS) (high copper) for 4 wk. Deionized water or deionized water containing 30% fructose (wt/vol) was given ad libitum. Copper status, liver enzymes, gut barrier function, and gut microbiome were evaluated. Both low- and high-copper diets led to liver injury in high-fructose-fed rats, and this was associated with gut barrier dysfunction, as shown by the markedly decreased tight junction proteins and increased gut permeability. 16S rDNA sequencing analysis revealed distinct alterations of the gut microbiome associated with dietary low- and high-copper/high-fructose feeding. The common features of the alterations of the gut microbiome were the increased abundance of Firmicutes and the depletion of Akkermansia. However, they differed mainly within the phylum Firmicutes. Our data demonstrated that a complex interplay among host, microbes, and dietary copper-fructose interaction regulates gut microbial metabolic activity, which may contribute to the development of liver injury and hepatic steatosis. The distinct alterations of gut microbial activity, which were associated with the different dietary doses of copper and fructose, imply that separate mechanism(s) may be involved. NEW & NOTEWORTHY First, dietary low- and high-copper/high-fructose-induced liver injury are associated with distinct alterations of gut microbiome. Second, dietary copper level plays a critical role in maintaining the gut barrier integrity, likely by acting on the intestinal tight junction proteins and the protective commensal bacteria Akkermansia. Third, the alterations of gut microbiome induced by dietary low and high copper with or without fructose differ mainly within the phylum Firmicutes.

EULAR 2017: Annual European Congress of Rheumatology, June 14–17, 2017, Madrid, Spain

EULAR 2017: Annual European Congress of Rheumatology, June 14–17, 2017, Madrid, Spain

Prebiotic Potential and Chemical Composition of Seven Culinary Spice Extracts.

The objective of this study was to investigate prebiotic potential, chemical composition, and antioxidant capacity of spice extracts. Seven culinary spices including black pepper, cayenne pepper, cinnamon, ginger, Mediterranean oregano, rosemary, and turmeric were extracted with boiling water. Major chemical constituents were characterized by RP‐HPLC‐DAD method and antioxidant capacity was determined by measuring colorimetrically the extent to scavenge ABTS radical cations. Effects of spice extracts on the viability of 88 anaerobic and facultative isolates from intestinal microbiota were determined by using Brucella agar plates containing serial dilutions of extracts. A total of 14 phenolic compounds, a piperine, cinnamic acid, and cinnamaldehyde were identified and quantitated. Spice extracts exhibited high antioxidant capacity that correlated with the total amount of major chemicals. All spice extracts, with the exception of turmeric, enhanced the growth of Bifidobacterium spp. and Lactobacillus spp. All spices exhibited inhibitory activity against selected Ruminococcus species. Cinnamon, oregano, and rosemary were active against selected Fusobacterium strains and cinnamon, rosemary, and turmeric were active against selected Clostridium spp. Some spices displayed prebiotic‐like activity by promoting the growth of beneficial bacteria and suppressing the growth of pathogenic bacteria, suggesting their potential role in the regulation of intestinal microbiota and the enhancement of gastrointestinal health. The identification and quantification of spice‐specific phytochemicals provided insight into the potential influence of these chemicals on the gut microbial communities and activities. Future research on the connections between spice‐induced changes in gut microbiota and host metabolism and disease preventive effect in animal models and humans is needed.

Gut Microbiota in Vascular Disease: Therapeutic Target?

Gut microbiota is increasingly recognized as a powerful regulator of host physiology. Most of its effects are mediated through metabolites acting as energy sources, signaling receptor ligands and substrates for host enzymes. Owing to the meta-stability and high amenability of the gut microbiota to modification by diet and environment predicting specific gut microbes or its metabolites responsible for different host metabolic states is often confounded. The Pubmed was searched for research articles on gut microbiota and cardiovascular disease. The searched articles reported a direct role of gut microbes in cardiovascular disorders (CVD). The interaction among gut microbial metabolism (through breakdown of certain dietary nutrients like choline), host immune system and lipid metabolism generate conditions that promote atherosclerosis development. Importantly, components of this interactive system can be explored to identify points of intervention in the path of disease development. Based on this strategies targeting gut microbial composition and activity are being explored as therapies against CVD. Use of archaebiotics and 3,3-dimethyl- 1-butanol aiming to reduce TMA (trimethylamine) conversion to TMAO (trimethylamine-N-oxide) and high fibre diets to reduce TMA precursors while simultaneously selecting for beneficial gut bacteria are attractive anti-atherogenic approaches. Success of these approaches in humans however, requires extensive research.

Dietary High and Low Copper‐Fructose Interactions Induce Hepatic Steatosis Associated with Distinct Alterations of Gut Microbial Activity in Male Rats

ObjectiveDietary copper‐fructose interactions play critical roles in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). The aim of this study was to determine the effect of different dietary doses of copper and their interactions with high fructose on gut microbial activity and the development of steatosis.MethodsMale weanling Sprague‐Dawley rats were fed diets with adequate copper (6 ppm, CuA), marginal copper (1.5 ppm, CuM) (low‐copper) or copper supplementation (20 ppm, CuS) (high‐copper) for 4 weeks. Deionized water or deionized water containing 30% fructose (w/v) was given ad lib. Copper status, liver enzymes, histology, gut barrier function and gut microbial activity were evaluated.ResultsCopper levels were significantly lower in rats fed with a marginal copper diet than in those fed with an adequate copper diet. However, high‐copper diet did not lead to excessive copper accumulation in the liver, likely due to the downregulation of copper transporter‐1(Ctr‐1) mRNA. Both low‐ and high‐copper diets led to liver injury and fat accumulation in high fructose fed rats, and this accumulation was associated with gut barrier dysfunction. The increased abundance of the gut Gram‐negative bacteria, Enterobacteriaceae, did not parallel plasma endotoxin levels, with low copper‐fructose induced steatosis being characterized with endotoxemia, whereas high copper‐fructose induced steatosis was not, despite the fact that both of these regimens resulted in increased gut permeability. Fecal metabolomics study and 16S rRNA gene expression analysis revealed distinct gut microbial metabolic characteristics in response to dietary low‐ and high‐copper high‐fructose feeding.ConclusionOur data demonstrated that dietary copper‐fructose interaction regulates gut microbial metabolic activity, which might contribute to the development of hepatic steatosis. The distinct alterations of gut microbial activity which were associated with the different dietary doses of copper and fructose imply that separate mechanism(s) may be involved.Support or Funding InformationThis study was supported in part by NIH Grants U01AA021901, U01AA022489, R01AA023681, an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM113226 and by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health under Award Number P50AA024337. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health (C.J.M.); K23AA018399, R01ES021375 (M.C.); the Veterans Administration (C.J.M.); and the U of L Clinical and Translational Pilot Program (C.J.M.).

One-year calorie restriction impacts gut microbial composition but not its metabolic performance in obese adolescents.

Recent evidence has disclosed a connection between gut microbial glycosidase activity and adiposity in obese. Here, we measured microbial α-glucosidase and β-galactosidase activities and sorted fluorescently labeled β-galactosidase containing (βGAL) microorganisms in faecal samples of eight lean andthirteen obese adolescents that followed a controlled calorie restriction program during one year. β-galactosidase is a highly distributed functional trait, mainly expressed by members of Blautia, Bacteroides, Alcaligenes, Acinetobacter and Propionibacterium. Only long-term calorie restriction induced clear changes in the microbiota of obese adolescents. Long-term calorie restriction induced significant shifts in total and βGAL gut microbiota, reducing the Firmicutes:Bacteroidetes ratio and enhancing the growth of beneficial microorganisms such as Bacteroides, Roseburia, Faecalibacterium and Clostridium XIVa. Moreover, the structure and composition of βGAL community in obese after long-term calorie restriction was highly similar to that of lean adolescents. However, despite this high compositional similarity, microbial metabolic performance was different, split in two metabolic states at a body mass index value of 25. Our study shows that calorie restriction is a strong environmental force reshaping gut microbiota though its metabolic performance is linked to host's adiposity, suggesting that functional redundancy and metabolic plasticity are fundamental properties of gut microbial ecosystem.