Search

Microalgae are a potential source of valuable products including drugs, chemicals, food supplements, biofuels, animal feed and fertilizers. In outdoor culture, biomass productivity is dependent on ...

A total of 105 yeast isolates was obtained from 15 sourdough samples collected from different regions in China and subjected to random amplified polymorphic DNA (RAPD) analysis. Six species were identified including Pichia membranifaciens, which has not previously been reported in Chinese sourdoughs. Different species of yeast were used in single-culture fermentation to make Chinese steamed bread (CSB). The volatiles of the CSB were captured by solid-phase microextraction method, separated and identified by gas chromatography-mass spectrometry. In total, 41 volatile compounds were found in all the steamed breads. All CSBs showed a similar volatile profile; however, significant differences in the quantity of some volatile compounds were seen among the CSB fermented by different yeast species. A partial least squares discriminant analysis showed that the CSBs could be separated by their characteristic volatile profiles. The study suggested that the aromatic properties of CSB are determined by the yeast used.

Few studies have focused on the capacity of lactic acid bacteria in utilizing soybean carbohydrates by genetic and phenotypic approaches. In the current study, genetic and phenotypic characteristics of soybean carbohydrate metabolism in Leuconostoc mesenteroides, Lactococcus lactis and Streptococcus thermophilus were investigated. The results indicated that all the 3 species have the potential capacity to utilize sucrose with a sucrose phosphoenolpyruvate-dependent phosphotransferase system (PTS) pathway mainly consisted of scrA, sacA, scrK and scrR. Among the 15 strains, only 1 L. lactis strain possessed both sucrose permease and PTS pathway. On the other hand, only Leu. mesenteroides among the 3 species have the genes related to α-galactosidases for potential capacity to metabolize raffinose-family oligosaccharides (RFO) in soybean. Four Leu. mesenteroides strains, DQHXN_Q03M16, FSDLZ60M2, DSCAB2M6 and DQHXN_Q38M5, possessed the complete α-galactosidases gene clusters of lacS-galA-galK-galT and high α-galactosidases activity, which contributed to the capacity of these strains to utilize RFO. These findings provide an approach to investigate the genetic and the phenotypic characteristics of Leu. mesenteroides, L. lactis and S. thermophilus in soybean carbohydrate metabolism for suitable strain selection in soybean fermentation.

Lactic acid bacteria (LAB) are widely used as probiotics in the food industry owing to their beneficial effects on human health. However, numerous antibiotic resistance genes have been found in LAB strains, especially tetracycline resistance genes. Notably, the potential transferability of these genes poses safety risks. To comprehensively evaluate tetracycline resistance in LAB, we determined the tetracycline susceptibility patterns of 478 LAB strains belonging to four genera and eight species. By comparing phenotypes with genotypes based on genome-wide annotations, five tetracycline resistance genes, tet(M), tet(W/N/W), tet(L), tet(S), and tet(45), were detected in LAB. Multiple LAB strains without tetracycline resistance genes were found to be resistant to tetracycline at the currently recommended cutoff values. Thus, based on the minimum inhibitory concentrations of tetracycline for these LAB strains, the species-specific microbiological cutoff values for Lactobacillus (para)gasseri, Lactobacillus johnsonii, and Lactobacillus crispatus to tetracycline were first developed using the Turnidge, Kronvall, and eyeball methods. The cutoff values for Lactiplantibacillus plantarum were re-established and could be used to better distinguish susceptible strains from strains with acquired resistance. Finally, we verified that these five genes play a role in tetracycline resistance and found that tet(M) and tet(W/N/W) are the most widely distributed tetracycline resistance genes in LAB.

Background: With an aging population, developing non-pharmacological interventions (NPIs) to delay dementia has become critical. Apart from cognitive decline, dementia is associated with multiple pathophysiology, including increased oxidative stress, dysregulated gene expressions, cytokine, neurotrophin, and stress markers, telomere shortening, and deteriorations in brain connectivity. Although mindfulness practices have been proposed to ameliorate these biological changes, no empirical studies were conducted. We thus aimed to investigate the effects of mindfulness awareness practice (MAP) to prevent cognitive decline and improve peripheral biomarkers in community-dwelling older adults diagnosed with mild cognitive impairment (MCI). Methods/Design: This was a single-blinded and parallel-group randomized controlled trial with two arms (intervention and active control arms), conducted over nine months. A total of 60 consenting community-dwelling older adults diagnosed with MCI were planned to be randomized in a 1:1 ratio to either the MAP or the Health Education Program (HEP). Interventions were performed weekly for the initial 12 weeks, and monthly for the subsequent six months. Outcome measures were assessed at baseline, 3-month, and 9-month post-intervention by blinded assessors. Primary outcomes were neurocognitive tests, comprehensive peripheral biomarkers, and brain imaging scans. Secondary outcomes included basic health screening measures, affective symptoms, and measures of physical functions. Linear-mixed models were used to examine the effects of MAP on these outcome measures. Significance: This is the first randomized controlled trial to systematically investigate the effects of a mindfulness intervention in improving cognitive functions and various biomarkers in community-dwelling older adults diagnosed with MCI. Our findings have the potential to inform mindfulness intervention as a novel approach to delay dementia.

The potential probiotic benefits of Bifidobacterium bifidum have received increasing attention recently. We used comparative genomic analysis to explore the differences in the genome and the physiological characteristics of B. bifidum isolated from the fecal samples of Chinese adults and infants. The relationships between genotypes and phenotypes were analyzed to assess the effects of isolation sources on the genetic variation of B. bifidum. The phylogenetic tree results indicated that the phylogeny of B. bifidum may be related to the geographical features of its isolation source. B. bifidum was found to have an open pan-genome and a conserved core genome. The genetic diversity of B. bifidum is mainly reflected in carbohydrate metabolism- and immune/competition-related factors, such as the glycoside hydrolase gene family, bacteriocin operons, antibiotic resistance genes, and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas. Additionally, the type III A CRISPR-Cas system was discovered in B. bifidum for the first time. B. bifidum strains exhibited niche-specific characteristics, and the results of this study provide an improved understanding of the genetics of this species.

Biofilms are aggregates of microorganisms that adhere to the surface of certain substances and produce extracellular polymers to improve their resistance to stress. However, only some Bifidobacterium strains can form biofilms on abiotic surfaces. The study evaluated the biofilm-forming abilities of six Bifidobacterium strains on grape seed flour (GSF) with a particle size of 80–120 μm. Bifidobacterium animalis, Bifidobacterium bifidum, and Bifidobacterium adolescentis formed weak biofilms, whereas Bifidobacterium pseudo, Bifibacterium breve, and Bifidobacterium longum formed strong biofilms on GSF. B. pseudo cells formed biofilm particles with a diameter of 2 mm, and their cell numbers reached 2.04 × 109 CFU/g at 32 h. There were almost no viable cells in the culture without GSF after 60 h; however, the number of biofilm cells on GSF was still over 106 CFU/g, indicating that biofilms improve cell survival. Field-emission scanning electron microscopy revealed the following stages in the bifidobacterial biofilm formation process: adsorption to GSF, secretion of extracellular substance, biofilm maturation and dispersal, and cell death. Collectively, these results strongly suggest that GSF is beneficial for Bifidobacterial biofilm growth, providing a theoretical basis for the production of highly resistant probiotics in the food industry.

The prevalence of atopic dermatitis (AD) has increased and a therapeutic strategy using probiotic intervention has been reported. The effects of different Bifidobacterium (B. breve, B. bifidum, B. animalis, B. infants, and B. adolescentis) on gut microbial changes were explored in 2,4-dinitrofluorobenzene (DNFB)-induced AD, a T helper type 2-dominant allergic disease. Oral administration of Bifidobacterium suppressed skin thickening and mast cell infiltration, blocked pro-inflammatory cytokines (IL-4, CCL11, IL-13, and CCL22), increased IL-10 and IFN-γ, and modulated the microbiome and ecology in the gut. Based on 16S rRNA results, DNFB treatment resulted in gut microbial dysbiosis, characterized by a decrease in the proportion of Firmicutes and an increase in Bacteroidetes. The core microbiome related to AD were also observed (Dorea, Prevotella, Sutterella, Odoribacter, and Pseudomonas). B. breve and B. bifidum treatments increased the relative abundance of Adlercreutzia, Streptococcus, Lactobacillus, Anaerostipes, and Anaerotruncus. The functional modules involved in fructose and mannose metabolism, propanoate metabolism, and fatty acid biosynthesis were upregulated, and these might be related to immune regulation and short-chain fatty acids (SCFA) production. Taken together, these results suggested that Bifidobacterium treatments affected gut microbial composition and structure, altered gut microbial ecosystem, and these alterations were closely associated with inflammation and SCFA production.

Genetic engineering of microalgae to accumulate high levels of medium-chain-length fatty acids (MCFAs) represents an attractive strategy to improve the quality of microalgae-based biodiesel, but it has thus far been least successful. We demonstrate that one limitation is the availability of fatty acyl-acyl carrier protein (ACP) substrate pool for acyl-ACP thioesterase (TE). A combinational expression platform that involved plant lauric acid-biased TE (C12TE) and MCFA-specific ketoacyl-ACP synthase (KASIV) increased lauric acid (C12:0) and myristic acid (C14:0) accumulation by almost sevenfold and fourfold, respectively, compared with native strain. These findings suggest a platform for further investigation into the enlargement of MCFA acyl-ACP substrate pool as an approach to sustainably improve quality of microalgae-based biodiesel with regard to MCFA production.

Probiotics administration can improve host health. This study aims to determine the effects of probiotics (Lactobacillus casei Zhang and Lactobacillus plantarum P-8) administration on milk production, milk functional components, milk composition, and fecal microbiota of dairy cows. Variations in the fecal bacteria microbiota between treatments were assessed based on 16S rRNA profiles determined by PacBio single molecule real-time sequencing technology. The probiotics supplementation significantly increased the milk production and the contents of milk immunoglobulin G (IgG), lactoferrin (LTF), lysozyme (LYS) and lactoperoxidase (LP), while the somatic cell counts (SCC) significantly decreased (P 0.05). Although the probiotics supplementation did not change the fecal bacteria richness and diversity, significantly more rumen fermentative bacteria (Bacteroides, Roseburia, Ruminococcus, Clostridium, Coprococcus and Dorea) and beneficial bacteria (Faecalibacterium prausnitzii) were found in the probiotics treatment group. Meanwhile, some opportunistic pathogens e.g. Bacillus cereus, Cronobacter sakazakii and Alkaliphilus oremlandii, were suppressed. Additionally, we found some correlations between the milk production, milk components and fecal bacteria. To sum up, our study demonstrated the beneficial effects of probiotics application in improving the quality and quantity of cow milk production.

In the present study, high light and nitrogen starvation with glucose-fed to the culture was found efficient to induce astaxanthin accumulation in Chlorella zofingiensis . Therefore, a two-step cultivation strategy including high biomass yield fermentation and outdoor induction with an energy-free RFP was conducted. During the fermentation, the highest cell density of 98.4 g L −1 and astaxanthin yield of 73.3 mg L −1 were achieved, which were higher than those so far reported in C. zofingiensis . During the outdoor induction, astaxanthin content was further increased by 1.5-fold leading to the highest astaxanthin productivity of 5.26 mg L −1 day −1 under an optimal dilution of 5-fold. Our work thus provided an effective two-step cultivation strategy for production of astaxanthin by C. zofingiensis .

Background Accumulating evidence points to an association between gut microbial abnormalities and depression disorder. The microbiota-gut-brain axis is an emerging target for treating depression using nutritional strategies, considering the numerous limitations of current pharmacological approaches. Here we studied the effect and probable mechanisms of psychobiotic treatment on depression. Methods Chronically stressed C57BL/6J male mice were administered viable Bifidobacterium breve CCFM1025 for 5 weeks prior to behavioral testing. Brain neurological alterations, serum corticosterone, cytokines levels, fecal microbial composition, and short-chain fatty acid (SCFA) content were measured. In addition, the effect of SCFA on 5-hydroxytryptophan (5-HTP) biosynthesis was investigated in an in vitro model of enterochromaffin cells (RIN14B). Results CCFM1025 treatment significantly reduced depression- and anxiety-like behaviors. The hyperactive hypothalamic-pituitary-adrenal response, as well as inflammation, were also alleviated, possibly via regulating the expression of glucocorticoid receptors (Nr3c1). Moreover, CCFM1025 also down-regulated the pCREB-c-Fos pathway but increased the expression of brain-derived neurotrophic factor (BDNF). Meanwhile, chronic stress-induced gut microbial abnormalities were restored, accompanied by increased SCFA and 5-HTP levels. The intestinal 5-HTP biosynthesis positively correlated with fecal SCFA and Bifidobacterium breve levels. Conclusions In summary, Bifidobacterium breve CCFM1025 showed considerable antidepressant-like and microbiota-regulating effects, which opens avenues for novel therapeutic strategies towards treating depression., Graphical abstract Bifidobacterium breve CCFM1025 may exert an antidepressant-like effect via the following pathways: (1) Reshaping gut microbial composition and metagenomic function, and increasing the production of beneficial metabolites. (2) Attenuating the hyperfunction of the hypothalamic-pituitary-adrenal axis and inflammation. (3) Upregulating BDNF expression while downregulating c-Fos expression in the brain. All colored arrows indicate increases (upward green) or decreases (downward red) of the measures. Black lines and arrows connect the elements in the metabolic pathway.Image 1, Highlights • CCFM1025 reshapes the gut microbial composition under the chronic stress. • CCFM1025 attenuates HPA axis hyperfunction and inflammation. • CCFM1025 alters the BDNF and c-FOS expression in the brain. • Antidepressant-like effect of CCFM1025 correlates with gut 5-HTP and SCFA.

Increasing evidence points to the effect of the gut microbiota on central nervous system functions. Supplementation of certain microbial strains has been demonstrated to alleviate depressive behaviors and neurological abnormalities. This study took the approach to screen for an anti-depressive Bifidobacterium longum strain from fourteen candidates and systematically verified its effect in a chronic stress-induced depression mice model. B. longum subsp. infantis strain CCFM687 could significantly enhance the biosynthesis of 5-hydroxytryptamine (5-HTP) in vitro in RIN14B cells through up-regulation of the Tph1 gene expression. Administration of CCFM687 in mice significantly improved the scores in behavioral tests and increased the level of 5-HTP and serotonin (5-HT) in the prefrontal cortex (PFC) of the brain. The brain-derived neurotrophic factor (BDNF) in the PFC was also increased, possibly through the 5-HT1A-CREB-BDNF pathway. In addition, CCFM687 alleviated the hyperactivity of the hypothalamic–pituitary–adrenal (HPA) axis response and accordingly reversed the peripheral inflammation status. Moreover, the stress-induced structural and functional dysbiosis of the gut microbiome was improved by CCFM687, through increased alpha diversity and abundance of butyrate-producing bacteria, in conjunction with inhibition of pathogenic gene expression. In summary, these results indicate that supplementation of B. longum subsp. infantis strain CCFM687 may prevent the onset of depression from chronic stress, and RIN14B could serve as an efficient cell model for rapid screening of anti-depressive probiotics.

A main target in microbiome research is the understanding and ability to safely and effectively modulate the microbiome to improve health. Hereto, we discuss the role of vitamins in relation to the gut microbiome and present a rationale for the modulation of gut microbial communities via selected systemic and colon-targeted vitamin administration.

Emerging studies have reported gut microbial composition plays a key role in alleviating AD clinical symptoms during the probiotic intervention, but the correlation among clinical symptoms, immune responses and gut microbial alteration needs to be explored. Therefore, the objective was to investigate the correlation during Bifidobacterium adolescentis intervention in DNFB-induced AD mice. The mice were randomly divided into nine groups and fed B. adolescentis for 3 weeks. At the end of the experiment, clinical and immune indicators were assessed. Flow cytometry was performed to explore the effect of B. adolescentis on regulatory T cells in the spleen. V3–V4 region of the 16S ribosomal RNA (rRNA) gene was sequenced to evaluate changes in the gut microbiota. Bifidobacteria adolescentis treatments reduced ear and skin thickness and suppressed eosinophils and mast cells infiltration. Th1- and Th2-type responses were regulated and the Tregs population was promoted in the spleen by B. adolescentis treatments. Bifidobacteria adolescentis increased the relative abundance of Lactobacillus but decrease Dorea and Pediococcus. Propionic and butyric acids were increased but isovaleric acid was decreased by B. adolescentis treatment. Besides, the functional modules, such as fatty acid biosynthesis, antigen processing and presentation were upregulated by B. adolescentis Ad1 treatment compared to the DNFB group. Collectively, these results imply that B. adolescentis with the role of immunomodulation promotes Treg differentiation and suppresses Th2 responses, and increases the proportion of Lactobacillus that is positively correlated to increase in propionic acid production, and thus has the potential for AD amelioration.

Constipation, which seriously affects living quality of people, is a common gastrointestinal disease. The engagement of the intestinal flora in the development of symptoms of constipation has been frequently hypothesized. In this study, constipated mice induced by loperamide were used to investige the alleviation of constipation by Bifidobacteria. Bifidobacteria was sorted out according to their adhesive properties into two groups. One group combined multiple strains of Bifidobacterium with adhesion property (CMB1), the other combined multiple strains of Bifidobacterium without adhesion property (CMB2). It was found that CMB1 can alleviate constipation more efficiently by improving the water, propionate and butyrate content in feces, and overall gastrointestinal transit time. Meanwhile, from the perspective of fecal microbiota, CMB1 alleviated constipation mainly by increasing the relative abundances of genera (Bifidobacterium, Lactobacillus, and Prevotella) associated with rapid bowel movement. From the perspective of cecal microbiota, CMB1 alleviated constipation mainly by increasing the relative abundances of genera Lactobacillus, Bacteroides, unclassified S24-7, Dorea, Ruminococcus, Coprococcus, and Rikenella, and decreasing the relative abundances of genera Oscillospira, Odoribacter and Unclassified F16, which are associated with methane production and colonic transit. Overall, changes of microbiota in caecum by CMB1 reflect the stage of constipation in mice more comprehensively than that in feces.

Timely response to outbreak of water-borne diseases caused by bacteria requires efficient monitoring and rapid detection strategies. Herein, we report a rapid DNA-based on-site detection system for specific detection of Pseudomonas aeruginosa. To evaluate the test performance of our method against spiked water samples, parallel tests based on real-time PCR and standard culture methods were concurrently performed. Test sensitivities of between 96.7% and 92.3% were obtained, based on the calculation obtained from qPCR and culture test, respectively, with a corresponding level of specificity of 92.9% and 83.3%. Time-to-result is around 45 min, with a detection limit of 1 CFU/100 mL. Here, a fully-deployable detection method where bacteria of-interest can be detected rapidly with high accuracy was described. This test method can be modified to detect other bacteria of-interest and can also be used in different applications. The test results can be obtained on-site and can therefore be particularly useful in public facilities health surveillance, where regulators can quickly determine if a site is safe or if other emergency response measures are required.IMPORTANCEPseudomonas aeruginosa is a well-established water quality biomarker, known to be associated to humans’ health risks. To ascertain the presence of this pathogen, relevant stakeholders currently rely on standard quantitative ISO methods (APHA 9213E) which require 6 days from sampling to results. This window could potentially lead to waterborne outbreaks if the contaminated water features are not shut down for proper and urgent mitigation. This manuscript describes a method to detect this disease-causing microorganism in its viable forms under 1 hour, with a sensitivity of 1 CFU/100mL. Besides providing valuable information of the quality of water system, this direct monitoring of pathogens can reduce substantial time needed from sampling to reporting. This method can be established as a platform technology for other pathogenic microorganisms. On-going work to develop economic point-of-care prototypes could facilitate quick screening of targeted waterborne pathogens and results in better assessment of public health risk and quick in devising emergency response measures and other management strategies.

Recent studies have realized the link between gut microbiota and human health and diseases. The question of diet, environment or gene is the determining factor for dominant microbiota and microbiota profile has not been fully resolved, for these comparative studies have been performed on populations of different ethnicities and in short-term intervention studies. Here, the Southern Chinese populations are compared, specifically the children of Guangzhou City (China), Penang City (west coast Malaysia) and Kelantan City (east coast Malaysia). These Chinese people have similar ancestry thus it would allow us to delineate the effect of diet and ethnicity on gut microbiota composition. For comparison, the Penang and Kelantan Malay children were also included. The results revealed that differences in microbiota genera within an ethnicity in different cities was due to differences in food type. Sharing the similar diet but different ethnicity in a city or different cities and living environment showed similar gut microbiota. The major gut microbiota (more than 1% total Operational Taxonomy Units, OTUs) of the children population are largely determined by diet but not ethnicity, environment, and lifestyle. Elucidating the link between diet and microbiota would facilitate the development of strategies to improve human health at a younger age.

A correction has been published and is appended to both the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Foods containing probiotics are regulated through Food Safety and Standards Regulations, 2016. Advisory Committee on Novel Foods is chaired by Food Standards Australia New Zealand and representatives from Australian state and territory jurisdictions and the New Zealand Ministry for Primary Industries. The Australia New Zealand Food Standards Code applies to all food sold, manufactured, imported or handled for sale in Australia or New Zealand. Most of the probiotic functional food products have been approved to have the health claims “enhance immunity” and/or “regulate gastrointestinal tract flora,” among the 27 permitted health claims. Food Safety and Standards Authority of India started working on creating a framework for regulating the functional foods sector, commonly called as nutraceuticals, in 2013. The Food Safety Law states that the China Food and Drug Administration under the State Council, in accordance with this law and the responsibilities identified by the State Council, is responsible for supervision and administrations of food production and trading activities.

Previous research reported that fermented yak milk had a diverse microbial composition. For this study, raw yak milk, qula, and fermented yak milk samples were collected from the Aba Tibetan autonomous region of China. The genus and species microbial composition of these samples were analyzed by high-throughput sequencing of 16S rRNA and groEL gene amplicons, and the volatile profile of the samples was quantified by gas chromatography-mass spectrometry. The results indicated variation in abundance of microbiota at the genus level among the fermented yak milk samples, with Lactobacillus as the most abundant genus in the majority of samples, ranging from 41.6 to 98.3%. The volatile profile of the samples varied among those collected from different villages. Correlations between bacterial composition and volatile compounds of the samples were also observed. Lactobacillus displayed a significant correlation with volatile compounds such as benzaldehyde, 2,3-pentanedione, ethanol, and ethyl acetate, whereas the samples with relatively high abundance of Streptococcus and Lactococcus displayed relatively low contents of volatile compounds.

The heavy metal cadmium (Cd) is a contaminant widely distributed in the food chain. In the present study, 8-week oral administration of a probiotic strain, Lactobacillus plantarum CCFM8610, markedly decreased blood Cd levels in volunteers. Further animal study showed that three L. plantarum strains administered orally exhibited significantly different effects on the regulation of bile acid (BA) metabolism and Cd excretion in mice. Among the strains, L. plantarum CCFM8610 showed the most significant effects on enhancing hepatic BA synthesis, biliary glutathione output, and fecal BA excretion. Biliary Cd output and fecal Cd excretion were markedly increased after L. plantarum CCFM8610 administration, resulting in a marked reduction in tissue Cd levels. The regulation of BA homeostasis and Cd excretion was due to the suppression of the enterohepatic farnesoid X receptor-fibroblast growth factor 15 (FXR-FGF15) axis by L. plantarum CCFM8610 and could be abolished by treatment with the FXR agonist GW4064. The regulatory effects were also related to the gut microbiota, as antibiotic pretreatment reversed L. plantarum CCFM8610-induced effects in BA and Cd metabolism.

Previous research has identified phosphoenolpyruvate-dependent phosphotransferase system and tagatose-6-phosphate (T6P) pathway of lactose/galactose metabolism in Lacticaseibacillus casei groups, which led to no galactose accumulation in fermented milk produced by Lb. paracasei. However, Lb. paracasei preferred lactose to galactose when grown in a mixture of the two sugars, indicating possibility of carbon catabolite repression of galactose catabolism in the fermented milk. Therefore, galactose accumulation was still observed during co-culturing of Lb. paracasei with Streptococcus thermophilus in fermented milk. We demonstrated that the transcriptional regulator lacR acts as a transcriptional repressor of the T6P pathway genes (lacA, lacC and lacD) and lacT acts as a transcriptional activator for genes (lacE) encoding the lactose-transporting PTS in the mixed lactose/galactose CDM medium, indicating possible dual repressive effects of global or local regulation on the carbon catabolism of galactose in Lb. paracasei.

With increasing globalisation, various diets from around the world are readily available in global cities. This study aimed to verify if multiethnic dietary habits destabilised the gut microbiome in response to frequent changes, leading to readily colonisation of exogenous microbes. This may have health implications. We profiled Singapore young adults of different ethnicities for dietary habits, faecal type, gut microbiome and cytokine levels. Subjects were challenged with Lactobacillus casei, and corresponding changes in microbiome and cytokines were evaluated. Here, we found that the majority of young adults had normal stool types (73% Bristol Scale Types 3 and 4) and faecal microbiome categorised into three clusters, irrespective of race and gender. Cluster 1 was dominated by Bacteroides, Cluster 2 by Prevotella, while Cluster 3 showed a marginal increase in Blautia, Ruminococaceae and Ruminococcus, without a predominant microbiota. These youngsters in the three faecal microbiome clusters preferred Western high sugary beverages, Southeast Asian plant-rich diet and Asian/Western diets in rotation, respectively. Multiethnic dietary habits (Cluster 3) led to a gut microbiome without predominant microbiota yet demonstrated colonisation resistance to Lactobacillus. Although Bacteroides and Prevotella are reported to be health-promoting but also risk factors for some illnesses, Singapore-style dietary rotation habits may alleviate Bacteroides and Prevotella associated ill effects. Different immunological outcome was observed during consumption of the lactobacilli among the three microbiome clusters.

Summary Microalgal neutral lipids (mainly in the form of triacylglycerols (TAGs)), feasible substrates for biofuel, are typically accumulated during the stationary growth phase. To make microalgal biofuels economically competitive with fossil fuels, generating strains that trigger TAG accumulation from the exponential growth phase is a promising biological approach. The regulatory mechanisms to trigger TAG accumulation from the exponential growth phase (TAEP) are important to be uncovered for advancing economic feasibility. Through the inhibition of pyruvate dehydrogenase kinase by sodium dichloroacetate (DCA), acetyl-CoA level increased, resulting to TAEP in microalga Dunaliella tertiolecta. We further reported refilling of acetyl-CoA pool through branched-chain amino acid catabolism contributed to an overall six-fold TAEP with marginal compromise (4%) on growth in a TAG-rich D. tertiolecta mutant from targeted screening. Herein, a 3-step α loop integrated metabolic model is introduced to shed lights on the neutral lipid regulatory mechanism. This article provides novel approaches to compress lipid production phase, and heightens lipid productivity and photosynthetic carbon capture via enhancing acetyl-CoA level, which would optimize renewable microalgal biofuel to fulfill the demanding fuel market. This article is protected by copyright. All rights reserved.

This study evaluates the ability ofLactobacillus rhamnosusGG (LGG) to activate DC and neutrophils and modulate T cell activation and the impact of bacterial dose on these responses. Murine bone marrow derived DC or neutrophils were stimulated with LGG at ratios of 5 : 1, 10 : 1, and 100 : 1 (LGG : cells) and DC maturation (CD40, CD80, CD86, CD83, and MHC class II) and cytokine production (IL-10, TNF-α, and IL-12p70) were examined after 2 h and 18 h coculture and compared to the ability of BCG (the present immunotherapeutic agent for bladder cancer) to stimulate these cells. A 2 h exposure to 100 : 1 (high dose) or an 18 h exposure to 5 : 1 or 10 : 1 (low dose), LGG : cells, induced the highest production of IL-12 and upregulation of CD40, CD80, CD86, and MHC II on DC. In DCs stimulated with LGG activated neutrophils IL-12 production decreased with increasing dose. LGG induced 10-fold greater IL-12 production than BCG. T cell IFNγand IL-2 production was significantly greater when stimulated with DC activated with low dose LGG. In conclusion, DC or DC activated with neutrophils exposed to low dose LGG induced greater Th1 polarization in T cells and this could potentially exert stronger antitumor effects. Thus the dose of LGG used for immunotherapy could determine treatment efficacy.

Glycerol production is modulated in some halo-tolerant organisms in response to extracellular osmotic stress. Glycerol-3-phosphate dehydrogenase (GPDH) is a rate-limiting enzyme of glycerol synthesis in both yeast and the green microalgae Dunaliella. In yeast, a High-Osmolarity-Glycerol (HOG) pathway, which is a mitogen-activated protein kinase (MAPK) cascade, has been suggested to activate the expression of GPDH and thus the accumulation of glycerol under osmotic stress. In Dunaliella tertiolecta, however, the osmo-regulatory mechanisms for glycerol synthesis are not well understood. In this study, the homologues of MAPK and GPDH in D. tertiolecta were cloned using Rapid Amplification of cDNA Ends (RACE) to investigate the molecular basis of the osmo-regulatory mechanisms. The isolated cDNA sequences were named DtMAPK (GenBank: KJ930518) and DtGPDH (GenBank: KJ930370), respectively. It was found that after osmotic shock DtMAPK and DtGPDH expression increased within 0.5 h and 1 h, respectively. In additio...

Here, we elaborate on the natural origin and use of enzymes and cultures in sustainable food processing. We also illustrate how enzymatically treated or fermented food can contribute to solving challenges involving nutrition and health, such as aging, malnutrition, obesity, and allergy.

This study demonstrated the protective effects of noni fruit and its fermented juice with different fermentation times against the acute liver injury caused by alcohol. In vitro trials were conducted to assess the antioxidant activities of noni fruit and fermented juice, while protective effects were confirmed by in vivo trials using mice model. The results showed that fresh noni fruit had higher antioxidant capacities (1,1-diphenyl-2-picrylhydrazyl scavenging activity, hydroxyl-radical scavenging ability, and reducing power) than fermented noni juice. However, in vivo experiments demonstrated that fermented noni juice had a comprehensive preventive effect on acute alcohol-induced liver injury, based on the histopathological analysis and the measurements of markers of serum and liver. The markers include aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, high density lipoprotein cholesterol, low density lipoprotein cholesterol, total cholesterol, and triglyceride. This study provides positive insights into the potential role of noni fruit and fermented juice in combating challenges presented by alcohol consumption and highlights the potential of noni fruit as functional food.

Di-(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer, which can enter the body through a variety of ways and exerted multiple harmful effects, including liver toxicity, reproductive toxicity and even glucose metabolism disorder. Many studies have suggested that changes of gut microbiota are closely related to the occurrence of various diseases, but the effects of DEHP exposure on gut microbiota are still unclear. It was found in this study that the damage to different tissues by DEHP on two strains each from two different species of male rodents before puberty was dose and time of exposure dependent, and also depending on the strain and species of rodent. Sprague-Dawley (SD) rats showed highest sensitivity to DEHP exposure, with most severe organ damage, highest Th1 inflammatory response and most significant body weight gain. Correspondingly, the gut microbiota of SD rats showed most significant changes after DEHP exposure. Only SD rats, but not Wistar rats, BALB/c and C57BL/6J mice showed an increase in Firmicutes/Bacteroidetes ratio and Proteobacteria abundance in the fecal samples, which are known to associate with obesity and diabetes. This is consistent with the increasing body weight gain which was only found in SD rats. In addition, the decrease in the level of butyrate, increase in the abundance of potential pathogens and microbial genes linked to colorectal cancer, Parkinson's disease, and type 2 diabetes in the SD rats were associated with issue and functional damages and Th1 inflammatory response caused by DEHP exposure. We postulate that the differential effects of DEHP on gut microbiota may be an important cause of the differences in the toxicity on different strains and species of rodents to DEHP.

Constipation is a disorder that affects people of all ages. Previous study showed Bifidobacterium spp. altered the faecal concentrations of short-chain fatty acids (SCFAs) while relieving constipation. Therefore, we speculated SCFAs might relieve constipation. We evaluated constipation-related indicators, SCFA levels and the faecal microbiota of constipated mice that were fed acylated starches derived from specific SCFAs for 1 month. It confirmed application of acylated starches resolved the issue of SCFAs absorption in small intestine by measuring the concentration of different SCFA in various tissues. Acetylated starch relieved constipation by increasing acetic acid-producing bacteria that were correlated positively with the small intestinal transit rate and water content of faeces, while butylated starch relieved constipation by increasing butyric acid-producing bacteria that were correlated negatively with the time to the first black stool defecation. These results indicated acetic acid and butyric acid play different roles in relieving constipation.

Trillions of microbes have evolved with and continue to live on human beings. With the rapid advances in tools and technology in recent years, new knowledge and insight in cross-talk between the microbes and their hosts have gained. It is the aim of this work to critically review and summarize recent literature reports on the role of microbiota and mechanisms involved in the progress and development of major human diseases, which include obesity, hypertension, cardiovascular disease, diabetes, cancer, Inflammatory Bowel Disease (IBD), gout, depression and arthritis, as well as infant health and longevity. Keywords: Gut microbiota, Human health, Disease

Loss of traditional diets by food globalization may have adverse impact on the health of human being through the alteration of gut microbial ecosystem. To address this notion, we compared the gut microbiota of urban (n = 17) and rural (n = 28) school-aged children in Thailand in association with their dietary habits. Dietary records indicated that children living in urban Bangkok tended to consume modern high-fat diets, whereas children in rural Buriram tended to consume traditional vegetable-based diets. Sequencing of 16S rRNA genes amplified from stool samples showed that children in Bangkok have less Clostridiales and more Bacteroidales and Selenomonadales compared to children in Buriram and bacterial diversity is significantly less in Bangkok children than in Buriram children. In addition, fecal butyrate and propionate levels decreased in Bangkok children in association with changes in their gut microbial communities. Stool samples of these Thai children were classified into five metabolotypes (MTs) based on their metabolome profiles, each characterized by high concentrations of short and middle chain fatty acids (MT1, n = 17), amino acids (MT2, n = 7), arginine (MT3, n = 6), amino acids, and amines (MT5, n = 8), or an overall low level of metabolites (MT4, n = 4). MT1 and MT4 mainly consisted of samples from Buriram, and MT2 and MT3 mainly consisted of samples from Bangkok, whereas MT5 contained three samples from Bangkok and five from Buriram samples. According to the profiles of microbiota and diets, MT1 and MT2 are characteristic of children in Buriram and Bangkok, respectively. Predicted metagenomics indicated the underrepresentation in MT2 of eight genes involved in pathways of butyrate biosynthesis, notably including paths from glutamate as well as pyruvate. Taken together, this study shows the benefit of high-vegetable Thai traditional diets on gut microbiota and suggests that high-fat and less-vegetable urban dietary habits alter gut microbial communities in Thai children, which resulted in the reduction of colonic short chain fatty acid fermentation.

Pectin has been known to lower circulating cholesterol by interacting with bile acid (BA) metabolism. The current study was aimed to investigate intestinal BA transport at the molecular level in a pig model. Twelve young pigs (11.05 ± 0.11 kg) were randomly divided into 2 groups and fed corn-soybean meal diets with either 5% pectin or cornstarch for 72 d. In pigs fed with pectin, total cholesterol and low-density lipoprotein cholesterol (LDL-C) were lowered but high-density lipoprotein (HDL-C) was increased (P < 0.05). Serum triglycerides tended to be lower in the pectin-fed animals (P = 0.093), whereas no change was noted in serum total bile acid. Along the length of the intestine, the size and composition of BA pools vary. The ratio of primary, secondary, taurine-conjugated, and glycine-conjugated BAs in the ileal pool was about 46:15:9:30, whereas it was 28:61:1:11 in the cecum and 22:65:3:9 in the colon (P < 0.05). In the feces, lithocholic acid and ursodeoxycholic acid (UDCA) made up of over 97% of the total BA pool. Overall, the ileum had the greatest expression of farnesoid X receptor (FXR) and apical sodium-coupled bile acid transporter (ASBT) than the duodenum, jejunum, cecum, and colon (P < 0.05), whereas organic solute transporters α/β (OSTα/β) gene expression was peaked in the ileum and jejunum (P < 0.05). Expression multidrug resistance protein 2 (MRP2) gradually decreased towards the end of the intestine (P < 0.05). Greater expression of G protein-coupled bile acid receptor and multidrug resistance protein 3 (MRP3) was found in the cecum and colon (P < 0.05). In pigs fed with 5% pectin, only cecal UDCA (P = 0.097) and hyocholic acid (P = 0.088) showed a decreasing tendency. But FXR, ASBT, and MRP2 were upregulated in the ileum and FXR, OSTα/β, MRP2, and MRP3 in the cecum of PEC-fed pigs (P < 0.05). Liver enzymes involved in BA biosynthesis (CYP7A1, CYP27A1, bile acid-CoA synthase, and bile acid-CoA:amino acid N acyltransferase) were not affected by pectin consumption. In conclusion, the abundant distribution of BA transporters and the greater BA pool size suggests the ileum as the major site for intestinal BA reabsorption in pigs. In the ileum, pectin increased in-and-out BA transport on the apical membrane by increasing ASBT and MRP2, but it increased the overall BA transport in the cecum by increasing OSTα/β and MRP3.

Dajiang-meju have been used as major ingredients for the preparation of traditional spontaneously fermented soybean paste in Northeast China. In this work, we sequenced and analyzed the metagenome of 12 dajiang-meju samples. To complement the metagenome analysis, we analyzed the taxonomic and functional diversity of the microbiota by metaproteomics (LC-MS/MS). The analysis of metagenomic data revealed that the communities were primarily dominated by Enterobacter, Enterococcus, Leuconostoc, Lactobacillus, Citrobacter and Leclercia. Moreover, changes in the functional levels were monitored, and metaproteomic analysis revealed that most of the proteins were mainly expressed by members of Rhizopus, Penicillium and Geotrichum. The number of sequences allocated to fungi in the fermentation process decreased, whereas the number of sequences assigned to bacteria increased with time of fermentation. In addition, functional metagenomic profiling indicated that a series of sequences related to carbohydrates and amino acids metabolism were enriched. Additionally, enzymes associated with glycolysis metabolic pathways were presumed to contribute to the generation of flavor in dajiang-meju. Proteins from different dajiang-meju samples involved in global and overview maps, carbohydrate metabolism, nucleic acid metabolism and energy metabolism were differentially expressed. This information improves the understanding of microbial metabolic patterns with respect to the metaproteomes of dajiang-meju and provides a powerful tool for studying the fermentation process of soybean products.

Pigs are one of the most important economic livestock. Gut microbiota is not only critical to the health but also the production efficiency of pigs. Manipulating gut microbiota relies on the full view of gut microbiome and the understanding of drive forces shaping microbial communities. 16s rDNA sequencing was used to profile microbiota along the longitudinal and radical axes to obtain the topographical map of microbiome in different intestinal compartments in young pigs. Alpha and beta-diversities revealed distinct differences in microbial compositions between the distal ileum and cecum and colon, as well as between the lumen and mucosa. Firmicutes and Proteobacteria dominated in the ileum, constituting 95 and 80% of the luminal and mucosa-attached microbiome. Transitioning from the small intestine to the large intestine, luminal Bacteroidetes increased from 1.69 to 45.98% in the cecum and 40.09% in the colon, while mucosal Bacteroidetes raised from 9 to 35.36% and 27.96%. Concurrently, luminal Firmicutes and Proteobacteria and mucosal-attached Proteobacteria remarkably decreased. By co-occurrence network analyses, Prevotellaceae, Ruminococcaceae, Lachnospiraceae and Veillonellaceae were recognized as the central nodes of luminal microbial network, and Prevotellaceae and Enterobacteriaceae, Caulobacteraceae, Enterococcaceae, Xanthomonadaceae, Pseudomonadaceae were identified as mucosal central nodes. Co-abundance was uncovered among Prevotellaceae, Lachnospiraceae, and Veillonellaceae in the luminal and mucosal microbiome, while opportunistic pathogens from γ-Proteobacteria in the mucosa. Strong co-exclusion was shown between Enterobacteriaceae with Prevotellaceae-centered microbial groups in the lumen. Redundancy analysis found bile acids and short chain fatty acids explained 37.1 and 41% of variations in the luminal microbial composition, respectively. Primary bile acid, taurine- and glycine- conjugated bile acids were positively correlated with Lactobacillaceae, Enterobacteriaceae, Clostridiaceae_1, Peptostreptococcaceae, whereas secondary bile acids, acetate, propionate, butyrate, and valerate were positively correlated with Prevotellaceae, Acidaminococcaceae, Ruminococcaceae, Lachnospiraceae, Desulfovibronaceae, Veillonellaceae. Functional analyses demonstrated that Prevotella, Veillonellaceae, Lachnospiraceae, and Ruminococcaceae were positively correlated with gene functions related to amino acids, energy, cofactors and vitamins metabolism, which are indispensable for the hosts. These results suggested site specific colonization and co-occurrence of swine gut microbiome closely relate to the microenvironment in each niche. Interactions of core gut microbiome greatly contributed to metabolism and/or immunity in the swine intestine.

It is now established that probiotics are strain-dependent, to further advance the concept of probiotic in the maintenance of health and treatment of dysbiosis, the scope of personalized probiotics need to be defined. Currently, probiotic products are marketed worldwide, with the assumption that probiotics with demonstrated health effects work on all people, irrespective of the genetic (ethnicity), environment (geographical location), dietary habit and life style. The effectiveness of probiotics are determined by 1) interactions with prevailing gastrointestinal (GI) commensal microbes, in promoting the establishment of beneficial microbes and elimination of pathogens, 2) Interaction with the host, in achieving a desirable probiotic effect, 3) Interaction with diet, to survive, proliferate and colonize GI, albeit temporary, and in the production of beneficial bioactive metabolites, such as short-chain-fatty acids (e.g. butyric acid), bile acid derivatives and trimethylamines. The benefits acquired from a probiotic are personal, depending on the health status, dietary habit and prevailing GI microbiota. Personalized probiotics should be established to achieve precision administration of specific probiotic effects for targeted population. Globalization and urbanization of human activities have led to merging of dietary habit, thus effective probiotics should evolve in tandem. Ultimately the probiotics of choice should be directed at specific physiological stage, health condition and targeted diseases.

Bifidobacteria are anaerobes and are difficult to culture in conventional fermentation system. It was observed that Bacillus subtilis natto enhanced growth of Bifidobacterium animalis subsp. lactis v9 by about 3-fold in a whole soybean solid-state co-fermentation, in a non-anaerobic condition. For the purpose of understanding the metabolic interactions between Bif. animalis subsp. lactis v9 and Ba. subtilis natto, the transcriptome of Bif. animalis subsp. lactis v9 and Ba. subtilis natto was analyzed in single and mixed cultures using RNA-Seq. Compared with the single culture, 459 genes of Bif. animalis subsp. lactis v9 were up regulated and 21 were down regulated in the mixed culture with Ba. subtilis natto, with more than 2-fold difference. Predictive metagenomic analyses suggested that Ba. subtilis natto up regulated transport functions, complex carbohydrates and amino acid metabolism, DNA repair, oxydative stress-related functions, and cell growth of Bif. animalis subsp. lactis v9. In the mixed culture with Bif. animalis subsp. lactis v9, only 3 transcripts of Ba. subtilis natto were over-expressed and 3115 were under-expressed with more than 2-fold difference. The highest down-regulated genes were those involved in carbohydrate and amino acid metabolism. The data presented here demonstrated a parasitic-like interaction regulated at the transcription level, between Ba. subtilis natto and Bif. animalis subsp. lactis in the mixed culture. The over-expression of genes involved in substrate uptake and metabolism in Bif. animalis subsp. lactis in the mixed culture nevertheless, led to its higher cell concentration in the nutrient rich whole soybean medium.

The microalga Dunaliella tertiolecta synthesizes intracellular glycerol as an osmoticum to counteract external osmotic pressure in high saline environments. The species has recently been found to release and accumulate extracellular glycerol, making it a suitable candidate for sustainable industrial glycerol production if a sufficiently high product titre yield can be achieved. While macronutrients such as nitrogen and phosphorus are essential and well understood, this study seeks to understand the influence of the micronutrient profile on glycerol production. The effects of metallic elements calcium, magnesium, manganese, zinc, cobalt, copper, and iron, as well as boron, on glycerol production as well as cell growth were quantified. The relationship between cell density and glycerol productivity was also determined. Statistically, manganese recorded the highest improvement in glycerol production as well as cell growth. Further experiments showed that manganese availability was associated with higher superoxide dismutase formation, thus suggesting that glycerol production is negatively affected by oxidative stress and the manganese bound form of this enzyme is required in order to counteract reactive oxygen species in the cells. A minimum concentration of 8.25 × 10−5 g L−1 manganese was sufficient to overcome this problem and achieve 10 g L−1 extracellular glycerol, compared to 4 g L−1 without the addition of manganese. Unlike cell growth, extracellular glycerol production was found to be negatively affected by the amount of calcium present in the normal growth medium, most likely due to the lower cell permeability at high calcium concentrations. The inhibitory effects of iron also affected extracellular glycerol production more significantly than cell growth and several antagonistic interaction effects between various micronutrients were observed. This study indicates how the optimization of these small amounts of nutrients in a two-stage system can lead to a large enhancement in D. tertiolecta glycerol production and should be considered during the design of a large scale bioprocess for this alternative route to glycerol. Biotechnol. Bioeng. 2015;112: 2163–2171. © 2015 Wiley Periodicals, Inc.

We describe factors promoting the exploration of locally sourced probiotics, targeting local populations to balance human needs and market opportunities. This would be particularly beneficial for people in developing countries, who generally lack access to affordable probiotics and are often exposed to poor hygiene conditions, toxic compounds, malnutrition, and chronic enteric infections. © 2015 Elsevier Ltd.

Oleaginous microalgae have been emerging as the third-generation feedstocks for biofuel production. Genetic manipulation for improving triacylglycerol (TAG) accumulation represents a promising approach towards the economics of microalgal biofuels. Acetyl-CoA, the essential carbon precursor for de novo fatty acid biosynthesis, can be derived from pyruvate catalyzed by pyruvate dehydrogenase, which is negatively regulated by pyruvate dehydrogenase kinase (PDK). In the present study, we characterized a PDK gene (NsPDK) from Nannochloropsis salina. Subcellular localization assay assisted by green fluorescence protein (GFP) fusion indicated the localization of NsPDK in mitochondria of N. salina cells. NsPDK knockdown via RNA interference strategy attenuated NsPDK expression at the mRNA level and its enzymatic activity in vivo, leading to faster TAG accumulation without compromising cell growth under high light stress conditions. Interestingly, the TAG increase was accompanied by a decline in membrane polar lipids. NsPDK knockdown also altered fatty acid profile in N. salina. Furthermore, transcriptional analysis suggested that the carbon metabolic pathways might be influenced by NsPDK knockdown leading to diverted carbon flux towards TAG synthesis. Taken together, our results demonstrate the role of NsPDK in regulating TAG accumulation and provide valuable insights into future manipulation of oleaginous microalgae for improving biofuel production.

The human being is a complex entity, involving interaction between microbes and the human host. Evidence shows that the nutritional value of food is influenced in part by the structure and operations of an individual's gut microbial community, and food in turn shapes the individual's microbiome. A conference was held to promote understanding of the intestinal microbiome and its implications for health and disease, particularly among Asian populations.Papers describing 1) the intestinal ecosystem in Asian populations, 2) changes in intestinal microbiota through life and its effects, 3) the Asian gut microbiota in disease conditions, 4) indigenous probiotics to maintain a healthy gut microbiota, 5) probiotic regulation in an Asian country, and 6) the results of a panel discussion are included in this report.The gut microbial inhabitants of Asian people differ from those of Europe and North America. Geographic location, diet, and ethnic background influence intestinal microbial composition. Urbanization and economic development have brought changes in traditional Asian diets, which in turn affected the gut microbiome, contributing to a shift in the region's health burden from infectious diseases to non-communicable chronic diseases. Novel probiotic strains of Indonesian origin demonstrated significant enhancement of humoral immune response in human studies. Knowledge gaps and implications for research to further understand the Asian gut microbiome were discussed.

Genetic engineering of microalgae to accumulate high levels of medium-chain-length fatty acids (MCFAs) represents an attractive strategy to improve the quality of microalgae-based biodiesel, but it has thus far been least successful. We demonstrate that one limitation is the availability of fatty acyl-acyl carrier protein (ACP) substrate pool for acyl-ACP thioesterase (TE). A combinational expression platform that involved plant lauric acid-biased TE (C12TE) and MCFA-specific ketoacyl-ACP synthase (KASIV) increased lauric acid (C12:0) and myristic acid (C14:0) accumulation by almost sevenfold and fourfold, respectively, compared with native strain. These findings suggest a platform for further investigation into the enlargement of MCFA acyl-ACP substrate pool as an approach to sustainably improve quality of microalgae-based biodiesel with regard to MCFA production.

The gut microbiota possesses diverse metabolic activities but its contribution towards heterogeneous toxicological responses is poorly understood. Here, we elucidate the role of the liver-gut microbiota axis in underpinning the hepatotoxicity of tacrine. We employed an integrated strategy combining pharmacokinetics, toxicology, metabonomics, genomics and metagenomics to elucidate and validate the mechanism of tacrine-induced hepatotoxicity in Lister hooded rats. Pharmacokinetic studies in rats demonstrated 3.3-fold higher systemic exposure to tacrine in strong responders that experienced transaminitis, revealing enhanced enterohepatic recycling of deglucuronidated tacrine in this subgroup, not attributable to variation in hepatic disposition gene expression. Metabonomic studies implicated variation in gut microbial activities that mapped onto tacrine-induced transaminitis. Metagenomics delineated greater deglucuronidation capabilities in strong responders, based on differential gut microbial composition (e.g. Lactobacillus, Bacteroides and Enterobacteriaceae) and ∼9% higher β-glucuronidase gene abundance compared to non-responders. In the validation study, co-administration with oral β-glucuronidase derived from Escherichia coli and pre-treatment with vancomycin and imipenem significantly modulated the susceptibility to tacrine-induced transaminitis in vivo. Conclusion: Our study establishes the pertinent gut microbial influences in defining the hepatotoxicity of tacrine, providing crucial insights for personalized medicine initiatives. This article is protected by copyright. All rights reserved.

Background RNA-Seq technology has received a lot of attention in recent years for microalgal global transcriptomic profiling. It is widely used in transcriptome-wide analysis of gene expression., particularly for microalgal strains with potential as biofuel sources. However, insufficient genomic or transcriptomic information of non-model microalgae has limited the understanding of their regulatory mechanisms and hampered genetic manipulation to enhance biofuel production. As such, an optimal microalgal transcriptomic database construction is a subject of urgent investigation. Results Dunaliella tertiolecta, a non-model oleaginous microalgal species, was sequenced via Illumina MISEQ and HISEQ 4000 in RNA-Seq studies. The high quality high-throughout sequencing data were explored using high performance computing (HPC) in a petascale data center and subjected to de novo assembly and parallelized mpiBLASTX search with multiple species. As a result, a transcriptome database of 17,845 was constructed (~95% completeness). This enlarged database constructed fueled the RNA-Seq data analysis, which was validated by a nitrogen deprivation (ND) study that induces triacylglycerol (TAG) production. Conclusions The new paralleled assembly and annotation method under HPC presented here allows the solution of large-scale data processing problems in acceptable computation time. There is significant increase in the number of transcriptomic data achieved and observable heterogeneity in the performance to identify differentially expressed genes in the ND treatment paradigm. The results provide new insights as to how response to ND treatment in microalgae is regulated. ND analyses highlight the advantages of this database generated in this study that could also serve as a useful resource for future gene manipulation and transcriptome-wide analysis. We thus demonstrate the usefulness of exploring the transcriptome as an informative platform for functional studies and genetic manipulations in similar species. Electronic supplementary material The online version of this article (doi:10.1186/s12859-017-1551-x) contains supplementary material, which is available to authorized users.