Induced Gut Microbiota Dysbiosis Research Articles

Gut microbiota-derived inosine from dietary barley leaf supplementation attenuates colitis through PPAR\u03b3 signaling activation

BackgroundUlcerative colitis is a type of chronic inflammatory bowel disease closely associated with gut microbiota dysbiosis and intestinal homeostasis dysregulation. Barley leaf (BL) has a long history of use in Traditional Chinese Medicine with potential health-promoting effects on intestinal functions. However, its mechanism of action is not yet clear. Here, we explore the potential modulating roles of gut microbial metabolites of BL to protect against colitis and elucidate the underlying molecular mechanisms.ResultsUsing 16S rRNA gene-based microbiota analysis, we first found that dietary supplementation of BL ameliorated dextran sulfate sodium (DSS)-induced gut microbiota dysbiosis. The mechanisms by which BL protected against DSS-induced colitis were resulted from improved intestinal mucosal barrier functions via the activation of peroxisome proliferator-activated receptor (PPAR)γ signaling. In addition, metabolomic profiling analysis showed that the gut microbiota modulated BL-induced metabolic reprograming in the colonic tissues particularly by the enhancement of glycolysis process. Notably, dietary BL supplementation resulted in the enrichment of microbiota-derived purine metabolite inosine, which could activate PPARγ signaling in human colon epithelial cells. Furthermore, exogenous treatment of inosine reproduced similar protective effects as BL to protect against DSS-induced colitis through improving adenosine 2A receptor (A2AR)/PPARγ-dependent mucosal barrier functions.ConclusionsOverall, our findings suggest that the gut microbiota-inosine-A2AR/PPARγ axis plays an important role in the maintenance of intestinal homeostasis, which may represent a novel approach for colitis prevention via manipulation of the gut microbial purine metabolite.7KxheC7u6V5hPgskc1_WuPVideo

Impact of gut microbiota on plasma oxylipins profile under healthy and obesogenic conditions

Oxylipins (OXLs) are bioactive lipid metabolites derived from polyunsaturated fatty acids (PUFAs) which act as signaling molecules and are involved in inflammatory processes such as those that occur in obesity. On the other hand, gut microbiota plays an essential role in regulating inflammatory responses. However, little is known about the potential impact of gut bacteria on OXLs metabolism. Thus, the objective of this study was to investigate the effect of gut microbiota dysbiosis on plasma oxylipins profile in healthy and diet-induced obese animals. Eight-week-old male Wistar rats were fed with either a standard or cafeteria diet (CAF) for 5 weeks and administered an antibiotic cocktail (ABX) in the drinking water (Ampicillin: 1g/ml, Vancomycin: 0.5g/ml, Imipenem: 0.25g/ml) for the last 2 weeks in order to induce gut microbiota dysbiosis. Metabolomics analysis of OXLs in plasma was performed by HPLC-MS analysis. No antibiotic treated animals were included as controls. Plasma OXLs profile was significantly altered due to both CAF feeding and ABX administration. ABX effect was more pronounced under obesogenic conditions. Several significant correlations between different bacteria taxa and these lipid mediators were observed. Among these, the positive correlation of Proteobacteria with LTB4, a proinflammatory OXL involved in obesity-related disorders, was especially remarkable. Gut microbiota plays a key role in regulating these lipid metabolites and, therefore, affecting oxylipins-mediated inflammatory processes. These results are the first evidence to our knowledge of gut microbiota impact on OXLs metabolism. Moreover, this can set the basis for developing new obesity markers based on OXLs and gut microbiota profiles.

Cigarette smoking exposure breaks the homeostasis of cholesterol and bile acid metabolism and induces gut microbiota dysbiosis in mice with different diets

Exposure of humans to second-hand smoking (SHS) increases glucose and lipid metabolic disorders. The link of hepatic metabolic dysfunction to environmental cigarette smoking has been noticed, but the related mechanism is still unclear. C57BL/6 mice with normal food diet (NFD) or high fat diet (HFD) were exposed to 15 min cigarette smoking twice a day in a 0.038 m3 box for 4 weeks, and the concentration of nicotine in the air of the box was 21.05 mg/m3 during the smoke exposure. Liver tissues and serum were collected for gene expression and biochemistry test. The fecal microbiota was also checked through 16S rDNA sequences. Cigarette smoking exposure increased the accumulation of total cholesterol (TC) in liver, and the expression of cholesterol synthesis-related genes was upregulated. The expression of CYP8B1 protein was significantly down-regulated, and the ratio of cholic acid (CA) to chenodeoxycholic acid (CDCA) was significantly reduced in the liver of mice exposed to cigarette smoking especially for HFD group. Cigarette smoking exposure caused insulin resistance in the liver of mice with HFD. The composition of the gut microbiota was altered with the exposure of cigarette smoking, and the change of the distribution of primary bile acids might be one of the reasons. It was concluded that cigarette smoking would break the homeostasis of cholesterol and bile acids metabolism and changed the composition of gut microbiota. Our discoveries confirmed that smoking bans are important for the public health.

Low concentrations of imidacloprid exposure induced gut toxicity in adult zebrafish (Danio rerio)

Neonicotinoid insecticide imidacloprid (IMI) is widely used in agriculture, and its repeated application may result in environmental pollution. Recently, the toxicity of IMI to non-target animals has received increasing attention. In the current study, adult zebrafish were exposed to low concentrations of IMI (100 and 1000 μg/L) for 21 days. The results showed that IMI exposure induced intestinal histological injury and oxidative stress in the gut of zebrafish, and the levels of superoxide dismutase (SOD), catalase (CAT) were noticeably increased. Furthermore, IMI exposure also resulted in higher intestinal LPS levels and significant increases in the expression of inflammatory factors. Simultaneously, IMI exposure also slightly induced gut microbiota dysbiosis and specific bacteria alterations. These findings indicated that low concentrations of IMI could induce gut toxicity in adult zebrafish, which could provide new insights into the potential risks of IMI to aquatic animals.

Dietary betaine prevents obesity through gut microbiota-drived microRNA-378a family

ABSTRACT Betaine is a natural compound present in commonly consumed foods and may have a potential role in the regulation of glucose and lipids metabolism. However, the underlying molecular mechanism of its action remains largely unknown. Here, we show that supplementation with betaine contributes to improved high-fat diet (HFD)-induced gut microbiota dysbiosis and increases anti-obesity strains such as Akkermansia muciniphila, Lactobacillus, and Bifidobacterium. In mice lacking gut microbiota, the functional role of betaine in preventing HFD-induced obesity, metabolic syndrome, and inactivation of brown adipose tissues are significantly reduced. Akkermansia muciniphila is an important regulator of betaine in improving microbiome ecology and increasing strains that produce short-chain fatty acids (SCFAs). Increasing two main members of SCFAs including acetate and butyrate can significantly regulate the levels of DNA methylation at host miR-378a promoter, thus preventing the development of obesity and glucose intolerance. However, these beneficial effects are partially abolished by Yin yang (YY1), a common target gene of the miR-378a family. Taken together, our findings demonstrate that betaine can improve obesity and associated MS via the gut microbiota-derived miR-378a/YY1 regulatory axis, and reveal a novel mechanism by which gut microbiota improve host health.

The effects of high-density polyethylene and polypropylene microplastics on the soil and earthworm Metaphire guillelmi gut microbiota

As an emerging pollutant in terrestrial ecosystem, studies on the effects of microplastics on the gut microbiota of terrestrial organisms are relatively little even though gut microbiota is closely related to host health, metabolism and immunity as well as soil decomposition processes. In this study, earthworms Metaphire guillelmi were exposed to soil amended with 0.25% (w/w) high-density polyethylene (HDPE, 25 μm) or polypropylene (PP, 13 μm) microplastics for 28 d. The ingestion of HDPE and PP microplastics by M. guillelmi was clearly demonstrated by Nile Red fluorescence staining method. There were significant differences for the microbiota between the M. guillelmi gut and the surrounding soil, which may result from the influence of specific conditions in the gut habitat. HDPE and PP microplastics exposure did not induce gut microbiota dysbiosis in M. guillelmi. However, PP microplastics exposure significantly reduced bacterial diversity and altered bacterial community structure in the soil. Specifically, the relative abundance of Aeromonadaceae and Pseudomonadaceae significantly increased while the relative abundance of Nitrososphaeraceae and two unidentified families affiliated with Proteobacteria significantly decreased. This study broadens our understanding of the ecotoxicity of microplastics on the soil and gut microbiota of terrestrial organisms.

Long-term exposure to phenanthrene at environmental-level induces intestinal dysbiosis and disrupted hepatic lipid metabolism in mice.

Phenanthrene (Phe), among the most ubiquitous polycyclic aromatic hydrocarbons (PAHs) existing in nature and foodstuffs, has severe effects on hepatic lipids metabolism. However, the detailed mechanism involved is still unknown. For environmental chemicals can disturb intestinal microbiota, which plays a vital role in lipids metabolism, we hypothesized that oral exposure to Phe may disrupt the intestinal microbiota, leading to the induction of an abnormal inflammatory response and lipid metabolism dysfunction. Herein, male mice were orally exposed to Phe (0.05, 0.5 and 5mg/kg/2d) for ten weeks and the results showed that long term exposure to Phe induced significant alteration in relative Bacteroidetes, Firmicutes and Proteobacteria abundance in male mice. Histopathological anomalies, and significantly increased hepatic levels of free fatty acid, cholesterol and triglyceride were observed as well. The expression of hepatic proteins linked to lipid metabolism including peroxisome proliferator-activated receptors (PPARs), liver X receptor β (LXRβ) and retinoid X receptors (RXRs) were upregulated. The importance of the gut microbiota in Phe-altered lipid metabolism disorder was further confirmed by fecal microbiota transplantation (FMT). FMT intervention boosted microbial diversity and attenuated Phe-induced elevation in liver somatic index and hepatic total lipids levels. These results demonstrated that environmental-level Phe altered the composition of gastrointestinal bacteria and subsequently induced hepatic lipid metabolism disorder. These results would be helpful for understanding the health risk posed by Phe.

Simulated microgravity suppresses MAPK pathway-mediated innate immune response to bacterial infection and induces gut microbiota dysbiosis.

During spaceflight, astronauts are subjected to various physical stressors including microgravity, which could cause immune dysfunction and thus potentially predispose astronauts to infections and illness. However, the mechanisms by which microgravity affects innate immunity remain largely unclear. In this study, we conducted RNA-sequencing analysis to show that simulated microgravity (SMG) suppresses the production of inflammatory cytokines including tumor necrosis factor (TNF) and interleukin-6 (IL-6) as well as the activation of the innate immune signaling pathways including the p38 mitogen-activated protein kinase (MAPK) and the Erk1/2 MAPK pathways in the Enteropathogenic escherichia coli (EPEC)-infected macrophage cells. We then adopted hindlimb-unloading (HU) mice, a model mimicking the microgravity of a spaceflight environment, to demonstrate that microgravity suppresses proinflammatory cytokine-mediated intestinal immunity to Citrobacter rodentium infection and induces the disturbance of gut microbiota, both of which phenotypes could be largely corrected by the introduction of VSL#3, a high-concentration probiotic preparation of eight live freeze-dried bacterial species. Taken together, our study provides new insights into microgravity-mediated innate immune suppression and intestinal microbiota disturbance, and suggests that probiotic VSL#3 has great potential as a dietary supplement in protecting individuals from spaceflight mission-associated infections and gut microbiota dysbiosis.

Lycium barbarum relieves gut microbiota dysbiosis and improves colonic barrier function in mice following antibiotic perturbation

• Antibiotics decrease the microbial diversity and induce gut microbiota dysbiosis. • Lycium barbarum (LB) alters the gut microbiota and increases short chain fatty acids. • LB treatment can relieve the gut microbiota dysbiosis after antibiotic perturbation. • LB improves colonic barrier function by altering the gut microbiota composition. Diet and antibiotic strongly affect human health by modulating gut microbiota (GM) composition. To investigate how Lycium barbarum (LB) relieves GM dysbiosis and enhances colonic barrier function, C57BL/6 mice were chronically exposed to sub-therapeutic antibiotic dosages or not (control), and fed a 1.5% LB diet for 10 weeks. HiSeq sequencing of 16S rDNA revealed that oral antibiotics distinctly lowered the microbial diversity and richness, Bacteroidetes, Firmicutes, Bacteroidales_S24-7_group, Lachnospiraceae, Ruminococcaceae, Lachnospiraceae_NK4A136_group , Lachnoclostridium , Akkermansia , Anaerotruncus , and Odoribacter , as well as increased Proteobacteria, Enterobacteriaceae, Enterococcaceae, Escherichia-Shigella , Morganella , and Enterococcus . Compared with the antibiotic-treated group, dietary LB reversed the variations in these bacteria, improved the abundance of certain short-chain fatty acid (SCFA)-producing bacteria, SCFA concentrations, and decreased fecal ammonia and pH value. Accordingly, this promoted the expression of tight junction proteins, immune barrier, sequentially improved barrier function, histomorphology, and development in the intestine. The results show that dietary LB can partially mitigate antibiotics-induced dysbiosis.

Bisphenol A exposure induces gut microbiota dysbiosis and consequent activation of gut-liver axis leading to hepatic steatosis in CD-1 mice

Interactions between the intestine and the liver, the so-called ‘gut-liver axis’, play a crucial role in the onset of hepatic steatosis and non-alcoholic fatty liver disease. However, not much is known about the impact of environmental pollutants on the gut-liver axis and consequent hepatic steatosis. Bisphenol A (BPA), a widely used plasticiser, is an important environmental contaminant that affects gut microbiota. We hypothesised that BPA induces hepatic steatosis by promoting gut microbiota dysbiosis and activating the gut-liver axis. In this study, male CD-1 mice were fed with diet containing BPA (50 μg/kg body weight/day) for 24 weeks. Dietary exposure to BPA increased lipid contents and fat accumulation in the liver. Analysis of 16 S rRNA gene sequencing revealed that the diversity of gut microbiota reduced and the composition of gut microbiota was altered in the BPA-fed mice. Further, the abundance of Proteobacteria, a marker of dysbacteria, increased, whereas the abundance of Akkermansia, a gut microbe associated with increased gut barrier function and reduced inflammation, markedly decreased. Expression levels of intestinal tight junction proteins (zona occludens-1 and occludin) also decreased drastically, leading to increased intestinal permeability and elevated levels of endotoxins. Furthermore, BPA up-regulated the expression of Toll-like receptor 4 (TLR4) and phosphorylation of nuclear factor-kappa B (NF-κB) in the liver and increased the production of inflammatory cytokines, including interleukin-1β, interleukin-18, tumour necrosis factor-α, and interleukin-6. Take together, our work indicated that dietary intake of BPA induced hepatic steatosis, and this was closely related to dysbiosis of gut microbiota, elevated endotoxin levels, and increased liver inflammation through the TLR4/NF-κB pathway.

Low-concentration of dichloroacetonitrile (DCAN) in drinking water perturbs the health-associated gut microbiome and metabolic profile in rats

Dichloroacetonitrile (DCAN) is one of the emerging nitrogenous disinfection by-products (DBPs) in drinking water. However, its potential toxicological effects remain poorly understood, especially at a low concentration found in the environment. In the present study, we investigated whether the consumption of low-concentration DCAN through drinking water would produce significant effects in male SD rats, with particular focus on their physiological traits and changes in their gut microbiome and metabolite profiles. After a 4-weeks DCAN intervention, significant changes were observed in the body weight, blood indices, and histology in DCAN-treated (100 μg/L) group. Proteobacteria was relatively less abundant in 20 and 100 μg/L DCAN-treated groups compared with that in the control group at phylum level. At genus level, Parasutterella and Anaerotruncus were significantly less abundant in both 20 and 100 μg/L DCAN-treated groups than that in the control group. Furthermore, the gut microbiota-related metabolites were dramatically perturbed after DCAN consumption. In the 20 and 100 μg/L DCAN-treated groups, there were 48 and 95 altered metabolites, respectively, and were found to be involved in sphingolipid signaling pathway, fatty acid biosynthesis, and cGMP−PKG signaling pathway. In summary, we demonstrated that consumption of low-concentration DCAN through drinking water could impair host health and induce gut microbiota dysbiosis and gut microflora-related metabolic disorders in male SD rats. Our findings highlight the potential toxicity of low-concentration DBPs and provide new insight into potential causal relationship between low concentration DBPs found in the drinking water and the host health.

Allicin Modifies the Composition and Function of the Gut Microbiota in Alcoholic Hepatic Steatosis Mice.

The intestinal microbiome plays an important role in the pathogenesis of liver diseases. Alcohol intake induces gut microbiota dysbiosis and alters its function. This study investigated the antibiotic effect of allicin in mice with hepatic steatosis. Male C57BL/6 mice were administered an ethanol diet supplemented with allicin (5 and 20 mg/(kg bw day)) for 4 weeks. Allicin modified the gut microbiota composition. Cecal microbiota exhibited a positive correlation with alcohol and hepatic triacylglycerol, but were suppressed with allicin. Ethanol diet with 5 mg of allicin induced a lower intestinal permeability compared to the ethanol diet alone. Allicin mediated the lipopolysaccharide (LPS)-CD14-toll-like receptor 4 (TLR4)-induced hepatic inflammation pathway by reducing LPS, CD14, TLR4, and pro-inflammatory cytokines-tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. However, hepatic inflammation primarily resulted from alcohol toxicity rather than LPS production in the gut. The prediction of functional profiles from metagenomic 16S ribosomal RNA (rRNA) data revealed different functional profiles in each group. The predicted aldehyde dehydrogenase tended to increase in alcoholic mice administered allicin. The predicted LPS-related pathway and LPS biosynthesis protein results exhibited a similar trend as plasma LPS levels. Thus, alcohol and allicin intake shapes the gut microbiota and its functional profile and improves the CD14-TLR4 pathway to alleviate inflammation in the liver.

Long-Term Effects of Multi-Drug-Resistant Tuberculosis Treatment on Gut Microbiota and Its Health Consequences.

Gut microbiota dysbiosis has adverse health effects on human body. Multi-drug-resistant tuberculosis (MDR-TB) treatment uses a variety of antibiotics typically for more than 20 months, which may induce gut microbiota dysbiosis. The aim of this study is to investigate the long-term effects of MDR-TB treatment on human gut microbiota and its related health consequences. A total of 76 participants were recruited at a hospital in Linyi, China. The study included one active MDR-TB treatment group, one recovered group from MDR-TB and two treatment-naive tuberculosis groups as control. The two treatment-naïve tuberculosis groups were constructed to match the sex and the age of the active MDR-TB treatment and the recovered group, respectively. The fecal and blood samples were collected and analyzed for gut microbiota and metabolic parameters. An altered gut microbiota community and a loss of richness were observed during the MDR-TB treatment. Strikingly, 3–8 years after recovery and discontinuing the treatment, the gut microbiota still exhibited an altered taxonomic composition (p = 0.001) and a 16% decrease in richness (p = 0.018) compared to the gut microbiota before the treatment. The abundance of fifty-eight bacterial genera was significantly changed in the MDR-TB recovered group versus the untreated control group. Although there were persistent and pervasive gut microbiota alterations, no gastrointestinal symptom such as abdominal pain, diarrhea, nausea, flatulence, and constipation was observed in the recovered group. However, chronic disorders may be indicated by the elevated level of low-density lipoprotein cholesterol (LDLC) (p = 0.034) and total cholesterol (TC) (p = 0.017). These adverse lipid changes were associated with the altered gut bacterial taxa, including phylum Firmicutes and Verrucomicrobia and genera Adlercreutzia, Akkermansia, Butyricicoccus, Coprococcus, Clostridioides, Eubacterium, Erysipelatoclostridium, Fusicatenibacter, Klebsiella, Psychrobacter, and Streptococcus. Collectively, MDR-TB treatment induced a lasting gut microbiota dysbiosis, which was associated with unfavorable changes in lipid profile.

The emerging PFOS alternative OBS exposure induced gut microbiota dysbiosis and hepatic metabolism disorder in adult zebrafish

Sodium ρ-perfluorous nonenoxybenzene sulfonate (OBS), as a novel the alternatives of PFASs, is widely used in many fields of life. Here, adult male zebrafish selected were exposed to OBS at concentrations of 3, 30 and 300 μg/L for 7 and 21 days, respectively. Based on the gut microbiota analysis, at genus level, the relative abundance of the Flavobacterium, Hyphomicrobium, Paracoccus, Lawsonia, Plesiomonas and Vibrio changed significantly in the gut of zebrafish after exposure to 300 μg/L OBS. In addition, the liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis suggested that a total of 1077 metabolites in pos-model and a total of 706 metabolites in neg-model changed significantly from the liver, and these changed metabolites were tightly related to several pathways including amino acid, pyrimidine and purine metabolism, etc. Furthermore, the changed gut bacteria including Flavobacterium, Hyphomicrobium, Paracoccus, Lawsonia, Plesiomonas and Vibrio at genus level were significantly correlated with various metabolites (succinic acid, leucine, xanthine, orotic acid, nicotinic acid, etc.). Taken together, all the results showed that low dose of OBS exposure could induce the dysbiosis of gut microbiota and disturbed the hepatic metabolism balance in adult male zebrafish.

Dietary Supplementation With Citrus Extract Altered the Intestinal Microbiota and Microbial Metabolite Profiles and Enhanced the Mucosal Immune Homeostasis in Yellow-Feathered Broilers.

The present study aimed to investigate the effects of citrus extract (CE) on intestinal microbiota, microbial metabolite profiles, and the mucosal immune status in broilers. A total of 540 one-day-old yellow-feathered broilers were randomly allotted into three groups and fed a basal diet (control group), or a basal diet containing 10 mg/kg of zinc bacitracin (antibiotic group), or 10 mg/kg of CE (CE group). Each treatment consisted of six replicates, with 30 broilers per replicate. After 63-day feeding, two broilers per replicate were randomly selected and slaughtered, and their ileal and cecal digesta and ileal tissue were collected for microbial composition, microbial metabolites, and gene expression analysis. The results showed that CE significantly increased the abundance of Barnesiella and Blautia than did the antibiotic group (adjusted P < 0.05), whereas it decreased the abundance of Alistipes and Bacteroides (adjusted P < 0.05). Meanwhile, the CE group also increased the numbers of Bifidobacterium and Lactobacillus than did the control and antibiotic groups (P < 0.05), whereas it decreased the number of Escherichia coli (P < 0.05). For microbial metabolites, dietary supplementation with CE increased the concentrations of lactate, total short-chain fatty acids, acetate, and butyrate in the cecum than did the control and antibiotic groups (P < 0.05), whereas it decreased the concentrations of amino acid fermentation products (ammonia, amines, p-cresol, and indole) (P < 0.05). Additionally, supplementation with CE up-regulated (P < 0.05) the mRNA expression of intestinal barrier genes (ZO-1 and Claudin) in the ileum than did both the control and antibiotic groups. However, antibiotic treatment induced gut microbiota dysbiosis, altered the microbial metabolism, and disturbed the innate immune homeostasis. In summary, these results provide evidence that dietary supplementation with CE can improve the intestinal barrier function by changing microbial composition and metabolites, likely toward a host-friendly gut environment. This suggests that CE may possibly act as an efficient antibiotic alternative for yellow-feathered broiler production.

Long-term effects of low doses of Chlorpyrifos exposure at the preweaning developmental stage: A locomotor, pharmacological, brain gene expression and gut microbiome analysis

Development is especially sensitive to Chlorpyrifos (CPF) toxicity, associated with several neurodegenerative and neurodevelopmental disorders where motor function dysfunction is a core symptom. Amongst the alternative molecular targets to cholinesterases inhibition, developmental CPF alters different components in the most important neurotransmitter systems, although this depends on the exposure period. Exposure during the late postnatal preweaning stage is the least studied by far. This period includes essential neurodevelopmental processes and has an important translational meaning. The present study analyzed the influence of low doses of CPF on this developmental window on locomotor activity and the state of the different neurotransmitter systems by pharmacological challenges. Brain gene expression and microbiome modulation following CPF were also analyzed. CPF exposure long-term increased spontaneous vertical activity, female's activity following acute stress, hyposensitized the cholinergic system and hypersensitized the GABAergic system, up-regulated both muscarinic 2 receptor and GABA-A-α2 receptor subunit in the dorsal striatum and the frontal cortex, respectively and induced gut microbiota dysbiosis at both genus and species levels. The present study supports alternative molecular targets than the ChEs following late postnatal, preweaning exposure to low doses of CPF, focusing on both cholinergic and GABAergic systems and the gut microbiome as an important factor.

Accumulation of different shapes of microplastics initiates intestinal injury and gut microbiota dysbiosis in the gut of zebrafish

Different shapes of microplastics are widely detected in the environment and organisms and most of them remain in the gut. However, the influences of shapes on the bioaccumulation and toxicity of microplastics in the gut are largely unknown. Three shapes (bead, fragment, and fiber) of microplastics of comparable size in one dimension were prepared to exposure to zebrafish. The accumulation and toxicities of microplastics in the gut were detected. Shape-dependent accumulation in the gut was observed with the order of fibers (8.0 μg/mg) > fragments (1.7 μg/mg) > beads (0.5 μg/mg). The accumulation of microplastics caused multiple toxic effects in fish intestine, including mucosal damage, and increased permeability, inflammation and metabolism disruption. Based on these toxic effects, microplastic fibers resulted in more severe intestinal toxicity than microplastic fragments and beads did. Furthermore, microplastics also induced gut microbiota dysbiosis and specific bacteria alterations, which will provide novel insights into the potential mechanism of microplastics causing intestinal toxicities in fish. Our results also suggested that shape-depended effects should not be ignored in the health risk assessment of microplastics.

Gut microbiota determines the prevention effects of Luffa cylindrica (L.) Roem supplementation against obesity and associated metabolic disorders induced by high-fat diet.

The gut microbiota, identified as the target for vegetables, can affect the development of obesity and associated metabolic syndromes. As a medicinal and edible plant, Luffa cylindrica (L.) Roem (LC) has abundant nutrients that can effectively reduce obesity risk. However, the interaction between the prevention effects of LC against obesity and the modulating gut microbiota of LC remain obscure. This study demonstrated LC supplementation improved high-fat diet (HFD)-induced gut microbiota dysbiosis and significantly enhanced short-chain fatty acid (SCFA)-producing bacteria (e.g., Blautia) along with SCFA content accumulation in the gut. Meanwhile, LC supplementation substantially restored gut barrier damage in long-term HFD treatment. Moreover, LC supplementation improved HFD-induced overweight, hyperlipidemia, insulin resistance, and chronic inflammation. Gene expression profiles showed that LC displayed an important impact on hepatic lipid transport and lipid synthesis (sterol regulatory element binding transcriptional factor 1c-peroxisome proliferator-activated receptor γ signaling pathway). More importantly, an antibiotic treatment experiment demonstrated that the beneficial effects of LC in reducing obesity risk largely depended on the gut microbiota, especially SCFA-producing bacteria (e.g., Blautia). Therefore, LC supplementation improved gut microbiota dysbiosis via enhancing SCFA-producing bacteria (e.g., Blautia), maintained gut barrier integrity, and alleviated the development of obesity. Overall, LC would provide a potential dietary intervention strategy against obesity and enteral homeostasis dysbiosis through modulating the gut microbiota.-Zhang, L., Shi, M., Ji, J., Hu, X., Chen, F. Gut microbiota determines the prevention effects of Luffa cylindrica (L.) Roem supplementation against obesity and associated metabolic disorders induced by high-fat diet.

Dietary Fructose Induced Gut Microbiota Dysbiosis is An Early Event in the Onset of Metabolic Phenotype

ObjectiveThe increased consumption of sugar‐sweetened beverages (SSBs) parallels the obesity epidemic in the United States. Dietary glucose and fructose induce divergent metabolic effects, with fructose being associated with poor metabolic outcomes. The underlying mechanism(s) remain unclear. The aim of this study is to explore whether dietary fructose and glucose instigate differential alterations of gut microbiome and the effect of short chain fatty acid‐butyrate supplementation on fructose induced alteration of gut mcirobiome.MethodsMale weanling Sprague‐Dawley rats were assigned to six groups: control, 10% glucose, 3% fructose, 10% fructose, 10% fructose plus tributyrin (Tb) and 10% fructose plus glycerol (vehicle control for Tb) (n=8/group). Rats were fed with deionized water or deionized water containing 3% fructose, 10% fructose or 10% glucose (w/v) with ad libitum access to AIN‐93G based normal chow diet for 4 weeks. Tributyrin, a prodrug of butyrate, was supplemented via oral gavage at the dose of 2g/kg body weight three times a week. Glycerol was given equal volume as vehicle control. Calorie intake, liver histology and were evaluated. The fecal microbiome was analyzed by 16S rDNA sequencing.ResultsFour weeks feeding with fructose or glucose did not result in hepatic steatosis and liver injury as shown by liver histology and plasma ALT and AST assay. However, rats fed with 10% fructose exhibited a higher body weight gain and energy efficiency ratio as well as elevated liver weight and liver/body weight ratio compared to rats fed with 10% glucose. 16S rDNA sequencing analysis showed that both 10% fructose and glucose led to a significantly decreased abundance of Firmicutes, elevated Bacteroidetes and Proteobacteria to a similar extent. Moreover, 10% fructose induced alterations of above mentioned gut microbiome can be abrogated by tributyrin supplementation. However, these alterations were not seen in 3% fructose fed rats, suggesting that fructose induced alterations of gut microbiome is related to the amount of fructose intake. In addition, the abundance of Ruminococcaceae and Lachnospiraceae, the major butyrate producers in the order of Clostridia (phylum Firmicutes) which are obligate anaerobes, showed a similar trend of decrease in both 10% fructose and glucose fed rats.ConclusionOur data clearly showed that gut microbiota dysbiosis induced by dietary sugars is an early event prior to the alterations of phenotype, highlighting the crucial role of gut microbiota in the development of metabolic syndrome. Dietary intervention to modulate gut microbiome could be a promising strategy to prevent the disease development.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 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.); the Veterans Administration (C.J.M.); and the Uof L Clinical and Translational Pilot Program (C.J.M.).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Gut microbiota characterization and lipid metabolism disorder found in PCB77-treated female mice

Although the production of polychlorinated biphenyl 77 (PCB77) has already been banned globally, PCB77 is still used for a wide range of commercial purposes. Previous evidence has demonstrated that the PCB77 administration should be responsible for the gut microbiota variations and the host health risk. However, the host disorders and bacterial functions involved in PCB77 exposure remain largely unknown. Few studies have been performed to illuminate the correlation between the bacterial functions and disorders. Furthermore, it is urgently needed to find specific strains as potential biomarkers to monitor PCB77 pollution and associated disorders. This study was designed to investigate the effects of PCB77 on gut microbiota and induced disorders in female mice. Obtained results indicated that PCB77 exposure induced gut microbiota dysbiosis, obesity, hyperlipidemia, hepatic lipid accumulation, and liver injury in mice. Functional prediction based on the phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) algorithm showed that exposure to PCB77 weakened the bacterial functions relating to lipid and energy metabolism, and immune system disease. Experimental findings were consistent with the result of the PICRUSt functional prediction. Importantly, three PCB77-associated bacterial taxa were screened out as potential biomarkers for the assessment of PCB77 pollution. This study provides previously unknown knowledge linking PCB77 administration, gut microbiota functional profile and lipid abnormalities, which is of important clinical significance for therapies treating PCB77-associated diseases.