Β-diversity Of Gut Microbiota Research Articles

Splenic nerve denervation attenuates depression-like behaviors in Chrna7 knock-out mice via the spleen–gut–brain axis

BackgroundGrowing evidence highlights the role of the spleen–brain axis in inflammation-associated depression. The α7-subtype of nicotinic acetylcholine receptor (α7 nAChR, encoded by the Chrna7 gene) is implicated in systemic inflammation, with Chrna7 knock-out (KO) mice displaying depression-like behaviors. Yet, the influence of spleen nerve on depression-like behaviors in these KO mice remains to be elucidated. MethodsWe investigated the effects of the splenic nerve denervation (SND) on depression-like behaviors, the protein expression in the prefrontal cortex (PFC), and the gut microbiota composition in Chrna7 KO mice. ResultsSND markedly alleviated depression-like behaviors and the reduced expression of GluA1 and postsynaptic density protein-95 (PSD-95) in the PFC of Chrna7 KO mice. No changes in α-diversity of gut microbiota were noted among the control, KO + sham, and KO + SND groups. However, significant differences in β-diversity of gut microbiota were noted among the groups. Notable alterations in various microbiota (e.g., Fluviimonas_pallidilutea, Maribacter_arcticus, Parvibacter_caecicola) and plasma metabolites (e.g., helicide, N-acetyl-L-aspartic acid, α-D-galactose 1-phosphate, choline, creatine) were observed between KO + sham and KO + SND groups. Interestingly, correlations were found between the relative abundance of specific microbiota and other outcomes, including synaptic proteins, metabolites and behavioral data. LimitationsThe underlying mechanisms remain to be fully understood. ConclusionsOur findings indicate that the splenic nerve contributes to depression-like phenotypes in Chrna7 KO mice via the spleen–gut–brain axis.

Characteristics of gut microbiota and its correlation with hs-CRP and somatic symptoms in first-episode treatment-naive major depressive disorder

ObjectiveMost patients with major depressive disorder (MDD) have somatic symptoms, but little studies pay attention in the microbial-inflammatory mechanisms of these somatic symptoms. Our study aimed to investigate alterations in gut microbiota and its correlation with inflammatory marker levels and somatic symptoms in first-episode treatment-naive MDD. MethodsSubjects contained 160 MDD patients and 101 healthy controls (HCs). MDD patients were divided into MDD with somatic symptoms group (MDDS) and MDD without somatic symptoms group (MDDN) based on Somatic Self-rating Scale (SSS). 16S ribosomal RNA sequencing were performed to analyze the composition of the fecal microbiota. The inflammatory factors were measured using enzyme linked immunosorbent assay (ELISA). Correlation among the altered gut microbiota, inflammatory factor and severity of clinical symptoms were analysized. ResultsRelative to HCs, MDD patients had higher levels of high-sensitivity C-reactive protein (hs-CRP) as well as disordered α-diversity and β-diversity of gut microbiota. Linear discriminant effect size (LEfSe) analysis showed that MDD patients had higher proportions of Bifidobacterium, Blautia, Haemophilus and lower proportions of Bacteroides, Faecalibacterium, Roseburia, Dialister, Sutterella, Parabacteroides, Bordetella, and Phascolarctobacterium from the genus aspect. Furthermore, correlation analysis showed Bacteroides and Roseburia had negative correlations with the hs-CRP, HAMD-24, the total and factor scores of SSS in all participants. Further, compared with MDDN, the Pielous evenness was higher in MDDS. Random Forest (RF) analysis showed 20 most important genera discriminating MDD-S and MDDN, HCs. The ROC analysis showed that the AUC was 0.90 and 0.81 combining these genera respectively. ConclusionOur study manifested MDD patients showed disordered gut microbiota and elevated hs-CRP levels, and altered gut microbiota was closely associated with hs-CRP, depressive symptoms, and somatic symptoms.

Pharmacokinetic Profiling of Ginsenosides, Rb1, Rd, and Rg3, in Mice with Antibiotic-Induced Gut Microbiota Alterations: Implications for Variability in the Therapeutic Efficacy of Red Ginseng Extracts.

Ginsenoside Rg3 is reported to contribute to the traditionally known diverse effects of red ginseng extracts. Significant individual variations in the therapeutic efficacy of red ginseng extracts have been reported. This study aimed to investigate the effect of amoxicillin on the pharmacokinetics of ginsenosides Rb1, Rd, and Rg3 in mice following the oral administration of red ginseng extracts. We examined the α-diversity and β-diversity of gut microbiota and conducted pharmacokinetic studies to measure systemic exposure to ginsenoside Rg3. We also analyzed the microbiome abundance and microbial metabolic activity involved in the biotransformation of ginsenoside Rb1. Amoxicillin treatment reduced both the α-diversity and β-diversity of the gut microbiota and decreased systemic exposure to ginsenoside Rg3 in mice. The area under the curve (AUC) values for Rg3 in control and amoxicillin-treated groups were 247.7 ± 96.6 ng·h/mL and 139.2 ± 32.9 ng·h/mL, respectively. The microbiome abundance and microbial metabolic activity involved in the biotransformation of ginsenoside Rb1 were also altered by amoxicillin treatment. The metabolizing activity was reduced from 0.13 to 0.05 pmol/min/mg on average. Our findings indicate that amoxicillin treatment potentially reduces the gut-microbiota-mediated metabolism of ginsenoside Rg3 in mice given red ginseng extracts, altering its pharmacokinetics. Gut microbiome variations may thus influence individual ginsenoside pharmacokinetics, impacting red ginseng extract's efficacy. Our results suggest that modulating the microbiome could enhance the efficacy of red ginseng.

Differential Gut Microbiota, Dietary Intakes in Constipation Patients with or without Hypertension.

Diet and gut microbiota are involved in blood pressure regulations, but few studies have focused on the constipation patients. The study seeks to identify differences in gut microbiota between hypertensive and normotensive subjects in constipation patients, analyzes the relationship between dietary patterns and blood pressure, and explores mediation effects of gut microbiota. Gut microbial genera and dietary information of 186 functional constipation participants are characterized by 16S rRNA sequencing and a food frequency questionnaire. The hypertensive subjectsshows lower α-diversity and β-diversity of gut microbiota than normotensive (p < 0.05) and 17 differential microbial genera. The dried-beans intake frequency inversely correlated with systolic and diastolic blood pressure after multivariate adjustment (r = -0.273, p-FDR < 0.01; r = -0.251, p-FDR = 0.026, respectively). Logistic regression indicates that the individuals often consumed dried-beans have a lower hypertension risk than those never consumed [OR = 0.137, 95% CI: (0.022, 0.689), p = 0.022]. A marginal mediating effect of the genus Monoglobus is observed for the association between high-fiber dietary pattern and hypertension. In patients with functional constipation, hypertension-related gut microbial differences are identified. Dried-beans intake is inversely associated with blood pressure, and a genus may potentially mediate the association between high-fiber dietary pattern and hypertension.

Does PM1 exposure during pregnancy impact the gut microbiota of mothers and neonates?

BackgroundAmbient air pollutant exposure can change the composition of gut microbiota at 6-months of age, but there is no epidemiological evidence on the impacts of exposure to particulate matter with an aerodynamic diameter ≤1 μm (PM1) during pregnancy on gut microbiota in mothers and neonates. We aimed to determine if gestational PM1 exposure is associated with the gut microbiota of mothers and neonates. MethodsLeveraging a mother-infant cohort from the central region of China, we estimated the exposure concentrations of PM1 during pregnancy based on residential address records. The gut microbiota of mothers and neonates was analyzed using 16 S rRNA V3–V4 gene sequences. Functional pathway analyses of 16 S rRNA V3–V4 bacterial communities were conducted using Tax4fun. The impact of PM1 exposure on α-diversity, composition, and function of gut microbiota in mothers and neonates was evaluated using multiple linear regression, controlling for nitrogen dioxide (NO2) and ozone (O3). Permutation multivariate analysis of variance (PERMANOVA) was used to analyze the interpretation degree of PM1 on the sample differences at the OTU level using the Bray-Curtis distance algorithm. ResultsGestational PM1 exposure was positively associated with the α-diversity of gut microbiota in neonates and explained 14.8% (adj. P = 0.026) of the differences in community composition among neonatal samples. In contrast, gestational PM1 exposure had no impact on the α- and β-diversity of gut microbiota in mothers. Gestational PM1 exposure was positively associated with phylum Actinobacteria of gut microbiota in mothers, and genera Clostridium_sensu_stricto_1, Streptococcus, Faecalibacterium of gut microbiota in neonates. At Kyoto Encyclopedia of Genes and Genomes pathway level 3, the functional analysis results showed that gestational PM1 exposure significantly down-regulated Nitrogen metabolism in mothers, as well as Two-component system and Pyruvate metabolism in neonates. While Purine metabolism, Aminoacyl-tRNA biosynthesis, Pyrimidine metabolism, and Ribosome in neonates were significantly up-regulated. ConclusionsOur study provides the first evidence that exposure to PM1 has a significant impact on the gut microbiota of mothers and neonates, especially on the diversity, composition, and function of neonatal meconium microbiota, which may have important significance for maternal health management in the future.

Long-lasting beneficial effects of maternal intake of sulforaphane glucosinolate on gut microbiota in adult offspring

Mounting evidence suggests the impact of maternal diet on the health of offspring. We reported that maternal diet of sulforaphane glucosinolate (SGS) could prevent behavioral abnormalities in offspring after maternal immune activation. The present study was designed to investigate whether the dietary intake of SGS during pregnancy and lactation influences the composition of gut microbiota in the offspring. The dietary intake of SGS during pregnancy and lactation caused significant changes in the α-diversity and β-diversity of gut microbiota in 3-week-old offspring (SGS-3W group) and 10-week-old offspring (SGS-10W group). The LEfSe algorithm identified several microbes as important phylotypes in the SGS-3W or SGS-10W groups. Predictive functional metagenomes showed that the maternal intake of SGS caused several KEGG pathways alterations with respect to the genetic information processing and metabolism. Furthermore, the plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the SGS-10W group after the injection of lipopolysaccharide (LPS: 0.5 mg/kg) were significantly lower than those of the CON-10W group. It is noteworthy that there were positive correlations between the relative abundance of the genus Blautia and IL-6 (or TNF-α) in adult offspring. Moreover, there were sex differences of gut microbiota composition in offspring. In conclusion, these data suggest that the dietary intake of SGS during pregnancy and lactation might produce long-lasting beneficial effects in adult offspring through the persistent modulation of gut microbiota. It is likely that the modulation of gut microbiota by maternal nutrition may confer resilience versus vulnerability to stress-related psychiatric disorders in the offspring.

Gut microbiota mediate melatonin signalling in association with type 2 diabetes.

It has been shown that melatonin plays a general beneficial role in type 2 diabetes in rodents but its role in humans is controversial. In the present study, we investigated the association between serum melatonin and type 2 diabetes risk in a southern Chinese population in a case-control study. We also examined the role of gut microbiota in this relationship. Individuals with type 2 diabetes (cases) and healthy individuals (controls) (n=2034) were recruited from a cross-sectional study and were matched for age and sex in a case-control study. The levels of serum melatonin were measured and the association between serum melatonin and type 2 diabetes risk was examined using a multivariable logistic regression model. We further conducted a rigorously matched case-control study (n=120) in which gut microbial 16S rRNA was sequenced and metabolites were profiled using an untargeted LC-MS/MS approach. Higher levels of serum melatonin were significantly associated with a lower risk of type 2 diabetes (OR 0.82 [95% CI 0.74, 0.92]) and with lower levels of fasting glucose after adjustment for covariates (β -0.25 [95% CI -0.38, -0.12]). Gut microbiota exhibited alteration in the individuals with type 2 diabetes, in whom lower levels of serum melatonin, lower α- and β-diversity of gut microbiota (p<0.05), greater abundance of Bifidobacterium and lower abundance of Coprococcus (linear discriminant analysis [LDA] >2.0) were found. Seven genera were correlated with melatonin and type 2 diabetes-related traits; among them Bifidobacterium was positively correlated with serum lipopolysaccharide (LPS) and IL-10, whereas Coprococcus was negatively correlated with serum IL-1β, IL-6, IL-10, IL-17, TNF-α and LPS (Benjamini-Hochberg-adjusted p value [false discovery rate (FDR)] <0.05). Moreover, altered metabolites were detected in the participants with type 2 diabetes and there was a significant correlation between tryptophan (Trp) metabolites and the melatonin-correlated genera including Bifidobacterium and Coprococcus (FDR<0.05). Similarly, a significant correlation was found between Trp metabolites and inflammation factors, such as IL-1β, IL-6, IL-10, IL-17, TNF-α and LPS (FDR<0.05). Further, we showed that Trp metabolites may serve as a biomarker to predict type 2 diabetes status (AUC=0.804). A higher level of serum melatonin was associated with a lower risk of type 2 diabetes. Gut microbiota-mediated melatonin signalling was involved in this association; especially, Bifidobacterium- and Coprococcus-mediated Trp metabolites may be involved in the process. These findings uncover the importance of melatonin and melatonin-related bacteria and metabolites as potential therapeutic targets for type 2 diabetes.

Gut Microbiota Mediate Melatonin Signaling in Association With Type 2 Diabetes

ObjectivesTo investigate the association between serum melatonin (MT) and type 2 diabetes (T2D) risk in southern Chinese population in a case-control study as well as the role of gut microbiota in the relationship between them.MethodsT2D cases and healthy controls (n = 2034) were recruited from a cross-sectional study and matched age and sex for a case-control study, and the association between serum MT and T2D risk was examined using a multivariable logistic regression model. We further conducted a rigorously matched case-control study (n = 120), in which gut microbial 16S RNA was sequenced and metabolites were profiled using an untargeted LC-MS/MS approach.ResultsHigher levels of serum MT were significantly associated with a lower risk of T2D (OR = 0.84; 95% CI 0.75–0.93) and with lower levels of fasting glucose after adjustment for covariates (β = −0.21; 95% CI −0.33, −0.09). T2D patients exhibited lower levels of serum MT, lower α- and β-diversity of gut microbiota (p < 0.05), greater abundance of Bifidobacterium and lower abundance of Coprococcus (LDA > 2.0). Seven genera were correlated with MT and T2D related traits, among them Bifidobacterium was positively correlated with serum LPS and IL-10, whereas Coprococcus was negatively correlated with serum IL-1β, IL-6, IL-10, IL-17, INF-α and LPS (FDR < 0.05). Moreover, altered metabolites were detected in the T2D patients, and there was a significant correlation between tryptophan (Trp) metabolites and the melatonin-correlated genera including Bifidobacterium and Coprococcus (FDR < 0.05). A significant correlation also was found between Trp metabolites and inflammation factors, such as IL-1β, IL-6, IL-10, IL-17, INF-α and LPS (FDR < 0.05). Further, we showed that Trp metabolites may serve as a biomarker to predict T2D status (AUC = 0.804).ConclusionsHigher level of serum MT was associated with lower risk of T2D, and that gut microbiota-mediated MT signaling was involved in this association, especially, Bifidobacterium and Coprococcus mediated Trp metabolites may be involved in the process. These findings uncover the importance of MT and MT-related bacteria and metabolites as potential therapeutic targets for T2D.Funding SourcesThis work was supported by the National Natural Science Foundation of China (No.82060593), Natural Science Foundation of Guangxi Province (No. 2018GXNSFDA050019).

Alterations and Correlations of Gut Microbiota and Fecal Metabolome Characteristics in Experimental Periodontitis Rats.

ObjectivesPeriodontitis affects the progression of many diseases, while its detailed mechanism remains unclear. This study hopes to provide new ideas for exploring its mechanism by analyzing the gut microbiota and fecal metabolic characteristics of experimental periodontitis rats.MethodsA total of 10 rats were randomly divided into ligature-induced experimental periodontitis (EP) group and healthy control group. After 4 weeks of the experiment, the feces of all rats were collected for sequencing through 16S ribosomal DNA (rDNA) sequencing technology and liquid chromatography–mass spectrometry (LC–MS).Results16S rDNA sequencing results showed that the β-diversity of gut microbiota was significantly different between the EP and control group, and the levels of dominant genera were different. Compared with the control group, Ruminococcus, Escherichia, and Roseburia were significantly enriched in EP, and Coprococcus, Turicibacter, Lachnospira were significantly decreased. Correlation analysis showed that Roseburia exhibited the highest correlation within the genus. Of 3,488 qualitative metabolites, 164 metabolites were upregulated and 362 metabolites were downregulated in EP. Enrichment analysis showed that periodontitis significantly changed 45 positive/negative ion metabolic pathways. Five KEGG pathways, protein digestion and absorption, tyrosine metabolism, glycolysis/gluconeogenesis, niacin and nicotinamide metabolism, and oxidative phosphorylation, are enriched in both the microbiome and metabolome. Correlation analysis showed that the genera with significant differences in periodontitis were usually significantly correlated with more metabolites, such as Roseburia, Lachnospira, Escherichia, Turicibacter, and Ruminococcus. The genera with the same changing trend tended to have a similar correlation with some certain metabolites. In addition, vitamin D2 and protoporphyrin IX have the most significant correlations with microorganisms.ConclusionOur study reveals that periodontitis alters gut microbiota and fecal metabolites. The correlation analysis of microbiota and metabolome provides a deeper understanding of periodontitis, and also provides a direction for the study of periodontitis affecting other diseases.

Effect of Different Dietary Selenium Sources on Growth Performance, Antioxidant Capacity, Gut Microbiota, and Molecular Responses in Pacific White Shrimp Litopenaeus vannamei

This study investigated the effect of different dietary selenium (Se) sources on the growth performance, antioxidant capacity, gut microbiota, and molecular responses of the Pacific white shrimp Litopenaeus vannamei. Four Se sources (sodium selenite, L-selenomethionine, selenium yeast, or Se nanoparticles) were added to purified diets to 0.4 mg Se/kg diet for shrimp ( 1.60 ± 0.14 g ). Each treatment was randomly assigned to 3 replicated tanks and 30 shrimp in each tank (500 L). After 8 weeks of breeding, L-selenomethionine and selenium yeast significantly increased weight gain compared with sodium selenite treatment, while sodium selenite significantly decreased the shrimp hepatosomatic index compared with the other groups. The L-selenomethionine significantly increased the superoxide dismutase and glutathione peroxidase activities in the hepatopancreas compared with the shrimp fed sodium selenite and decreased catalase activity and malondialdehyde content compared with other groups. The composition and β-diversity of gut microbiota were markedly changed in each group. The abundances of Rubrobacter and Rubritalea, Winogradskyella and Motilimonas, and Photobacterium in the gut microbiota were specially altered by L-selenomethionine, Se yeast, and Se nanoparticles, respectively. The sodium selenite group showed lower complexity of gut interspecies interactions. RNA-seq analysis showed that “arachidonic acid metabolism”-related genes were significantly enriched in the L-selenomethionine and Se yeast groups; “peroxisome” and “drug metabolism–other enzymes”-related genes were enriched in the Se nanoparticle group. Vibrio, Motilimonas, and Photobacterium were associated with amino acid and lipid metabolism. Pseudoalteromonas, Silicimonas, Roseovarius, and Halomonas inhibited the expression of glutathione peroxidase genes. These results suggested that organic Se, especially selenomethionine, is an effective feed supplement to promote growth and antioxidant capacity, maintain the health of gut microbiota, and promote the utilization of fatty acid and glutathione peroxidase genes in shrimp fed a 0.4 mg Se/kg diet.

Regulation of neurotoxicity in the striatum and colon of MPTP-induced Parkinson’s disease mice by gut microbiome

Increasing evidence suggests the role of gut–microbiota–brain axis in the pathogenesis of Parkinson’s disease (PD). The objective of this study was to examine whether repeated administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) can influence the neurotoxicity in the striatum and colon, and the composition of gut microbiota and short-chain fatty acids (SCFAs) in feces of adult mice. MPTP caused the reduction of dopamine transporter (DAT) and tyrosine hydroxylase (TH) in the striatum, and increases in phosphorylated α-synuclein (p-α-Syn) in the striatum and colon. There was a negative correlation between the expression of TH in the striatum and the expression of p-α-Syn in the colon, suggesting a role of gut–brain communication. MPTP caused abnormalities in the α- and β-diversity of gut microbiota in the mice. Furthermore, the relative abundance of the genus Faecalicatena in the MPTP-treated group was significantly lower than that of control group. Interestingly, there was a positive correlation between the genus Faecalicatena and the expression of TH in the striatum. Moreover, MPTP did not alter the levels of SCFAs in feces samples. However, there was a positive correlation between the relative abundance of the genus Faecalicatena and propionic acid. The data suggest that MPTP-induced increases in colonic p-α-Syn expression might be associated with dopaminergic neurotoxicity in the striatum via gut–microbiota–brain axis.

Abnormalities in the composition of the gut microbiota in mice after repeated administration of DREADD ligands

Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are known as genetically modified G-protein-coupled receptors (GPCRs), which can be activated by synthetic ligands such as clozapine N-oxide (CNO) and DREADD agonist 21 (compound 21: C21). The brain-gut-microbiota axis has a crucial role in bidirectional interactions between the brain and the gastrointestinal microbiota. In this study, we investigated whether repeated administration of CNO or C21 could influence the gut microbiota and short-chain fatty acids (SCFAs) in feces of adult mice. Repeated administration of CNO or C21 as drinking water did not alter the α- and β-diversity of gut microbiota in mice compared with control mice. However, we found significant changes in relative abundance for several bacteria in the CNO (or C21) group at the taxonomic level compared to the control group. The linear discriminant analysis effect size (LEfSe) algorithm distinguished the family Prevotellaceae, the genus Anaerocolumna, the genus Prevotella, and the genus Frisingicoccus, these four specific microbial markers for the CNO group relative to the control group. In addition, the LEfSe algorithm identified the family Clostridiaceae, the genus Faecalicatena and the genus Marinisporobacter, these three bacteria of different taxonomic as potential microbial markers for the C21 group relative to the control group. In contrast, repeated administration of CNO (or C21) did not alter SCFAs in feces samples of adult mice. The data suggest that repeated administration of CNO or C21 contributes to an unusual organization of the gut microbiota in adult mice. Therefore, abnormalities in the composition of gut microbiota by repeated dosing of DREADD ligands should be taken into consideration for behavioral and biological functions in rodents treated with DREADD ligands.

Inulin alleviates hypersaline-stress induced oxidative stress and dysbiosis of gut microbiota in Nile tilapia (Oreochromis niloticus)

This study explored the alleviation of salinity-induced stress by adding dietary prebiotic inulin in Nile tilapia Oreochromis niloticus. Tilapias were administrated with four levels of inulin (0, 0.2%, 0.4% and 0.8%) at the salinity of 16 psu (practical salinity unit) for 8 weeks, and meanwhile the tilapia fed the basal diet in freshwater were served as a freshwater control. The final weight, weight gain, and specific growth rate increased but feed conversion ratio decreased in the 16 psu group compared to the freshwater group. These trends became more evident in groups of 16 psu + 0.2% inulin and 16 psu + 0.4% inulin, and the best growth was obtained in the 16 psu + 0.4% inulin group. SOD activity was significantly elevated while CAT and GST activities were markedly reduced in 16 psu group compared to the freshwater group, but these parameters returned to the freshwater group level when tilapia were fed with 0.4% inulin. Amylase and protease activities were significantly increased in 16 psu group compared to the freshwater group, but reduced and returned to the level of freshwater group by adding 0.2% and 0.4% inulin to the diet. The composition, α-diversity, and β-diversity of gut microbiota were disturbed in 16 psu group, but returned to the freshwater group pattern in 16 psu + 0.8% inulin group. The results show that dietary inulin is an effective feed additive to alleviate the oxidative stress and gut microbiota dysbiosis at 16 psu. This study suggests that dietary manipulation using inulin is a promising strategy to improve fish healthy under saline stress, and the optimal level of inulin supplementation to the diet is 0.4% for Nile tilapia at 16 psu.

Effect of probiotics during vonoprazan-containing triple therapy on gut microbiota in Helicobacter pylori infection: A randomized controlled trial.

Probiotics are beneficial to patients with Helicobacter pylori infections by modulating the gut microbiota. Biofermin-R (BFR) is a multiple antibiotic-resistant lactic acid bacteria preparation of Enterococcus faecium 129 BIO 3B-R and is effective in normalizing the gut microbiota when used in combination with antibiotics. This study aimed to determine the effect of BFR in combination with vonoprazan (VPZ)-based therapy on gut microbiota. Patients with positive urinary anti-H pylori antibody test (primary test) and fecal H pylori antigen test (secondary test) were examined. Patients in group 1 (BFR- ) received VPZ (20mg twice daily), amoxicillin (750mg twice daily), and clarithromycin (400mg twice daily) for 7days. Patients in group 2 (BFR+ ) received BFR (3 tablets/day) for 7days, in addition to the aforementioned treatments. Following treatment, the relative abundance, α-diversity, and β-diversity of gut microbiota were assessed. Supplementation with BFR prevented the decrease in a-diversity after eradication therapy (Day 7). β-diversity was similar between groups. The incidence rate of diarrhea was non-significantly higher in the BFR- than in the BFR+ group (73.1% vs 56.5%; P=.361). Stool consistency was comparable in the BFR+ group on Days 7 and 1 (3.86±0.95 vs 3.86±1.46; P=.415). Biofermin-R combined with VPZ-based therapy resulted in higher microbial α-strain diversity and suppressed stool softening during H pylori eradication therapy.

DOP36 Family-specific host genetic and gut microbial signatures have a beneficial role in early identification of familial inflammatory bowel diseases

Abstract Background Familial IBD may have its own signatures with respect to host genetic variants and/or gut microbiome. However, available data focussing on this topic is still limited, particularly for Asian patients with familial IBD. We aimed to investigate the possible host genetic and gut microbial signatures in familial IBD through a combined analysis of genomic and metagenomic profiles. Methods All patients were affiliated with a prospectively recruited cohort of patients with IBD (NCT03589183) and met the diagnostic criteria of Crohn’s disease (CD) or ulcerative colitis (UC). We constructed a unique family cohort comprising ≥2 affected individuals with familial IBD and ≥1 their unaffected, healthy first-degree relative (FDR) in each family. Whole-exome sequencing for rare variants followed by a genome-wide single-nucleotide polymorphism analysis for common variants was performed. A polygenic risk score (PRS) was calculated separately in Crohn’s disease (CD), ulcerative colitis (UC) or IBD. Gut microbial community was analysed by 16s rRNA sequencing of stool samples. Results Eight Korean families comprising 16 with familial IBD (12 concordant IBD, 4 discordant IBD) and 9 FDRs were included for analysis. Whole-exome sequencing identified four family-specific candidate genes (LAMA5, MYO15B, TTN, and WDR66) with rare missense variants that were transmitted preferentially to the affected FDRs in at least ≥3 families (Figure 1). An in silico analysis identified the deleterious effect of the identified variants on the gene products including LAMA5 (SIFT = 0, PolyPhen-2 = 0.72). The patients with CD, but not those with UC, had a significantly higher mean PRS than controls (PRS = 2.137 vs. 0.742, p-value = 0.030). Metagenomic sequencing revealed significant differences in α- and β-diversity of gut microbiota among the patients with CD, those with UC, and unaffected FDRs (all p &amp;lt; 0.05), showing lower microbial richness in the patients with familial IBD (p = 0.02). In various taxonomic levels, compared with unaffected FDRs, the patients with familial IBD showed the significantly differential abundance of several gut bacteria (all corrected p &amp;lt; 0.05; Figure 2). Conclusion Family-specific host genetic and gut microbial signatures have a beneficial role in early-identification of familial IBD (NCT03515070).

Moderate-intensity aerobic and resistance exercise is safe and favorably influences body composition in patients with quiescent Inflammatory Bowel Disease: a randomized controlled cross-over trial

BackgroundOverweight and metabolic problems now add to the burden of illness in patients with Inflammatory Bowel Disease. We aimed to determine if a program of aerobic and resistance exercise could safely achieve body composition changes in patients with Inflammatory Bowel Disease.MethodsA randomized, cross-over trial of eight weeks combined aerobic and resistance training on body composition assessed by Dual Energy X-ray Absorptiometry was performed. Patients in clinical remission and physically inactive with a mean age of 25 ± 6.5 years and Body Mass Index of 28.9 ± 3.8 were recruited from a dedicated Inflammatory Bowel Disease clinic. Serum cytokines were quantified, and microbiota assessed using metagenomic sequencing.ResultsImproved physical fitness was demonstrated in the exercise group by increases in median estimated VO2max (Baseline: 43.41mls/kg/min; post-intervention: 46.01mls/kg/min; p = 0.03). Improvement in body composition was achieved by the intervention group (n = 13) with a median decrease of 2.1% body fat compared with a non-exercising group (n = 7) (0.1% increase; p = 0.022). Lean tissue mass increased by a median of 1.59 kg and fat mass decreased by a median of 1.52 kg in the exercising group. No patients experienced a deterioration in disease activity scores during the exercise intervention. No clinically significant alterations in the α- and β-diversity of gut microbiota and associated metabolic pathways were evident.ConclusionsModerate-intensity combined aerobic and resistance training is safe in physically unfit patients with quiescent Inflammatory Bowel Disease and can quickly achieve favourable body compositional changes without adverse effects.Trial registrationThe study was registered at ClinicalTrials.gov; Trial number: NCT02463916.

Abstract 398: Gut Microbiota Facilitates Apolipoprotein A1 and HDL Production Through Hepatic TLR5

Gut microbiota is considered as an external organ as these trillions of commensal microbes in our gut interact with our body to regulate various physiological responses. The pattern and composition of gut bacteria is subject to alteration by our diet. High fat diet not only decreases the β-diversity of gut microbiota but also increases gut permeability, leading to the leak of bacterial products into circulation, which aggravates various diseases including atherosclerosis by escalating inflammation. Paradoxically high fat intake can augment HDL level (J Clin Invest 91:1665-71, 1993). Moreover, gut microbiota was shown to contribute the variation of HDL but not LDL or total cholesterol level in a human study. (Circ Res 117: 817-24, 2015) We speculate that gut microbiota may provide an adaptive protection by upregulating HDL level. In this study, we investigated the possible underlying mechanism of how gut microbiota affects HDL level. C57BL/6J mice were fed a normal chow diet and a high fat diet (HFD, 45% fat kcal) for 10 weeks. Other than decreasing the β-diversity of gut microbiota, HFD increased the portion of flagellated bacteria, resulting in the increase of hepatic but not circulating level of flagellin, the ligand of toll-like receptor (TLR5). Deletion of TLR5 in mice suppressed HFD-stimulated HDL level. Treatment with flagellin in hepatocytes was able to stimulate apolipoprotein A1 (apoA), the primary apolipoprotein on HDL in TLR5-dependent manner. Blocking the downstream signaling of TLR5 by silencing MYD88 blocked the flagellin-induced apoA1 production in wild type hepatocytes. Lipopolysaccharides, another important bacterial product which can activate MYD88 signaling, failed to elicit the same effect. It might be due to the different degree of sensitivity of these TLRs in hepatocytes. In addition, supplementation of flagellin to atherogenic mice (apoE knockout mice) by oral gavage was able to elevate apoA1 and HDL levels in circulation, partially protecting against atherosclerosis. Our data provides a molecular explanation of how commensal bacteria in gut stimulate HDL production upon HFD, and such finding will provide an insight in developing alternative strategy to stimulate HDL production and prevent atherosclerosis.