Kang-Xian Pills Inhibit Inflammatory Response and Decrease Gut Permeability to Treat Carbon Tetrachloride-Induced Chronic Hepatic Injury through Modulating Gut Microbiota

Kang-Xian (KX) pills have been clinically used for the treatment of chronic hepatic injury (CHI). However, the mechanisms of KX on CHI remain unknown. The aim of this study mainly focused on the anti-inflammatory effects of KX in a CHI mouse model based on modulating gut microbiota and gut permeability. We first established a CHI model using carbon tetrachloride (CCl4) and treated it with KX. The anti-inflammatory effects of KX on CHI model mice and the changes in gut permeability after KX treatment were also investigated. 16S rRNA analysis was used to study the changes of gut microbiota composition after KX treatment. In addition, gut microbiota was depleted using a combination of antibiotics in order to further confirm that KX could inhibit the inflammatory response and decrease gut permeability to treat CHI by modulating the gut microbiota. Results showed that KX treatment significantly improved liver function in CHI model mice. KX could also increase the levels of tight junction proteins in the colon and decrease the expression of proinflammatory cytokines in the liver. 16S rRNA analysis indicated that KX treatment affected the alpha and beta diversities in CHI model mice. Further analysis of 16S rRNA sequencing indicated that KX treatment increased the ratio of Firmicutes to Bacteroidetes at the phylum level. At the genus level, KX treatment increased the relative abundance of Lactobacillus, Bacteroides, and Akkermansia and decreased the relative abundance of Ralstonia, Alloprevotella, and Lachnoclostridium. However, KX could not alleviate CHI after depleting the gut microbiota. The effects of KX on gut permeability and inflammatory response in the liver were also decreased following the depletion of gut microbiota. In conclusion, our current study demonstrated that gut microbiota was significantly affected during CHI progression. KX could inhibit the inflammatory response and decrease the gut permeability in CHI model mice through modulating the gut microbiota.

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Jian-Gan-Xiao-Zhi Decoction Alleviates Inflammatory Response in Nonalcoholic Fatty Liver Disease Model Rats through Modulating Gut Microbiota

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/5522755 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Jiabao Liao ◽

Xuehua Xie ◽

Jinmei Gao ◽

Zhaiyi Zhang ◽

Fei Qu ◽

...

Keyword(s):

Liver Disease ◽

16S Rrna ◽

Inflammatory Response ◽

Gut Microbiota ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Gut Permeability ◽

16S Rrna Analysis ◽

Nonalcoholic Fatty Liver ◽

Tnf Α

Background. Jian-Gan-Xiao-Zhi decoction (JGXZ), composed of Salvia miltiorrhiza Bunge, Panax notoginseng, Curcuma zedoaria, and other 9 types of herbs, has demonstrated beneficial effects on nonalcoholic fatty liver disease (NAFLD). However, the mechanisms behind JGXZ’s impact on NAFLD remain unknown. Methods. In this study, a NAFLD rat model induced by a high-fat diet (HFD) received oral treatment of JGXZ (8 or 16 g crude herb/kg) for 12 weeks. The therapeutic effects of JGXZ on NAFLD model rats were investigated through blood lipid levels and pathological liver changes. 16S rRNA analysis was used to study the changes in gut microbiota after JGXZ treatment. The expressions of occludin and tight junction protein 1 (ZO-1) in the colon were investigated using immunostaining to study the effects of JGXZ on gut permeability. The anti-inflammatory effects of JGXZ were also studied through measuring the levels of IL-1β, IL-6, and TNF-α in the serum and liver. Results. JGXZ treatment could decrease body weight and ameliorate dyslipidemia in NAFLD model rats. H&E and Oil Red O staining indicated that JGXZ reduced steatosis and infiltration of inflammatory cells in the liver. 16S rRNA analysis showed that JGXZ impacted the diversity of gut microbiota, decreasing the Firmicutes–to-Bacteroidetes ratio, and increasing the relative abundance of probiotics, such as Alloprevotella, Lactobacillus, and Turicibacter. Gut permeability evaluation found that the expressions of ZO-1 and occludin in the colon were increased after JGXZ treatment. Moreover, JGXZ treatment could decrease the levels of IL-1β, IL-6, and TNF-α in the serum and liver. Conclusions. Our study illustrated that JGXZ could ameliorate NAFLD through modulating gut microbiota, decreasing gut permeability, and alleviating inflammatory response.

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Effects of Industrial and Ruminant Trans-fatty Acids-Enriched Diet on Fecal Microbiome and Short Chain Fatty Acid Metabolites of C57BL/6 Mice

Current Developments in Nutrition ◽

10.1093/cdn/nzab054_026 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 1171-1171

Author(s):

Farzad Mohammadi ◽

Emma Tolsdorf ◽

Karine Greffard ◽

Élodie Chotard ◽

Jean-François Bilodeau ◽

...

Keyword(s):

Fatty Acids ◽

16S Rrna ◽

Gut Microbiota ◽

Butyric Acid ◽

Relative Abundance ◽

Trans Fatty Acids ◽

Valeric Acid ◽

Short Chain ◽

16S Rrna Analysis ◽

Fecal Microbiome

Abstract Objectives We hypothesized that the intake of industrially originated trans-fatty acids (elaidic acid (EA trans 18: 1n-9)) and ruminant trans fatty acids (trans-palmitoleic acid (TPA t16:1 n-7)) will differentially modify gut microbiota and short-chain fatty acids (SCFA) profiles. The objective is to compare the long- and short-term effects of EA and TPA on the fecal microbiome and SCFAs profiles in mice. Methods Forty C57BL/6 mice were divided to 4 groups. Each group was given one of the following 4 formulations in the drinking water: lecithin nanovesicles, nanovesicles containing either lecithin with EA or TPA (86:14 (w/w)) or water alone (control) for 28 days with a normal fat diet. Fecal samples were collected at days 0, 7 and 28. Gut microbiota profiles were determined by 16S rRNA gene sequencing. SCFAs were measured by headspace gas chromatography coupled to a single quadrupole mass spectrometer. Baseline data (relative abundance of bacteria or levels of SCFAs) was pooled and then compared with data from day 7 or day 28 for each formulation. Results After 7 days of lecithin, 16S rRNA analysis revealed an increase in the relative abundance of Lactobacillus. After 28 days of lecithin, an increase in the relative abundance of Lactobacillus, Erysipelotrichaceae, and Enterobacteriaceae together with a decrease in Bacteroidaceae was observed. Further, a tendency to increase level of butyric acid (P = 0.053) was observed after 28 days of lecithin. After 7 days of EA, an increase in the relative abundance of Lactobacillus, whereas a decrease in the relative abundance of Parabacteroides, Bacteroides, Rumininococcaceae, Lachnospiraceae and Peptococcaceae was observed. After 7 days of TPA, results show a decreased level of isovaleric acid (P = 0.04) and valeric acid (P = 0.03). After 28 days of TPA, data demonstrates an increase in the level of butyric acid (P = 0.01) and propionic acid (P = 0.01). Water intake for 28 days decreased the level of valeric acid (P = 0.02). Conclusions Consumption of industrial and ruminant trans-fatty acids modify differentially bacterial taxa present in the gut microbiome and SCFA profiles. Funding Sources NSERC, CMDO.

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Jian-Gan-Xiao-Zhi Decoction Ameliorates Nonalcoholic Fatty Liver Disease Through Modulating Gut Microbiota, Decreasing Gut Permeability, and Alleviating Liver Inflammation

10.21203/rs.3.rs-122886/v1 ◽

2020 ◽

Author(s):

Jiabao Liao ◽

Xuehua Xie ◽

Jinmei Gao ◽

Zhaiyi Zhang ◽

Fei Qv ◽

...

Keyword(s):

Liver Disease ◽

16S Rrna ◽

Gut Microbiota ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Liver Inflammation ◽

Gut Permeability ◽

16S Rrna Analysis ◽

Nonalcoholic Fatty Liver ◽

Tnf Α

Abstract BackgroundJian-Gan-Xiao-Zhi decoction (JGXZ), composed of Salvia miltiorrhiza Bunge, Panax notoginseng, Curcuma zedoaria, and other 9 types of herbs, has demonstrated beneficial effects on nonalcoholic fatty liver disease (NAFLD). However, the mechanisms behind JGXZ’s impact on NAFLD remain unknown. MethodsIn this study, a NAFLD rat model induced by a high-fat diet (HFD) received oral treatment of JGXZ (8 or 16 g crude herb/kg) for 8 weeks. The therapeutic effects of JGXZ on NAFLD model rats were investigated through blood lipid levels and pathological liver changes. 16s rRNA analysis was used to study the changes in gut microbiota after JGXZ treatment. The expressions of occludin and tight junction protein 1 (ZO-1) in colon were investigated using immunostaining to study the effects of JGXZ on gut permeability. The anti-inflammatory effects of JGXZ were also studied through measuring the levels of IL-1β, IL-6 and TNF-α in serum and liver.ResultsJGXZ treatment could decrease body weight and ameliorate dyslipidemia in NAFLD model rats. H&E and Oil Red O staining indicated that JGXZ reduced steatosis and infiltration of inflammatory cells into the liver. 16s rRNA analysis exhibited that JGXZ impacted the diversity of gut microbiota, decreasing the Firmicutes to Bacteroidetes ratio and increasing the relative abundance of probiotics, such as Alloprevotella, Lactobacillus, and Turicibacter. Gut permeability evaluation found that the expressions of ZO-1 and occludin in the colon were increased after JGXZ treatment, and inflammation analysis showed decreased levels of IL-1β, IL-6, and TNF-α in the serum and liver after treatment. ConclusionsOur study illustrates that JGXZ ameliorates NAFLD through modulating gut microbiota, decreasing gut permeability, and alleviating liver inflammation.

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Impact of a probiotic, inulin, or their combination on the piglets’ microbiota at different intestinal locations

Beneficial Microbes ◽

10.3920/bm2014.0030 ◽

2015 ◽

Vol 6 (4) ◽

pp. 473-483 ◽

Cited By ~ 10

Author(s):

V.A. Sattler ◽

K. Bayer ◽

G. Schatzmayr ◽

A.G. Haslberger ◽

V. Klose

Keyword(s):

16S Rrna ◽

Gut Microbiota ◽

16S Rrna Gene ◽

Real Time ◽

Relative Abundance ◽

Real Time Pcr ◽

Denaturing Gradient Gel Electrophoresis ◽

Feed Additives ◽

Rrna Gene ◽

16S Rrna Gene Pyrosequencing

Natural feed additives are used to maintain health and to promote performance of pigs without antibiotics. Effects of a probiotic, inulin, and their combination (synbiotic), on the microbial diversity and composition at different intestinal locations were analysed using denaturing gradient gel electrophoresis (DGGE), real-time PCR, and 16S rRNA gene pyrosequencing. Bacterial diversity assessed by DGGE and/or pyrosequencing was increased by inulin in all three gut locations and by the synbiotic in the caecum and colon. In contrast, the probiotic did only affect the microbiota diversity in the ileum. Shifts in the DGGE microbiota profiles of the caecum and colon were detected for the pro- and synbiotic fed animals, whereas inulin profiles were more similar to the ones of the control. 16S rRNA gene pyrosequencing revealed that all three additives could reduce Escherichia species in each gut location, indicating a potential beneficial effect on the gut microbiota. An increase of relative abundance of Clostridiaceae in the large intestine was found in the inulin group and of Enterococcaceae in the ileum of probiotic fed pigs. Furthermore, real-time PCR results showed that the probiotic and synbiotic increased bifidobacterial numbers in the ileum, which was supported by sequencing results. The probiotic and inulin, to different extents, changed the diversity, relative abundance of phylotypes, and community profiles of the porcine microbiota. However, alterations of the bacterial community were not uniformly between gut locations, demonstrating that functionality of feed additives is site specific. Therefore, gut sampling from various locations is crucial when investigations aim to identify the composition of a healthy gut microbiota after its manipulation through feed additives.

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Identification and Removal of Potential Contaminants in 16S rRNA Gene Sequence Datasets from Low Microbial Biomass Samples: An Example from the Mosquito Gut

10.21203/rs.3.rs-45329/v1 ◽

2020 ◽

Author(s):

Sebastián Diaz ◽

Juan Sebastián Escobar ◽

Frank William Avila

Keyword(s):

Microbial Biomass ◽

16S Rrna ◽

Gut Microbiota ◽

Relative Abundance ◽

Vector Competence ◽

Negative Control ◽

Rrna Gene ◽

Physiological Processes ◽

Physiological Relevance ◽

The Impact

Abstract Background: The bacterial gut microbiota of the female mosquito influences numerous physiological processes, including vector competence. As a low-microbial-biomass ecosystem, mosquito gut tissue is prone to contamination from the laboratory environment and from reagents commonly used to dissect and/or isolate DNA from gut tissue. In this report, we analyze five 16S rRNA datasets, including new data obtained by us, to gain insight into the impact of potential contaminating sequences on the composition, diversity, and structure of the mosquito gut microbial community. Results: We present a clustering-free approach that, based on the relative abundance of amplicon sequence variants (ASVs) in gut and negative control samples , allowed for the identification of candidate contaminating sequences. Some of these sequences belong to bacterial taxa previously identified as common contaminants in metagenomic studies; they have also been identified as part of the mosquito core gut microbiota, with putative physiological relevance for the host. By using different relative abundance cutoffs, we show that contaminating sequences have a significant impact on gut microbiota diversity and structure.Conclusions: The approach presented here allows the identification and removal of purported contaminating sequences in datasets obtained from low-microbial biomass samples. While it was exemplified with the analysis of gut microbiota from mosquitos, it can easily extend to other datasets dealing with similar technical artifacts.

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Metformin Exerts Anti-inflammatory and Mucus Barrier Protective Effects by Enriching Akkermansia muciniphila in Mice With Ulcerative Colitis

Frontiers in Pharmacology ◽

10.3389/fphar.2021.726707 ◽

2021 ◽

Vol 12 ◽

Author(s):

Haoran Ke ◽

Fang Li ◽

Wenlin Deng ◽

Zitong Li ◽

Siqi Wang ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiota ◽

Treated Group ◽

Protective Effects ◽

Microbiota Composition ◽

16S Rrna Analysis ◽

Akkermansia Muciniphila ◽

Anti Inflammatory ◽

Mucus Barrier ◽

Gut Microbiota Composition

The present study aimed to determine if metformin exerts anti-inflammatory and mucus-protective effects via the gut microbiota. Metformin has extensive benefits including anti-inflammatory effects. Previous studies showed that metformin changed the gut microbiota composition and increases the number of goblet cells. Intestinal dysbiosis and goblet cell depletion are important features of ulcerative colitis (UC). The underlying mechanism and whether metformin can improve the mucus barrier in UC remain unclear. Metformin (400 mg/kg/day) was administered to mice with dextran sulfate sodium (DSS)-induced UC for 2 wk to investigate the effects of metformin on the intestinal mucus barrier. The gut microbiota was depleted, using antibiotics, to explore its role in the mucus-protecting effects of metformin. Akkermansia muciniphila (A. muciniphila), which was enriched in metformin-treated mice, was administered to mice to investigate the effects of the bacteria on UC and the mucus barrier. Metformin attenuated DSS-induced UC in mice, as evidenced by the alleviation of diarrhea, hematochezia, and the decrease in body weight. The expression of mucin2, a prominent mucus barrier protein, was increased in the metformin-treated group compared to the DSS-treated group. Furthermore, fecal 16S rRNA analysis showed that metformin treatment changed the gut microbiota composition by increasing the relative abundance of Lactobacillus and Akkermansia species while decreasing Erysipelatoclostridium at the genus level. Antibiotic treatment partly abolished the anti-inflammatory and mucus-protecting effects of metformin. Administration of A. muciniphila alleviated the colonic inflammation and mucus barrier disruption. Metformin alleviated DSS-induced UC in mice and protected against cell damage via affecting the gut microbiota, thereby providing a new mechanism for the therapeutic effect of metformin in patients with UC. This study also provides evidence that A. muciniphila as a probiotic has potential benefits for UC.

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Membership and Behavior of Ultra-Low-Diversity Pathogen Communities Present in the Gut of Humans during Prolonged Critical Illness

mBio ◽

10.1128/mbio.01361-14 ◽

2014 ◽

Vol 5 (5) ◽

Cited By ~ 146

Author(s):

Alexander Zaborin ◽

Daniel Smith ◽

Kevin Garfield ◽

John Quensen ◽

Baddr Shakhsheer ◽

...

Keyword(s):

Critical Illness ◽

16S Rrna ◽

Gut Microbiota ◽

Multidrug Resistant ◽

Nutrient Deprivation ◽

Local Conditions ◽

16S Rrna Analysis ◽

Prolonged Stay ◽

Content Type ◽

Low Diversity

ABSTRACT We analyzed the 16S rRNA amplicon composition in fecal samples of selected patients during their prolonged stay in an intensive care unit (ICU) and observed the emergence of ultra-low-diversity communities (1 to 4 bacterial taxa) in 30% of the patients. Bacteria associated with the genera Enterococcus and Staphylococcus and the family Enterobacteriaceae comprised the majority of these communities. The composition of cultured species from stool samples correlated to the 16S rRNA analysis and additionally revealed the emergence of Candida albicans and Candida glabrata in ~75% of cases. Four of 14 ICU patients harbored 2-member pathogen communities consisting of one Candida taxon and one bacterial taxon. Bacterial members displayed a high degree of resistance to multiple antibiotics. The virulence potential of the 2-member communities was examined in C. elegans during nutrient deprivation and exposure to opioids in order to mimic local conditions in the gut during critical illness. Under conditions of nutrient deprivation, the bacterial members attenuated the virulence of fungal members, leading to a “commensal lifestyle.” However, exposure to opioids led to a breakdown in this commensalism in 2 of the ultra-low-diversity communities. Application of a novel antivirulence agent (phosphate-polyethylene glycol [Pi-PEG]) that creates local phosphate abundance prevented opioid-induced virulence among these pathogen communities, thus rescuing the commensal lifestyle. To conclude, the gut microflora in critically ill patients can consist of ultra-low-diversity communities of multidrug-resistant pathogenic microbes. Local environmental conditions in gut may direct pathogen communities to adapt to either a commensal style or a pathogenic style. IMPORTANCE During critical illness, the normal gut microbiota becomes disrupted in response to host physiologic stress and antibiotic treatment. Here we demonstrate that the community structure of the gut microbiota during prolonged critical illness is dramatically changed such that in many cases only two-member pathogen communities remain. Most of these ultra-low-membership communities display low virulence when grouped together (i.e., a commensal lifestyle); individually, however, they can express highly harmful behaviors (i.e., a pathogenic lifestyle). The commensal lifestyle of the whole community can be shifted to a pathogenic one in response to host factors such as opioids that are released during physiologic stress and critical illness. This shift can be prevented by using compounds such as Pi-PEG15-20 that interrupt bacterial virulence expression. Taking the data together, this report characterizes the plasticity seen with respect to the choice between a commensal lifestyle and a pathogenic lifestyle among ultra-low-diversity pathogen communities that predominate in the gut during critical illness and offers novel strategies for prevention of sepsis.

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Consumption of Goats’ Milk Protects Mice From Carbon Tetrachloride-Induced Acute Hepatic Injury and Improves the Associated Gut Microbiota Imbalance

Frontiers in Immunology ◽

10.3389/fimmu.2018.01034 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 5

Author(s):

Jiachao Zhang ◽

Zhaoxia Wang ◽

Dongxue Huo ◽

Yuyu Shao

Keyword(s):

Carbon Tetrachloride ◽

Gut Microbiota ◽

Hepatic Injury ◽

Acute Hepatic Injury

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Lactobacillus pentosus KCA1 Decreases Vaginal and Gut Microbiota Associated with Bacterial Vaginosis (BV), Down-regulates IL-1 beta in Women of Child-Bearing Age and Modulates Bacterial Genes Related to Metabolic Functions

10.1101/2020.04.02.20040238 ◽

2020 ◽

Author(s):

Kingsley C Anukam ◽

Chinwe E Ejike ◽

Nneka R Agbakoba ◽

Charlotte B Oguejiofor

Keyword(s):

16S Rrna ◽

Gut Microbiota ◽

Bacterial Vaginosis ◽

Relative Abundance ◽

Beta Diversity ◽

Oral Feeding ◽

Lactobacillus Pentosus ◽

Metabolic Functions ◽

Before And After ◽

Bacterial Genes

ABSTRACTIntroductionBacterial vaginosis which affects 14-50% of reproductive-aged women in Nigeria is misdiagnosed and under-reported. Treatment option is antibiotics, which leads to recurrent infections. The objectives of this study are three folds, first to determine effects of oral feeding of Lactobacillus pentosus KCA1 on the vaginal and gut microbiota of women diagnosed with BV; to measure the level of two proinflammatory cytokines IL-1 beta, before and after KCA1 consumption and to determine the relative abundance of bacterial metabolic genes.MethodsSeven women diagnosed with BV by Nugent score (7-10) were recruited to provide vaginal and gut sample before and after 14 days oral intake of 3 grams of Lactobacillus pentosus KCA1. The DNA from the swabs were processed for 16S rRNA metagenomics using Illumina MiSeq platform. The paired-end sequence FASTQ reads were imported into Illumina Basespace pipeline for quality check (QC). In addition, EzBioCloud pipeline was use for alpha and beta diversity estimation using PKSSU4.0 version and open reference UCLUST_MC2 for OTUs picking at 97% cut-off. Blood samples were analyzed using ELISA technique. PICRUSt was used to predict the metabolic functions from the 16S rRNA gene dataset.ResultsOn average, there was no significant difference at p=0.05 in the alpha indices typified by Shannon index. The beta diversity showed different clustering positions with PCoA. However, at individual taxonomic categories, there was a significant decrease in the relative abundance of some genera associated with bacterial vaginosis after KCA1 feeding with a corresponding increase of Lactobacillus genera. Bacterial genes related to defence systems were up-regulated in the vagina. There was a 2-fold down-regulation of IL-1 beta after consumption of KCA1.ConclusionOur findings suggest that Lactobacillus pentosus KCA1 taken orally, lowers pro-inflammatory cytokine, IL-1 beta and decreases the relative abundance of BV-associated bacteria.

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