Colorectal Cancer Stage-Specific Fecal Bacterial Community Fingerprinting of the Taiwanese Population and Underpinning of Potential Taxonomic Biomarkers

Despite advances in the characterization of colorectal cancer (CRC), it still faces a poor prognosis. There is growing evidence that gut microbiota and their metabolites potentially contribute to the development of CRC. Thus, microbial dysbiosis and their metabolites associated with CRC, based on stool samples, may be used to advantage to provide an excellent opportunity to find possible biomarkers for the screening, early detection, prevention, and treatment of CRC. Using 16S rRNA amplicon sequencing coupled with statistical analysis, this study analyzed the cause–effect shift of the microbial taxa and their metabolites that was associated with the fecal gut microbiota of 17 healthy controls, 21 polyps patients, and 21 cancer patients. The microbial taxonomic shift analysis revealed striking differences among the healthy control, polyps and cancer groups. At the phylum level, Synergistetes was reduced significantly in the polyps group compared to the healthy control and cancer group. Additionally, at the genus level and in association with the cancer group, a total of 12 genera were highly enriched in abundance. In contrast, only Oscillosprira was significantly higher in abundance in the healthy control group. Comparisons of the polyps and cancer groups showed a total of 18 significantly enriched genera. Among them, 78% of the genera associated with the cancer group were in higher abundance, whereas the remaining genera showed a higher abundance in the polyps group. Additionally, the comparison of healthy control and polyp groups showed six significantly abundant genera. More than 66% of these genera showed a reduced abundance in the polyps group than in healthy controls, whereas the remaining genera were highly abundant in the polyps group. Based on tumor presence and absence, the abundance of Olsenella and Lactobacillus at the genus level was significantly reduced in the patient group compared to healthy controls. The significant microbial function prediction revealed an increase in the abundance of metabolites in the polyps and cancer groups compared to healthy controls. A correlation analysis revealed a higher contribution of Dorea in the predicted functions. This study showed dysbiosis of gut microbiota at the taxonomic level and their metabolic functions among healthy subjects and in two stages of colorectal cancer, including adenoma and adenocarcinoma, which might serve as potential biomarkers for the early diagnosis and treatment of CRC.

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Study of the Relationship between Microbiome and Colorectal Cancer Susceptibility Using 16SrRNA Sequencing

BioMed Research International ◽

10.1155/2020/7828392 ◽

2020 ◽

Vol 2020 ◽

pp. 1-17 ◽

Cited By ~ 6

Author(s):

Wanxin Liu ◽

Ren Zhang ◽

Rong Shu ◽

Jinjing Yu ◽

Huan Li ◽

...

Keyword(s):

Colorectal Cancer ◽

Gut Microbiota ◽

Cancer Susceptibility ◽

Precancerous Lesions ◽

Bacterial Community Composition ◽

Intestinal Flora ◽

Control Group ◽

Healthy Controls ◽

Healthy Individuals

A lot of previous studies have recently reported that the gut microbiota influences the development of colorectal cancer (CRC) in Western countries, but the role of the gut microbiota in Chinese population must be investigated fully. The goal of this study was to determine the role of the gut microbiome in the initiation and development of CRC. We collected fecal samples of 206 Chinese individuals: 59 with polyp (group P), 54 with adenoma (group A), 51 with colorectal cancer (group CC), and 42 healthy controls (group HC).16S ribosomal RNA (rRNA) was used to compare the microbiota community structures among healthy controls, patients with polyp, and those with adenoma or colorectal cancer. Our study proved that intestinal flora, as a specific indicator, showed significant differences in its diversity and composition. Sobs, Chao, and Ace indexes of group CC were significantly lower than those of the healthy control group (CC group: Sobs, Chao, and Ace indexes were 217.3 ± 69, 4265.1 ± 80.7, and 268.6 ± 78.1, respectively; HC group: Sobs, Chao, and Ace indexes were 228.8 ± 44.4, 272.9 ± 58.6, and 271.9 ± 57.2, respectively). When compared with the healthy individuals, the species richness and diversity of intestinal flora in patients with colorectal cancer were significantly reduced: PCA and PCoA both revealed that a significant separation in bacterial community composition between the CC group and HC group (with PCA using the first two principal component scores of PC1 14.73% and PC2 10.34% of the explained variance, respectively; PCoA : PC1 = 14%, PC2 = 9%, PC3 = 6%). Wilcox tests was used to analyze differences between the two groups, it reveals that Firmicutes (P=0.000356), Fusobacteria (P=0.000001), Proteobacteria (P=0.000796), Spirochaetes (P=0.013421), Synergistetes (P=0.005642) were phyla with significantly different distributions between cases and controls. The proportion of microorganism composition is varying at different stages of colon cancer development: Bacteroidetes (52.14%) and Firmicutes (35.88%) were enriched in the healthy individuals; on the phylum level, the abundance of Bacteroidetes (52.14%-53.92%-52.46%–47.06%) and Firmicutes (35.88%-29.73%-24.27%–25.36%) is decreasing with the development of health-polyp-adenomas-CRC, and the abundance of Proteobacteria (9.33%-12.31%-16.51%–22.37%) is increasing. PCA and PCOA analysis showed there was no significant (P<0.05) difference in species similarity between precancerous and carcinogenic states. However, the composition of the microflora in patients with precancerous lesions (including patients with adenoma and polyp) was proved to have no significant disparity (P<0.05). Our study provides insights into new angles to dig out potential biomarkers in diagnosis and treatment of colorectal cancer and to provide scientific advice for a healthy lifestyle for the sake of gut microbiota.

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The Effect of Lactobacillus plantarum BW2013 on The Gut Microbiota in Mice Analyzed by 16S rRNA Amplicon Sequencing

Polish Journal of Microbiology ◽

10.33073/pjm-2021-022 ◽

2021 ◽

Vol 70 (2) ◽

pp. 235-243

Author(s):

TONG TONG ◽

XIAOHUI NIU ◽

QIAN LI ◽

YUXI LING ◽

ZUMING LI ◽

...

Keyword(s):

16S Rrna ◽

Gut Microbiota ◽

Dose Group ◽

Low Dose ◽

Amplicon Sequencing ◽

Control Group ◽

High Dose ◽

Treatment Groups ◽

16S Rrna Amplicon Sequencing ◽

Medium Dose

Lactobacillus plantarum BW2013 was isolated from the fermented Chinese cabbage. This study aimed to test the effect of this strain on the gut microbiota in BALB/c mice by 16S rRNA amplicon sequencing. The mice were randomly allocated to the control group and three treatment groups of L. plantarum BW2013 (a low-dose group of 108 CFU/ml, a medium-dose group of 109 CFU/ml, and a high-dose group of 1010 CFU/ml). The weight of mice was recorded once a week, and the fecal samples were collected for 16S rRNA amplicon sequencing after 28 days of continuous treatment. Compared with the control group, the body weight gain in the treatment groups was not significant. The 16S rRNA amplicon sequencing analysis showed that both the Chao1 and ACE indexes increased slightly in the medium-dose group compared to the control group, but the difference was not significant. Based on PCoA results, there was no significant difference in β diversity between the treatment groups. Compared to the control group, the abundance of Bacteroidetes increased in the low-dose group. The abundance of Firmicutes increased in the medium-dose group. At the genus level, the abundance of Alloprevotella increased in the low-dose group compared to the control group. The increased abundance of Ruminococcaceae and decreased abundance of Candidatus_Saccharimonas was observed in the medium-dose group. Additionally, the abundance of Bacteroides increased, and Alistipes and Candidatus_Saccharimonas decreased in the high-dose group. These results indicated that L. plantarum BW2013 could ameliorate gut microbiota composition, but its effects vary with the dose.

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Korean Traditional Medicine (Jakyakgamcho-tang) Ameliorates Colitis by Regulating Gut Microbiota

Metabolites ◽

10.3390/metabo9100226 ◽

2019 ◽

Vol 9 (10) ◽

pp. 226 ◽

Cited By ~ 1

Author(s):

Seung-Ho Seo ◽

Tatsuya Unno ◽

Seong-Eun Park ◽

Eun-Ju Kim ◽

Yu-Mi Lee ◽

...

Keyword(s):

Gut Microbiota ◽

Amplicon Sequencing ◽

Control Group ◽

Scaling Analysis ◽

Aminosalicylic Acid ◽

Operational Taxonomic Units ◽

16S Rrna Amplicon Sequencing ◽

Cytokine Levels ◽

Korean Traditional Medicine ◽

Gut Microbial Community

The objective of this study was to examine the anti-colitis activity of Jakyakgamcho-tang (JGT) in dextran sulfate sodium (DSS)-induced colitis and explore changes of the gut microbial community using 16S rRNA amplicon sequencing and metabolomics approaches. It was found that treatment with JGT or 5-aminosalicylic acid (5-ASA) alleviated the severity of colitis symptoms by suppressing inflammatory cytokine levels of IL-6, IL-12, and IFN-γ. The non-metric multidimensional scaling analysis of gut microbiome revealed that JGT groups were clearly separated from the DSS group, suggesting that JGT administration altered gut microbiota. The operational taxonomic units (OTUs) that were decreased by DSS but increased by JGT include Akkermansia and Allobaculum. On the other hand, OTUs that were increased by DSS but decreased by 5-ASA or JGT treatments include Bacteroidales S24-7, Ruminococcaceae, and Rikenellaceae, and the genera Bacteroides, Parabacteroides, Oscillospira, and Coprobacillus. After JGT administration, the metabolites, including most amino acids and lactic acid that were altered by colitis induction, became similar to those of the control group. This study demonstrates that JGT might have potential to effectively treat colitis by restoring dysbiosis of gut microbiota and host metabolites.

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Gut Microbiota Modulation by Dietary Barley Malt Melanoidins

Nutrients ◽

10.3390/nu12010241 ◽

2020 ◽

Vol 12 (1) ◽

pp. 241 ◽

Cited By ~ 1

Author(s):

Nesreen Aljahdali ◽

Pascale Gadonna-Widehem ◽

Pauline M. Anton ◽

Franck Carbonero

Keyword(s):

Fatty Acids ◽

Gut Microbiota ◽

Amplicon Sequencing ◽

Short Chain Fatty Acids ◽

Control Group ◽

Maillard Reaction Products ◽

Reaction Products ◽

Barley Malt ◽

16S Rrna Amplicon Sequencing ◽

The Impact

Melanoidins are the final Maillard reaction products (protein–carbohydrate complexes) produced in food by prolonged and intense heating. We assessed the impact of the consumption of melanoidins from barley malts on gut microbiota. Seventy-five mice were assigned into five groups, where the control group consumed a non-melanoidin malt diet, and other groups received melanoidin-rich malts in increments of 25% up to 100% melanoidin malts. Feces were sampled at days 0, 1, 2, 3, 7, 14, and 21 and the microbiota was determined using V4 bacterial 16S rRNA amplicon sequencing and short-chain fatty acids (SCFA) by gas chromatography. Increased melanoidins was found to result in significantly divergent gut microbiota profiles and supported sustained SCFA production. The relative abundance of Dorea, Oscillibacter, and Alisitpes were decreased, while Lactobacillus, Parasutterella, Akkermansia, Bifidobacterium, and Barnesiella increased. Bifidobacterium spp. and Akkermansia spp. were significantly increased in mice consuming the highest melanoidin amounts, suggesting remarkable prebiotic potential.

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Evaluation of L-fucose and Sialic Acid Levels in Patients With Colorectal Cancer and Control Subject

Research in Molecular Medicine ◽

10.32598/rmm.8.3.609.7 ◽

2020 ◽

Vol 8 (3) ◽

pp. 147-152

Author(s):

Roya Abbasinatajomrani ◽

◽

Durdi Qujeq ◽

Vahid Hosseini ◽

Reza Hajihosseini ◽

...

Keyword(s):

Colorectal Cancer ◽

Sialic Acid ◽

Serum Concentration ◽

Early Stage ◽

Control Group ◽

Healthy Controls ◽

Healthy Control ◽

The Mean ◽

And Control ◽

Potential Cancer

Background: Currently, glycans, which are known as functional molecules in the biological system, are being under study as potential cancer markers. This study aimed to determine the level of serum L-fucose and sialic acid as the biomarkers in patients with colorectal cancer (CRC). Materials and Methods: The patients with CRC (n=40, 20 men and 20 women) participated in the present study. The spectrophotometric method was used to measure the levels of L-fucose and sialic acid in the serum of the patients. SPSS (version 21) was used to analyze the obtained data. The results were expressed as mean ± SD. Results: The mean ± SD L-fucose level in patients with CRC was 27.46 ± 4.8 ng/mL, which was more than this level in the healthy control group (18.64±3.1 ng/mL). Also, the mean ± SD serum concentration of sialic acid in patients with CRC was 2.1 ± 0.41 ng/mL, which was more than the mean ± SD sialic acid level of 1.23±0.21 ng/mL in the healthy controls. Conclusion: Serum concentration of L-fucose and sialic acid increased significantly (P < 0.05) in patients with CRC compared with the healthy controls. We believe that determining serum L-fucose and sialic acid levels could be useful for the detection of CRC patients in the early stage.

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Characterization of the Fecal Microbiota in Gastrointestinal Cancer Patients and Healthy Controls

10.21203/rs.3.rs-37119/v1 ◽

2020 ◽

Author(s):

Ningning Li ◽

Chunmei Bai ◽

Yuanzhi Guan ◽

Lin Zhao ◽

Yuping Ge ◽

...

Keyword(s):

Colorectal Cancer ◽

Gastric Cancer ◽

Gut Microbiota ◽

Cancer Patients ◽

Gastrointestinal Cancer ◽

Fecal Microbiota ◽

Gastrointestinal Tumors ◽

Control Group ◽

Fecal Bacteria ◽

Healthy Controls

Abstract Background The incidence and mortality of gastrointestinal tumors are high in China. Some studies suggested that the gut microbiota is also related to the occurrence and development of tumors. At present, there are no prospective studies based on the correlation between gastrointestinal tumors and gut microbiota in the Chinese population. The objective of this report is to characterize the fecal microbiota in patients with esophageal cancer, gastric cancer, and colorectal cancer and healthy controls. Methods Patients with locally advanced or metastatic esophageal, gastric, and colorectal cancer were enrolled, and healthy people were included as controls. 16S rRNA sequencing was used to analyze the characteristics of fecal microbiota. PICRUSt software was used for functional prediction.Results Significant differences in the composition and abundance of fecal microbiota were identified between gastrointestinal cancer patients and healthy controls. The abundance of F. prausnitzii, C. clostridioforme, and B. adolescents in three different tumor groups was all significantly lower than in the control group (P<0.05). The abundance of R. gnavus, B. obeum, and R. faecis in the gastric and colorectal cancer groups was significantly lower than in the control group (P<0.05). The abundance of Dorea in the gastric cancer group was significantly lower than in the control group (P<0.05). B. fragilis, P. corpi, and E. coli were overabundant in the different tumor groups compared with the control (P<0.05). There were significant differences in functional metabolism and cell biological function between the tumor and control groups (P<0.05). The feces of cancer patients with more advanced staging had higher abundance of Prevotella and fewer Clostridium. Conclusions Patients with esophageal or gastric cancer had similar features of fecal bacteria as those with colorectal cancer. The metabolic function of fecal bacteria in the gastrointestinal cancer patients and the healthy controls were different.

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Gut Microbiome and Metabolome Profiles Associated with High-Fat Diet in Mice

Metabolites ◽

10.3390/metabo11080482 ◽

2021 ◽

Vol 11 (8) ◽

pp. 482

Author(s):

Jae-Kwon Jo ◽

Seung-Ho Seo ◽

Seong-Eun Park ◽

Hyun-Woo Kim ◽

Eun-Ju Kim ◽

...

Keyword(s):

Gut Microbiota ◽

Relative Abundance ◽

High Fat Diet ◽

Amplicon Sequencing ◽

Gas Chromatography Mass Spectrometry ◽

Control Group ◽

Rrna Gene ◽

High Fat ◽

Underlying Mechanisms ◽

Insight Into

Obesity can be caused by microbes producing metabolites; it is thus important to determine the correlation between gut microbes and metabolites. This study aimed to identify gut microbiota-metabolomic signatures that change with a high-fat diet and understand the underlying mechanisms. To investigate the profiles of the gut microbiota and metabolites that changed after a 60% fat diet for 8 weeks, 16S rRNA gene amplicon sequencing and gas chromatography-mass spectrometry (GC-MS)-based metabolomic analyses were performed. Mice belonging to the HFD group showed a significant decrease in the relative abundance of Bacteroidetes but an increase in the relative abundance of Firmicutes compared to the control group. The relative abundance of Firmicutes, such as Lactococcus, Blautia, Lachnoclostridium, Oscillibacter, Ruminiclostridium, Harryflintia, Lactobacillus, Oscillospira, and Erysipelatoclostridium, was significantly higher in the HFD group than in the control group. The increased relative abundance of Firmicutes in the HFD group was positively correlated with fecal ribose, hypoxanthine, fructose, glycolic acid, ornithine, serum inositol, tyrosine, and glycine. Metabolic pathways affected by a high fat diet on serum were involved in aminoacyl-tRNA biosynthesis, glycine, serine and threonine metabolism, cysteine and methionine metabolism, glyoxylate and dicarboxylate metabolism, and phenylalanine, tyrosine, and trypto-phan biosynthesis. This study provides insight into the dysbiosis of gut microbiota and metabolites altered by HFD and may help to understand the mechanisms underlying obesity mediated by gut microbiota.

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Reversion of Gut Microbiota during the Recovery Phase in Patients with Asymptomatic or Mild COVID-19: Longitudinal Study

Microorganisms ◽

10.3390/microorganisms9061237 ◽

2021 ◽

Vol 9 (6) ◽

pp. 1237

Author(s):

Han-Na Kim ◽

Eun-Jeong Joo ◽

Chil-Woo Lee ◽

Kwang-Sung Ahn ◽

Hyung-Lae Kim ◽

...

Keyword(s):

Gut Microbiota ◽

Gastrointestinal Symptoms ◽

Amplicon Sequencing ◽

Recovery Phase ◽

Fecal Samples ◽

Intestinal Microbes ◽

Gut Dysbiosis ◽

16S Rrna Amplicon Sequencing ◽

Microbiome Data ◽

Negative Conversion

Patients with COVID-19 have been reported to experience gastrointestinal symptoms as well as respiratory symptoms, but the effects of COVID-19 on the gut microbiota are poorly understood. We explored gut microbiome profiles associated with the respiratory infection of SARS-CoV-2 during the recovery phase in patients with asymptomatic or mild COVID-19. A longitudinal analysis was performed using the same patients to determine whether the gut microbiota changed after recovery from COVID-19. We applied 16S rRNA amplicon sequencing to analyze two paired fecal samples from 12 patients with asymptomatic or mild COVID-19. Fecal samples were selected at two time points: during SARS-CoV-2 infection (infected state) and after negative conversion of the viral RNA (recovered state). We also compared the microbiome data with those from 36 healthy controls. Microbial evenness of the recovered state was significantly increased compared with the infected state. SARS-CoV-2 infection induced the depletion of Bacteroidetes, while an abundance was observed with a tendency to rapidly reverse in the recovered state. The Firmicutes/Bacteroidetes ratio in the infected state was markedly higher than that in the recovered state. Gut dysbiosis was observed after infection even in patients with asymptomatic or mild COVID-19, while the composition of the gut microbiota was recovered after negative conversion of SARS-CoV-2 RNA. Modifying intestinal microbes in response to COVID-19 might be a useful therapeutic alternative.

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Improvement of Gut Diversity and Composition After Direct-Acting Antivirals in Hepatitis C Virus–Infected Patients With or Without Human Immunodeficiency Virus Coinfection

The Journal of Infectious Diseases ◽

10.1093/infdis/jiab094 ◽

2021 ◽

Author(s):

Natthaya Chuaypen ◽

Thananya Jinato ◽

Anchalee Avihingsanon ◽

Sakkarin Chirapongsathorn ◽

Supapon Cheevadhanarak ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Gut Microbiota ◽

Alpha Diversity ◽

Healthy Controls ◽

Direct Acting Antivirals ◽

Microbial Dysbiosis ◽

Immunodeficiency Virus ◽

Direct Acting

Abstract Background The influence of direct-acting antivirals (DAAs) on the composition of gut microbiota in hepatitis C virus (HCV)–infected patients with or without human immunodeficiency virus (HIV) is unclear. Methods We enrolled 62 patients with HCV monoinfection and 24 patients with HCV/HIV coinfection receiving elbasvir-grazoprevir from a clinical trial. Fecal specimens collected before treatment and 12 weeks after treatment were analyzed using amplicon-based 16S ribosomal RNA sequencing. Results Sustained virological response rates in the monoinfection and coinfection groups were similar (98.4% vs 95.8%). Pretreatment bacterial communities in the patient groups were less diverse and distinct from those of healthy controls. Compared with HCV-monoinfected patients, HCV/HIV-coinfected individuals showed comparable microbial alpha diversity but decreased Firmicutes-Bacteroidetes ratios. The improvement of microbial dysbiosis was observed in responders achieving sustained virological response across fibrosis stages but was not found in nonresponders. Responders with a low degree of fibrosis exhibited a recovery in alpha diversity to levels comparable to those in healthy controls. Reciprocal alterations of increased beneficial bacteria and reduced pathogenic bacteria were also observed in responders. Conclusions This study indicates a short-term effect of direct-acting antivirals in restoration of microbial dysbiosis. The favorable changes in gut microbiota profiles after viral eradication might contribute toward the reduction of HCV-related complications among infected individuals.

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Association between circulating leptin levels and multiple sclerosis: a systematic review and meta-analysis

Postgraduate Medical Journal ◽

10.1136/postgradmedj-2017-135397 ◽

2018 ◽

Vol 94 (1111) ◽

pp. 278-283 ◽

Cited By ~ 3

Author(s):

Xue-Feng Xie ◽

Xiao-Hui Huang ◽

Ai-Zong Shen ◽

Jun Li ◽

Ye-Huan Sun

Keyword(s):

Multiple Sclerosis ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Control Group ◽

Sample Type ◽

Healthy Controls ◽

Eligibility Criteria ◽

Effect Model ◽

Healthy Control

AimLeptin, synthesised by adipocytes, has been identified as a hormone that can influence inflammatory activity. Several studies have investigated leptin levels in patients with multiple sclerosis (MS), but the results are not consistent. This study aims to derive a more precise evaluation on the relationship between circulating leptin levels and MS.DesignA comprehensive literature searched up to July 2017 was conducted to evaluate the association of circulating leptin levels and MS. The random-effect model was applied to calculate pooled standardised mean difference (SMD) and its 95% CI.Main outcome measuresCirculating leptin levels of patients with MS and healthy controls.ResultsOf 2155 studies identified, 33 met eligibility criteria and 9 studies with 645 patients with MS and 586 controls were finally included in the meta-analysis. Meta-analysis revealed that, compared with the healthy control group, the MS group had significantly higher plasma/serum leptin levels, with the SMD of 0.70% and 95% CI (0.24 to 1.15). Subgroup analyses suggested that the leptin levels of patients with MS were associated with region, age, study sample size, measurement type, gender and blood sample type.ConclusionOverall, our study suggests that patients with MS have a significantly higher leptin level than in healthy controls. Further mechanism studies and longitudinal large cohort studies are still needed to further reveal the role of leptin in the pathogenesis of MS.

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