Skip to main content
Top
Published in: BMC Gastroenterology 1/2017

Open Access 01-12-2017 | Research article

Faecal bacterial microbiota in patients with cirrhosis and the effect of lactulose administration

Authors: Aditya Narayan Sarangi, Amit Goel, Ankur Singh, Avani Sasi, Rakesh Aggarwal

Published in: BMC Gastroenterology | Issue 1/2017

Login to get access

Abstract

Background

Gut microbiota may be altered in patients with cirrhosis, and may further change after administration of lactulose. We studied the composition of gut microbiota in patients with cirrhosis and assessed the effect on it of lactulose administration.

Methods

Stool specimens were collected from 35 patients with cirrhosis (male 26; median [range] age: 42 [29–65] years) and 18 healthy controls (male 14; 44.5 [24–67] years); 21 patients provided another specimen after lactulose administration for 55 [42–77] days. For each, a DNA library of V3 region of bacterial 16S ribosomal RNA was subjected to paired-end Illumina sequencing. Inter-specimen relationship was studied using principal co-ordinate analysis. Abundances of various bacterial taxa, and indices of alpha and beta diversity were compared, between patients and controls, and between specimens collected before and after lactulose.

Results

Gut microbiota from cirrhosis patients and controls showed differential clustering, and microbiota from patients with cirrhosis had less marked alpha diversity. Abundances of dominant phyla (Bacteroidetes, Firmicutes and Proteobacteria) were similar. However, patients with cirrhosis had lower abundances of five phyla, namely Tenericutes, Cyanobacteria, Spirochaetes, Elusimicrobia and Lentisphaerae, and differences in abundances of several families and genera than in controls. Lactulose administration did not lead to any change in alpha and beta diversities, species richness and abundances of various bacterial taxa in gut microbiota.

Conclusions

Gut microbiota in cirrhosis differ from healthy persons and do not change following lactulose administration. The latter suggests that the effect of lactulose on hepatic encephalopathy may not be related to alteration in gut microbiota.
Appendix
Available only for authorised users
Literature
1.
go back to reference Sekirov I, Russell SL, Antunes LC, Finlay BB. Gut microbiota in health and disease. Physiol Rev. 2010;90:859–904.CrossRefPubMed Sekirov I, Russell SL, Antunes LC, Finlay BB. Gut microbiota in health and disease. Physiol Rev. 2010;90:859–904.CrossRefPubMed
2.
3.
go back to reference Goel A, Gupta M, Aggarwal R. Gut microbiota and liver disease. J Gastroenterol Hepatol. 2014;29:1139–48.CrossRefPubMed Goel A, Gupta M, Aggarwal R. Gut microbiota and liver disease. J Gastroenterol Hepatol. 2014;29:1139–48.CrossRefPubMed
4.
go back to reference Bass NM, Mullen KD, Sanyal A, Poordad F, Neff G, Leevy CB, et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010;362:1071–81.CrossRefPubMed Bass NM, Mullen KD, Sanyal A, Poordad F, Neff G, Leevy CB, et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010;362:1071–81.CrossRefPubMed
5.
go back to reference Saab S, Suraweera D, Au J, Saab E, Alper T, Tong MJ. Probiotics are helpful in hepatic encephalopathy: a meta-analysis of randomized trials. Liver Int. 2016;36:986–93.CrossRefPubMed Saab S, Suraweera D, Au J, Saab E, Alper T, Tong MJ. Probiotics are helpful in hepatic encephalopathy: a meta-analysis of randomized trials. Liver Int. 2016;36:986–93.CrossRefPubMed
6.
go back to reference Chen C, Li L, Wu Z, Chen H, Fu S. Effects of lactitol on intestinal microflora and plasma endotoxin in patients with chronic viral hepatitis. J Inf Secur. 2007;54:98–102. Chen C, Li L, Wu Z, Chen H, Fu S. Effects of lactitol on intestinal microflora and plasma endotoxin in patients with chronic viral hepatitis. J Inf Secur. 2007;54:98–102.
7.
go back to reference Mortensen PB. The effect of oral-administered lactulose on colonic nitrogen metabolism and excretion. Hepatology. 1992;16:1350–6.CrossRefPubMed Mortensen PB. The effect of oral-administered lactulose on colonic nitrogen metabolism and excretion. Hepatology. 1992;16:1350–6.CrossRefPubMed
8.
go back to reference Riggio O, Varriale M, Testore GP, Di Rosa R, Di Rosa E, Merli M, et al. Effect of lactitol and lactulose administration on the fecal flora in cirrhotic patients. J Clin Gastroenterol. 1990;12:433–6.CrossRefPubMed Riggio O, Varriale M, Testore GP, Di Rosa R, Di Rosa E, Merli M, et al. Effect of lactitol and lactulose administration on the fecal flora in cirrhotic patients. J Clin Gastroenterol. 1990;12:433–6.CrossRefPubMed
9.
go back to reference Vince A, Zeegen R, Drinkwater JE, O'Grady F, Dawson AM. The effect of lactulose on the faecal flora of patients with hepatic encephalopathy. J Med Microbiol. 1974;7:163–8.CrossRefPubMed Vince A, Zeegen R, Drinkwater JE, O'Grady F, Dawson AM. The effect of lactulose on the faecal flora of patients with hepatic encephalopathy. J Med Microbiol. 1974;7:163–8.CrossRefPubMed
10.
go back to reference Fraher MH, O'Toole PW, Quigley EM. Techniques used to characterize the gut microbiota: a guide for the clinician. Nat Rev Gastroenterol Hepatol. 2012;9:312–22.CrossRefPubMed Fraher MH, O'Toole PW, Quigley EM. Techniques used to characterize the gut microbiota: a guide for the clinician. Nat Rev Gastroenterol Hepatol. 2012;9:312–22.CrossRefPubMed
11.
go back to reference Bartram AK, Lynch MD, Stearns JC, Moreno-Hagelsieb G, Neufeld JD. Generation of multimillion-sequence 16S rRNA gene libraries from complex microbial communities by assembling paired-end illumina reads. Appl Environ Microbiol. 2011;77:3846–52.CrossRefPubMedPubMedCentral Bartram AK, Lynch MD, Stearns JC, Moreno-Hagelsieb G, Neufeld JD. Generation of multimillion-sequence 16S rRNA gene libraries from complex microbial communities by assembling paired-end illumina reads. Appl Environ Microbiol. 2011;77:3846–52.CrossRefPubMedPubMedCentral
13.
go back to reference Dai M, Thompson RC, Maher C, Contreras-Galindo R, Kaplan MH, Markovitz DM, et al. NGSQC: cross-platform quality analysis pipeline for deep sequencing data. BMC Genomics. 2010;11(Suppl 4):S7.CrossRefPubMedPubMedCentral Dai M, Thompson RC, Maher C, Contreras-Galindo R, Kaplan MH, Markovitz DM, et al. NGSQC: cross-platform quality analysis pipeline for deep sequencing data. BMC Genomics. 2010;11(Suppl 4):S7.CrossRefPubMedPubMedCentral
14.
go back to reference Navas-Molina JA, Peralta-Sanchez JM, Gonzalez A, McMurdie PJ, Vazquez-Baeza Y, Xu Z, et al. Advancing our understanding of the human microbiome using QIIME. Methods Enzymol. 2013;531:371–444.CrossRefPubMedPubMedCentral Navas-Molina JA, Peralta-Sanchez JM, Gonzalez A, McMurdie PJ, Vazquez-Baeza Y, Xu Z, et al. Advancing our understanding of the human microbiome using QIIME. Methods Enzymol. 2013;531:371–444.CrossRefPubMedPubMedCentral
15.
go back to reference Rideout JR, He Y, Navas-Molina JA, Walters WA, Ursell LK, Gibbons SM, et al. Subsampled open-reference clustering creates consistent, comprehensive OTU definitions and scales to billions of sequences. PeerJ. 2014;2:e545.CrossRefPubMedPubMedCentral Rideout JR, He Y, Navas-Molina JA, Walters WA, Ursell LK, Gibbons SM, et al. Subsampled open-reference clustering creates consistent, comprehensive OTU definitions and scales to billions of sequences. PeerJ. 2014;2:e545.CrossRefPubMedPubMedCentral
16.
go back to reference Caporaso JG, Bittinger K, Bushman FD, DeSantis TZ, Andersen GL, Knight R. PyNAST: a flexible tool for aligning sequences to a template alignment. Bioinformatics. 2010;26:266–7.CrossRefPubMed Caporaso JG, Bittinger K, Bushman FD, DeSantis TZ, Andersen GL, Knight R. PyNAST: a flexible tool for aligning sequences to a template alignment. Bioinformatics. 2010;26:266–7.CrossRefPubMed
18.
19.
go back to reference Gotelli NJ, Anne C. Measuring and estimating species richness, species diversity, and biotic similarity from sampling data. In: Levin SA, editor. Encyclopedia of biodiversity. 2nd ed. Waltham, MA: Academic Press; 2013. p. 195–211.CrossRef Gotelli NJ, Anne C. Measuring and estimating species richness, species diversity, and biotic similarity from sampling data. In: Levin SA, editor. Encyclopedia of biodiversity. 2nd ed. Waltham, MA: Academic Press; 2013. p. 195–211.CrossRef
20.
go back to reference Bajaj JS, Heuman DM, Hylemon PB, Sanyal AJ, White MB, Monteith P, et al. Altered profile of human gut microbiome is associated with cirrhosis and its complications. J Hepatol. 2014;60:940–7.CrossRefPubMed Bajaj JS, Heuman DM, Hylemon PB, Sanyal AJ, White MB, Monteith P, et al. Altered profile of human gut microbiome is associated with cirrhosis and its complications. J Hepatol. 2014;60:940–7.CrossRefPubMed
21.
go back to reference Ley RE, Peterson DA, Gordon JI. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell. 2006;124:837–48.CrossRefPubMed Ley RE, Peterson DA, Gordon JI. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell. 2006;124:837–48.CrossRefPubMed
22.
go back to reference Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464:59–65.CrossRefPubMedPubMedCentral Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464:59–65.CrossRefPubMedPubMedCentral
23.
go back to reference Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, et al. A core gut microbiome in obese and lean twins. Nature. 2009;457:480–4.CrossRefPubMed Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, et al. A core gut microbiome in obese and lean twins. Nature. 2009;457:480–4.CrossRefPubMed
24.
go back to reference Qin J, Li Y, Cai Z, Li S, Zhu J, Zhang F, et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature. 2012;490:55–60.CrossRefPubMed Qin J, Li Y, Cai Z, Li S, Zhu J, Zhang F, et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature. 2012;490:55–60.CrossRefPubMed
25.
26.
go back to reference Zhang Z, Zhai H, Geng J, Yu R, Ren H, Fan H, et al. Large-scale survey of gut microbiota associated with MHE via 16S rRNA-based pyrosequencing. Am J Gastroenterol. 2013;108:1601–11.CrossRefPubMed Zhang Z, Zhai H, Geng J, Yu R, Ren H, Fan H, et al. Large-scale survey of gut microbiota associated with MHE via 16S rRNA-based pyrosequencing. Am J Gastroenterol. 2013;108:1601–11.CrossRefPubMed
27.
go back to reference Qin N, Yang F, Li A, Prifti E, Chen Y, Shao L, et al. Alterations of the human gut microbiome in liver cirrhosis. Nature. 2014;513:59–64.CrossRefPubMed Qin N, Yang F, Li A, Prifti E, Chen Y, Shao L, et al. Alterations of the human gut microbiome in liver cirrhosis. Nature. 2014;513:59–64.CrossRefPubMed
28.
go back to reference Manichanh C, Rigottier-Gois L, Bonnaud E, Gloux K, Pelletier E, Frangeul L, et al. Reduced diversity of faecal microbiota in Crohn's disease revealed by a metagenomic approach. Gut. 2006;55:205–11.CrossRefPubMedPubMedCentral Manichanh C, Rigottier-Gois L, Bonnaud E, Gloux K, Pelletier E, Frangeul L, et al. Reduced diversity of faecal microbiota in Crohn's disease revealed by a metagenomic approach. Gut. 2006;55:205–11.CrossRefPubMedPubMedCentral
29.
go back to reference Le Chatelier E, Nielsen T, Qin J, Prifti E, Hildebrand F, Falony G, et al. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013;500:541–6.CrossRefPubMed Le Chatelier E, Nielsen T, Qin J, Prifti E, Hildebrand F, Falony G, et al. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013;500:541–6.CrossRefPubMed
30.
go back to reference Chen Y, Yang F, Lu H, Wang B, Chen Y, Lei D, et al. Characterization of fecal microbial communities in patients with liver cirrhosis. Hepatology. 2011;54:562–72.CrossRefPubMed Chen Y, Yang F, Lu H, Wang B, Chen Y, Lei D, et al. Characterization of fecal microbial communities in patients with liver cirrhosis. Hepatology. 2011;54:562–72.CrossRefPubMed
33.
go back to reference Avery GS, Davies EF, Brogden RN. Lactulose: a review of its therapeutic and pharmacological properties with particular reference to ammonia metabolism and its mode of action of portal systemic encephalopathy. Drugs. 1972;4:7–48.CrossRefPubMed Avery GS, Davies EF, Brogden RN. Lactulose: a review of its therapeutic and pharmacological properties with particular reference to ammonia metabolism and its mode of action of portal systemic encephalopathy. Drugs. 1972;4:7–48.CrossRefPubMed
34.
go back to reference Macgillivray PC, Finlay HV, Binns TB. Use of lactulose to create a preponderance of lactobacilli in the intestine of bottle-fed infants. Scott Med J. 1959;4:182–9.CrossRefPubMed Macgillivray PC, Finlay HV, Binns TB. Use of lactulose to create a preponderance of lactobacilli in the intestine of bottle-fed infants. Scott Med J. 1959;4:182–9.CrossRefPubMed
35.
go back to reference Elkington SG, Floch MH, Conn HO. Lactulose in the treatment of chronic portal-systemic encephalopathy. A double-blind clinical trial. N Engl J Med. 1969;281:408–12.CrossRefPubMed Elkington SG, Floch MH, Conn HO. Lactulose in the treatment of chronic portal-systemic encephalopathy. A double-blind clinical trial. N Engl J Med. 1969;281:408–12.CrossRefPubMed
36.
go back to reference Conn HO, Floch MH. Effects of lactulose and lactobacillus acidophilus on the fecal flora. Am J Clin Nutr. 1970;23:1588–94.PubMed Conn HO, Floch MH. Effects of lactulose and lactobacillus acidophilus on the fecal flora. Am J Clin Nutr. 1970;23:1588–94.PubMed
37.
go back to reference Bircher J, Scollo-Lavizzari G, Hoffmann K, Haemmerli UP. Treatment of chronic porto-systemic encephalopathy with lactulose. Schweiz Med Wochenschr. 1969;99:584.PubMed Bircher J, Scollo-Lavizzari G, Hoffmann K, Haemmerli UP. Treatment of chronic porto-systemic encephalopathy with lactulose. Schweiz Med Wochenschr. 1969;99:584.PubMed
38.
go back to reference Bajaj JS, Ridlon JM, Hylemon PB, Thacker LR, Heuman DM, Smith S, et al. Linkage of gut microbiome with cognition in hepatic encephalopathy. Am J Physiol Gastrointest Liver Physiol. 2012;302:G168–75.CrossRefPubMed Bajaj JS, Ridlon JM, Hylemon PB, Thacker LR, Heuman DM, Smith S, et al. Linkage of gut microbiome with cognition in hepatic encephalopathy. Am J Physiol Gastrointest Liver Physiol. 2012;302:G168–75.CrossRefPubMed
39.
go back to reference Rahimi RS, Singal AG, Cuthbert JA, Rockey DC. Lactulose vs polyethylene glycol 3350--electrolyte solution for treatment of overt hepatic encephalopathy: the HELP randomized clinical trial. JAMA Intern Med. 2014;174:1727–33.CrossRefPubMedPubMedCentral Rahimi RS, Singal AG, Cuthbert JA, Rockey DC. Lactulose vs polyethylene glycol 3350--electrolyte solution for treatment of overt hepatic encephalopathy: the HELP randomized clinical trial. JAMA Intern Med. 2014;174:1727–33.CrossRefPubMedPubMedCentral
40.
go back to reference Bajaj JS, Hylemon PB, Ridlon JM, Heuman DM, Daita K, White MB, et al. Colonic mucosal microbiome differs from stool microbiome in cirrhosis and hepatic encephalopathy and is linked to cognition and inflammation. Am J Physiol Gastrointest Liver Physiol. 2012;303:G675–85.CrossRefPubMedPubMedCentral Bajaj JS, Hylemon PB, Ridlon JM, Heuman DM, Daita K, White MB, et al. Colonic mucosal microbiome differs from stool microbiome in cirrhosis and hepatic encephalopathy and is linked to cognition and inflammation. Am J Physiol Gastrointest Liver Physiol. 2012;303:G675–85.CrossRefPubMedPubMedCentral
41.
go back to reference Xu Z, Knight R. Dietary effects on human gut microbiome diversity. Br J Nutr. 2015;113(Suppl):S1–5.CrossRefPubMed Xu Z, Knight R. Dietary effects on human gut microbiome diversity. Br J Nutr. 2015;113(Suppl):S1–5.CrossRefPubMed
42.
go back to reference Mutlu EA, Gillevet PM, Rangwala H, Sikaroodi M, Naqvi A, Engen PA, et al. Colonic microbiome is altered in alcoholism. Am J Physiol Gastrointest Liver Physiol. 2012;302:G966–78.CrossRefPubMedPubMedCentral Mutlu EA, Gillevet PM, Rangwala H, Sikaroodi M, Naqvi A, Engen PA, et al. Colonic microbiome is altered in alcoholism. Am J Physiol Gastrointest Liver Physiol. 2012;302:G966–78.CrossRefPubMedPubMedCentral
Metadata
Title
Faecal bacterial microbiota in patients with cirrhosis and the effect of lactulose administration
Authors
Aditya Narayan Sarangi
Amit Goel
Ankur Singh
Avani Sasi
Rakesh Aggarwal
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Gastroenterology / Issue 1/2017
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/s12876-017-0683-9

Other articles of this Issue 1/2017

BMC Gastroenterology 1/2017 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.