Saudi Journal of Gastroenterology
Home About us Instructions Submission Subscribe Advertise Contact Login    Print this page  Email this page Small font sizeDefault font sizeIncrease font size 
Users Online: 2342 


 
Table of Contents   
ORIGINAL ARTICLE  
Year : 2018  |  Volume : 24  |  Issue : 1  |  Page : 59-66
Lactobacillus acidophilus and Bifidobacterium longum supernatants upregulate the serotonin transporter expression in intestinal epithelial cells


Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China

Click here for correspondence address and email

Date of Web Publication14-Feb-2018
 

   Abstract 


Background/Aims: Probiotics play a role in relieving irritable bowel syndrome (IBS); however, the underlying mechanism is yet unclear. The aim of the study was to investigate the effects of the supernatants of Lactobacillus acidophilus and Bifidobacterium longum on the expression of serotonin transporter (SERT) messenger ribonucleic acid (mRNA) and protein.
Materials and Methods: HT-29 and Caco-2 cells were treated with different concentrations of L. acidophilus and B. longum supernatants for 12 h and 24 h, respectively. SERT mRNA and proteins levels were detected by real-time polymerase chain reaction (real-time PCR) and Western-blotting.
Results: The mRNA levels of SERT in HT-29 and Caco-2 cells treated with different concentrations of L. acidophilus or B. longum supernatants for 12 h and 24 h, each, were higher than that in the control groups. In addition, the expression of the protein in both cells was also upregulated, which was approximately similar to that of the corresponding mRNA.
Conclusions: L. acidophilus and B. longum supernatants can upregulate SERT mRNA and protein levels in intestinal epithelial cells.

Keywords: Bifidobacterium longum supernatant, intestinal epithelial cells, Lactobacillus acidophilus supernatant, serotonin transporter

How to cite this article:
Cao YN, Feng LJ, Wang BM, Jiang K, Li S, Xu X, Wang WQ, Zhao JW, Wang YM. Lactobacillus acidophilus and Bifidobacterium longum supernatants upregulate the serotonin transporter expression in intestinal epithelial cells. Saudi J Gastroenterol 2018;24:59-66

How to cite this URL:
Cao YN, Feng LJ, Wang BM, Jiang K, Li S, Xu X, Wang WQ, Zhao JW, Wang YM. Lactobacillus acidophilus and Bifidobacterium longum supernatants upregulate the serotonin transporter expression in intestinal epithelial cells. Saudi J Gastroenterol [serial online] 2018 [cited 2019 Nov 12];24:59-66. Available from: http://www.saudijgastro.com/text.asp?2018/24/1/59/225389





   Introduction Top


Irritable bowel syndrome (IBS) is a functional bowel disorder; the abdominal pain or discomfort is associated with defecation and/or a change in bowel habit. According to the Rome IV criteria,[1] IBS may be sub-classified as IBS with predominant constipation (IBS-C), IBS with predominant diarrhea (IBS-D), IBS with mixed bowel habits (IBS-M), and IBS unclassified (IBS-U). The level of severity of IBS is modulated by various factors, such as chronic immunity reactions after intestinal microbiome alteration, visceral hypersensitivity associated with gut-brain pathways, and impaired bowel permeability.[2] As a signal transducer and a neurotransmitter, serotonin (5-hydroxytryptamine, 5-HT) mediates the intercellular signaling transmission in the gut, which occurs maximally in the enterochromaffin cells of the gut. The levels of 5-HT decrease in patients with IBS-C and increase in patients with IBS-D.[3] The inactivation of 5-HT is equally crucial as its release for the maintenance of the dynamic equilibrium. Similar to the number of neurotransmitter sodium symporters or the solute carrier superfamily 6, the serotonin transporter (SERT) plays a unique role in the inactivation of 5-HT by its removal from the interstitial space in the lamina propria into mucosal enterocytes and presynaptic neurons that are responsible for catabolism. Coates et al. first characterized a significantly decreased level of SERT in IBS.[4] However, another conflicting finding showed increased SERT expression in IBS.[5],[6] Despite the lack of consensus on the wide range of roles of potential factors, immunity activation, inflammatory response, gut microbiota, and their relationships have been suggested to regulate the expression of SERT in post-infectious IBS (PI-IBS).[7]

Lactobacillus acidophilus and Bifidobacterium longum are two probiotics that have been used in the clinical treatment of IBS. The previous study demonstrated that Lactobacillus rhamnosus GG (LGG) supernatant could upregulate the SERT messenger ribonucleic acid (mRNA) and protein levels in intestinal epithelial cells and mice intestinal tissues.[8] However, the widely used probiotics for IBS include L. acidophilus and B. longum. Whether the supernatants of these two species could also improve intestinal motility and gastrointestinal sensation by regulating SERT expression is yet to be elucidated. Thus, the present study investigated the effects of the supernatants of L. acidophilus and B. longum on the expression of SERT mRNA and protein.


   Materials and Methods Top


Bacterial culture, L. acidophilus and B. longum supernatants

L. acidophilus (ATCC 4356) and B. longum (ATCC 15707) were obtained from China General Microbiological Culture Collection Center.

L. acidophilus was incubated in lactic acid bacteria culture medium (MRS) broth (Thermo Fisher Oxoid, UK) at 37°C for 24 h, followed by dilution in the MRS broth and incubation to reach the exponential phase with the density of 0.5 at optical density (OD) 600. On the other hand, B. longum was incubated in brain heart infusion (BHI) as described above. The culture suspensions were centrifuged at 5,000 × g for 10 min at 4°C. The supernatant was filter-sterilized through 0.22 μm filters.

Cell culture and cell treatment

HT-29, a human colonic epithelial carcinoma cell line, was grown in Dulbecco's Modified Eagle Medium (DMEM) media supplemented with 10% fetal bovine serum and 1.0% nonessential amino acids at 37°C. Caco-2, a continuous heterogeneous human epithelial colorectal adenocarcinoma cell line, was grown in Minimum Essential Medium (MEM) media supplemented with 20% fetal bovine serum and 1.0% nonessential amino acids at 37°C. The cells were serum starved (0.5%) at 37°C for approximately 24 h before the experiments and then treated with the supernatants of L. acidophilus and B. longum, respectively (supernatant-to-cell media ratios: 1:100, 1:50, and 1:20) for 12 h and 24 h. The control cells were treated with MRS and BHI broth, respectively.

Real-time polymerase chain reaction

The total RNA from HT-29 and Caco-2 cells was extracted using TRIzol reagent® (Life, Hilden, Germany) after the cells were treated with the supernatants of L. acidophilus and B. longum, respectively for 12 h and 24 h. The complementary deoxyribonucleic acid (cDNA) was synthesized with a two-step reverse transcription kit (BioRad Laboratories Inc., Hercules, CA, USA), followed by real-time PCR conducted on an Applied Biosystems (ABI) One plus setup PCR thermocycler using the SYBR Green PCR Master Mix (Roche Applied Science, Mannheim, Germany) in a 96-well plate. The PCR reactions were set up in a volume of 20 μL containing 2 μL cDNA, 10 μL 2 × iQ SYBR ® Green Supermix (Roche Applied Science, Mannheim, Germany), 1 μL each of the forward and reverse primers, and filled the remaining with the RNase-Free Water. The PCR cycle parameters were as follows: initial denaturation at 95°C for 10 min, 40 cycles of 95°C for 10 s and 60°C for 30 s, followed by a dissociation stage for recording the melting curve. The cycle threshold (Ct) values for all genes were obtained, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was measured as an internal control for normalization. Data were analyzed according to the relative expression using the 2-ΔΔCt method. Each sample was analyzed in triplicate, and the mean values were presented. Primers used for the PCR were: SERT forward, 5'-AAT GGG TAC TCA GCA GTT CC-3' and reverse, 5'-CCA CAG CAT AGC CAA TCA C- 3'; GAPDH forward, 5'-CCCTTCATTGACCTCAACTACATGG-3' and reverse, 5'- CATGGTGGTGAAGACGCCAG-3'.

Western blotting

Proteins were extracted from HT-29 and Caco-2 cells after treating with L. acidophilus and B. longum supernatants, respectively for 12 h and 24 h; the concentrations were determined by a Bicinchoninic Acid (BCA) protein assay kit (Beijing Solarbio Science and Technology Co., Ltd., Beijing, China). The remaining supernatant (60 μL) was combined (3:1) with 4 × Sodium dodecyl sulfate-Polyacrylamide gel electrophoresis (SDS-PAGE) loading buffer, and boiled for 10 min. An equivalent of 20 μg protein from each sample was analyzed on a 10% SDS-PAGE and electrophoretically transferred to polyvinylidene difluoride membranes. The membranes were blocked with 5% (w/v) nonfat milk, and SERT protein was detected using rabbit anti-SERT polyclonal antibody (ab181034, 1:500; Abcam, Cambridge, UK). Mouse anti-β-actin (Abcam) monoclonal antibody was used to the reference protein. The membranes were incubated with either horseradish peroxidase-labeled goat anti-rabbit (EarthOx Life Sciences, Millbrae, CA, USA) or goat anti-mouse secondary antibodies (EarthOx Life Sciences). All the antibodies were diluted with 5% (w/v) nonfat milk. The SERT/β-actin ratio was calculated from the films with the Quantity One Analysis Software (Bio-Rad, Hercules, CA, USA), and the results expressed in densitometric units.

Statistical analyses

The statistical analysis was carried out using SPSS 19.0 (SPSS, Chicago, IL, USA). One-way analysis of variance (ANOVA) and posthoc tests (Dunnett's T3 and Dunnett's C) were used to compare the values of RT-PCR. For all analyses, P = 0.05 was defined as statistically significant.


   Results Top


Effects of L. acidophilus supernatant on SERT mRNA and protein expression in HT-29 and Caco-2 cells

The mRNA levels of SERT in HT-29 cells treated with 1:100, 1:50, and 1:20 dilutions of L. acidophilus supernatant for 12 h were 1.80-, 2.24-, and 2.28-fold higher than that in the control group, respectively (P< 0.05, P < 0.05, P < 0.05). On the other hand, the levels after 24 h treatment were 2.04, 2.30, and 2.80-fold higher than that in the control group, respectively (P< 0.05, P < 0.05, P < 0.05). The upregulated of SERT mRNA stimulated by 1:20 dilution of L. acidophilus supernatant for 24 h was significantly higher than that by 1:100 (P< 0.05). Similarly, the protein levels were increased significantly in response to 12 h and 24 h incubation of HT-29 cells at 1:100, 1:50, and 1:20 of L. acidophilus supernatant [Figure 1]: SERT in HT-29 cells treated with L. acidophilus supernatant].
Figure 1: SERT in HT-29 cells treated with L. acidophilus supernatant. The levels of mRNA of 12h (a), 24h (b); the protein of 12h (c and e), 24h (d and f). *: P<0.05, a significant difference

Click here to view


SERT mRNA levels in Caco-2 cells treated with 1:100, 1:50, and 1:20 dilutions of L. acidophilus supernatant for 12 h were 1.20-, 1.22-, and 1.61-fold higher than that in the control group, respectively (P > 0.05, P > 0.05, P < 0.05). SERT mRNA levels in Caco-2 cells treated with 1:100, 1:50, and 1:20 dilutions of L. acidophilus supernatant for 24 h were 1.16-, 1.50-, and 2.13-fold higher than that in the control group, respectively (P > 0.05, P < 0.05, P < 0.05, respectively). The upregulated of SERT mRNA stimulated by 1:20 dilution of L. acidophilus supernatant for 12 h and 24 h was significantly higher than that by 1:100 and 1:50 (P< 0.05, P < 0.05, respectively). The upregulated level of SERT mRNA stimulated by 1:50 of L. acidophilus supernatant for 24 h was also significantly higher than that by 1:100 (P< 0.05). The increase in protein levels in Caco-2 cells in response to 12 h and 24 h incubation in different concentrations of L. acidophilus supernatant were similar to that of SERT mRNA [Figure 2]: SERT in Caco-2 cells treated with L. acidophilus supernatant].
Figure 2: SERT in Caco-2 cells treated with L. acidophilus supernatant. The levels of mRNA of 12h (a), 24h (b); the protein of 12h (c and e), 24h (d and f). *: P<0.05, a significant difference

Click here to view


Effects of B. longum supernatant on SERT mRNA and protein expression in HT-29 and Caco-2 cells

The SERT mRNA levels in HT-29 cells treated with dilutions 1:100, 1:50, and 1:20 of B. longum supernatant for 12 h were 0.96-, 1.90-, and 2.50-fold higher than that in the control group, respectively (P > 0.05, P < 0.05, P < 0.05, respectively). The mRNA levels after 24 h treatment were 2.58-, 2.19-, and 3.21-fold higher than that in the control group, respectively (P< 0.05, P < 0.05, P < 0.05, respectively). The upregulated level of SERT mRNA stimulated by 1:20 concentration of B. longum supernatant for 12 h was significantly higher than that by 1:100 (P< 0.05). Similar to the mRNA levels, the protein levels were significantly increased in response to 12 h and 24 h incubation of HT-29 cells at 1:50 and 1:20 concentrations of B. longum supernatant [Figure 3]: SERT in HT-29 cells treated with B. longum supernatant].
Figure 3: SERT in HT-29 cells treated with B. longum supernatant. The levels of mRNA of 12h (a), 24h (b); the protein of 12h (c and e), 24h (d and f). *: P<0.05, a significant difference

Click here to view


The SERT mRNA levels in Caco-2 cells treated with 1:100, 1:50, and 1:20 dilutions of B. longum supernatant for 12 h were 1.25-, 2.06-, and 1.83-fold higher than that in the control group, respectively (P > 0.05, P < 0.05, P < 0.05, respectively). SERT mRNA levels in Caco-2 cells treated with1:100, 1:50, and 1:20 concentrations of B. longum supernatant for 24 h were 1.84-, 2.23-, and 2.13-fold higher than that in the control group, respectively (P< 0.05, P < 0.05, P < 0.05). The upregulated levels of SERT mRNA stimulated by 1:20 and 1:50 concentrations of B. longum supernatant for 12 h were significantly higher than that by 1:100 (P< 0.05, P < 0.05). The increase in the protein levels in Caco-2 cells in response to 24 h incubation at different concentrations of B. longum supernatant were similar to that of SERT mRNA [Figure 4]: SERT in Caco-2 cells treated with B. longum supernatant].
Figure 4: SERT in Caco-2 cells treated with B. longum supernatant. The levels of mRNA of 12h (a), 24h (b); the protein of 12h (c and e), 24h (d and f). *: P<0.05, a significant difference

Click here to view



   Discussion Top


IBS is a chronic functional bowel disease with a prevalence of 10-15% in the industrialized world.[9] As a multifactorial functional disorder, the pathophysiology of IBS is not completely understood; however, the genetic factors, visceral hypersensitivity, gastrointestinal motility abnormalities, and other factors might be involved in the pathogenesis of IBS.[10],[11]

Probiotics are defined as living microorganisms, which exert beneficial effects on human health upon ingestion. The most commonly administered probiotics belong to genera lactobacillus or bifidobacterium and can be applied alone (monospecies) or in combination with several other species (multispecies). A meta-analysis showed that probiotics improved the pain scores if they contained B. breve, B. longum, or L. acidophilus. Distension scores were improved by probiotics containing B. breve, B. infantis, L. casei, or L. plantarum species.[12] Yoon et al. found that multispecies probiotics (a mixture of B. longum, B. bifidum, B. lactis, L. acidophilus, L. rhamnosus, and Streptococcus thermophiles) are effective in IBS patients that can alter the composition of intestinal microbiota.[13]

L. acidophilus is a Gram-positive bacilli belonging to the genus Lactobacillus and can release lactic acid, acetic acid, and some antibiotics primarily in the small intestine.[14],[15] Bifidobacterium is an anaerobic Gram-positive bacillus isolated from the feces of breast-fed infants by Tissier et al.[16] Bifidobacterium genus of bacteria harbors more than 30 species, of which, nine are present in the human intestinal tract.[17],[18],[19],[20]L. acidophilus and B. longum are used clinically and have been widely used in probiotic research. Current studies have shown that L. acidophilus and B. longum can improve the clinical symptoms in IBS patients; however, the underlying mechanism is not clear. The previous studies have shown that LGG supernatants can upregulate the levels of SERT expression in Caco-2, HT-29, and mouse colon tissues.[8] Moreover, we hypothesize that L. acidophilus and B. longum can regulate the expression level of SERT in intestinal epithelium cells.

In the present study, the expression levels of SERT mRNA and protein were significantly upregulated in HT-29 cells treated with different concentrations of L. acidophilus supernatant at 12 h and 24 h, and was found to be time-dependent. The expression levels of SERT mRNA and protein stimulated by each concentration of L. acidophilus supernatant for 24 h was higher than that for 12 h. However, the L. acidophilus supernatant diluted to 1:100 upregulated the SERT mRNA and protein levels in Caco-2 cells when treated for 12 h and 24 h without statistical significance. Similar to the L. acidophilus supernatant, the B. longum supernatant diluted to 1:50 and 1:20 increased the expression levels of SERT mRNA and protein in HT-29 cells when treated for 12 and 24h. The B. longum supernatant diluted to 1:100 significantly increased the expression levels of SERT mRNA in HT-29 cells when treated for 24 h; however, the expression levels of the protein in HT-29 cells were increased after treatment for 24 h without statistical significance. This phenomenon might be attributed to the fact that in addition to B. longum supernatant, other unknown factors might effect the SERT protein expression. Moreover, the expression levels of SERT mRNA and protein were significantly upregulated in Caco-2 cells treated with different concentrations of B. longum supernatant at 12 h and 24 h similar to that in HT-29 cells.

The supernatant of L. acidophilus and B. longum could up-regulate the expression of SERT mRNA in HT-29 and Caco-2 cells, which is time- and concentration-dependent and the current data were not sufficient in order to demonstrate the statistical differences between the two probiotics. The level of expression of SERT protein in the stimulated groups was not identical to that of the mRNA expression, which may be attributed to various unknown factors regulating the process of translation from mRNA to protein; however, the trend of mRNA and protein expression was similar.

Considering that enteric 5-HT is responsible for the secretion, motility, and perception of the bowel.[4],[21] High 5-HT is commonly associated with depressed SERT mRNA in patients with IBS as compared to healthy controls.[22],[23] The difference in the expression of SERT between IBS patients and healthy controls might suggest that SERT plays an essential role in IBS pathogenesis,[24],[25],[26],[27],[28],[29] and could serve as a novel therapeutic target for IBS. SERT could be regulated by several factors, including gene polymorphisms,[30],[31] microRNAs,[32] immunity, and inflammation,[33] and growth factors.[34],[35],[36] Our study showed that L. acidophilus supernatant and B. longum supernatant could increase the expression of SERT in the intestinal epithelial cells. Based on the results of the current study, we aspire to explore similar macromolecular proteins between different probiotics strains in order to identify the factors that stimulate the upregulation of SERT expression.


   Conclusion Top


In summary, we demonstrate that the supernatants of L. acidophilus and B. longum upregulate the expression SERT in HT-29 and Caco-2 cells. Since the levels of 5-HT are decreased, this may indicate a potential mechanism for the usage of probiotics.

Financial support and sponsorship

This study was supported by a grant from the National Natural Science Foundation of China (No. 81570489).

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Drossman DA, Hasler WL. Rome IV-functional GI disorders: Disorders of gut-brain interaction. Gastroenterology 2016;150:1257-61.  Back to cited text no. 1
[PUBMED]    
2.
Didari T, Mozaffari S, Nikfar S, Abdollahi M. Effectiveness of probiotics in irritable bowel syndrome: Updated systematic review with meta-analysis. World J Gastroenterol 2015;21:3072-84.  Back to cited text no. 2
[PUBMED]    
3.
Bearcroft CP, Perrett D, Farthing MJ. Postprandial plasma 5-hydroxytryptamine in diarrhoea predominant irritable bowel syndrome: A pilot study. Gut 1998;42:42-6.  Back to cited text no. 3
[PUBMED]    
4.
Coates MD, Mahoney CR, Linden DR, Sampson JE, Chen J, Blaszyk H, et al. Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology 2004;126:1657-64.  Back to cited text no. 4
[PUBMED]    
5.
Kerckhoffs AP, Ter Linde JJ, Akkermans LM, Samsom M. Trypsinogen IV, serotonin transporter transcript levels and serotonin content are increased in small intestine of irritable bowel syndrome patients. Neurogastroenterol Motil 2008;20:900-7.  Back to cited text no. 5
    
6.
Wendelbo I, Mazzawi T, El-Salhy M. Increased serotonin transporter immunoreactivity intensity in the ileum of patients with irritable bowel disease. Mol Med Rep 2014;9:180-4.  Back to cited text no. 6
    
7.
Sundin J, Rangel I, Repsilber D, Brummer RJ. Cytokine response after stimulation with key commensal bacteria differ in post-infectious irritable bowel syndrome (PI-IBS) patients compared to healthy controls. PloS One 2015;10:e0134836.  Back to cited text no. 7
    
8.
Wang YM, Ge XZ, Wang WQ, Wang T, Cao HL, Wang BL, et al. Lactobacillus rhamnosus GG supernatant upregulates serotonin transporter expression in intestinal epithelial cells and mice intestinal tissues. Neurogastroenterol Motil 2015;27:1239-48.  Back to cited text no. 8
    
9.
Lovell RM, Ford AC. Global prevalence of and risk factors for irritable bowel syndrome: A meta-analysis. Clin Gastroenterol Hepatol 2012;10:712-21.  Back to cited text no. 9
    
10.
Spiller R, Aziz Q, Creed F, Emmanuel A, Houghton L, Hungin P, et al. Guidelines on the irritable bowel syndrome: Mechanisms and practical management. Gut 2007;56:1770-98.  Back to cited text no. 10
    
11.
Zhong L, Hou X. Pathophysiologic findings of irritable bowel syndrome in china. J Neurogastroenterol Motil 2012;18:19-33.  Back to cited text no. 11
    
12.
Ortiz-Lucas M, Tobias A, Saz P, Sebastián JJ. Effect of probiotic species on irritable bowel syndrome symptoms: A bring up to date meta-analysis. Rev Esp Enferm Dig 2013;105:19-36.  Back to cited text no. 12
    
13.
Yoon JS, Sohn W, Lee OY, Lee SP, Lee KN, Jun DW, et al. Effect of multispecies probiotics on irritable bowel syndrome: A randomized, double-blind, placebo-controlled trial. J Gastroenterol Hepatol 2014;29:52-9.  Back to cited text no. 13
    
14.
Curran HR, Rogers LA, Whittier EO. The distinguishing characteristics of Lactobacillus acidophilus. J Bacteriol 1933;25:595-621.  Back to cited text no. 14
    
15.
Vincent JG, Veomett RC, Riley RF. Antibacterial activity associated with Lactobacillus acidophilus. J Bacteriol 1959;78:477-84.  Back to cited text no. 15
    
16.
Tissier, Compt. rend. Recherches sur la flore intestinale des nourrissons. Soc. de biol 1899; 943.  Back to cited text no. 16
    
17.
von Ah U, Mozzetti V, Lacroix C, Kheadr EE, Fliss I, Meile L. Classification of a moderately oxygen-tolerant isolate from baby faeces as Bifidobacterium thermophilum. BMC Microbiol 2007;7:79.  Back to cited text no. 17
    
18.
Crociani F, Biavati B, Alessandrini A, Chiarini C, Scardovi V. Bifidobacterium inopinatum sp. nov. and Bifidobacterium denticolens sp. nov., two new species isolated from human dental caries. Int J Syst Bacteriol 1996;46:564-71.  Back to cited text no. 18
    
19.
Lauer E. Bifidobacterium gallicum sp. nov. isolated from human feces. Int J Syst Bacteriol 1990;40:100-2.  Back to cited text no. 19
    
20.
Matsuki T, Watanabe K, Tanaka R, Fukuda M, Oyaizu H. Distribution of bifidobacterial species in human intestinal microflora examined with 16S rRNA-gene-targeted species-specific primers. Appl Environ Microbiol 1999;65:4506-12.  Back to cited text no. 20
    
21.
McCartney AL, Wenzhi W, Tannock GW. Molecular analysis of the composition of the bifidobacterial and lactobacillus microflora of humans. Appl Environ Microbiol 1996;62:4608-13.  Back to cited text no. 21
    
22.
Gershon MD, Tack J. The serotonin signaling system: From basic understanding to drug development for functional GI disorders. Gastroenterology 2007;132:397-414.  Back to cited text no. 22
    
23.
Foley S, Garsed K, Singh G, Duroudier NP, Swan C, Hall IP, et al. Impaired uptake of serotonin by platelets from patients with irritable bowel syndrome correlates with duodenal immune activation. Gastroenterology 2011;140:1434-43.  Back to cited text no. 23
    
24.
Wang YM, Chang Y, Chang YY, Cheng J, Li J, Wang T, et al. Serotonin transporter gene promoter region polymorphisms and serotonin transporter expression in the colonic mucosa of irritable bowel syndrome patients. Neurogastroenterol Motil 2012;24:560-5.  Back to cited text no. 24
    
25.
Faure C, Patey N, Gauthier C, Brooks EM, Mawe GM. Serotonin signaling is altered in irritable bowel syndrome with diarrhea but not in functional dyspepsia in pediatric age patients. Gastroenterology 2010;139:249-58.  Back to cited text no. 25
    
26.
Yan C, Xin-Guang L, Hua-Hong W, Jun-Xia L, Yi-Xuan L. Effect of the 5-HT4 receptor and serotonin transporter on visceral hypersensitivity in rats. Braz J Med Biol Res 2012;45:948-54.  Back to cited text no. 26
    
27.
Zhang ZF, Duan ZJ, Wang LX, Yang D, Zhao G, Zhang L. The serotonin transporter gene polymorphism (5-HTTLPR) and irritable bowel syndrome: A meta-analysis of 25 studies. BMC Gastroenterol 2014;14:23.  Back to cited text no. 27
    
28.
Kumar S, Ranjan P, Mittal B, Ghoshal UC. Serotonin transporter gene (SLC6A4) polymorphism in patients with irritable bowel syndrome and healthy controls. J Gastrointestin Liver Dis 2012;21:31-8.  Back to cited text no. 28
    
29.
Kerckhoffs AP, ter Linde JJ, Akkermans LM, Samsom M. SERT and TPH-1 mRNA expression are reduced in irritable bowel syndrome patients regardless of visceral sensitivity state in large intestine. Am J Physiol Gastrointest Liver Physiol 2012;302:G1053-60.  Back to cited text no. 29
    
30.
Camilleri M, Andrews CN, Bharucha AE, Carlson PJ, Ferber I, Stephens D, et al. Alterations in expression of p11 and SERT in mucosal biopsy specimens of patients with irritable bowel syndrome. Gastroenterology 2007;132:17-25.  Back to cited text no. 30
    
31.
Wendland JR, Martin BJ, Kruse MR, Lesch KP, Murphy DL. Simultaneous genotyping of four functional loci of human SLC6A4, with a reappraisal of 5-HTTLPR and rs25531. Mol Psychiatry 2006;11:224-6.  Back to cited text no. 31
    
32.
Baudry A, Mouillet-Richard S, Schneider B, Launay JM, Kellermann O. miR-16 targets the serotonin transporter: A new facet for adaptive responses to antidepressants. Science 2010;329:1537-41.  Back to cited text no. 32
    
33.
Spiller R, Lam C. An update on post-infectious irritable bowel syndrome: Role of genetics, immune activation, serotonin and altered microbiome. J Neurogastroenterol Motil 2012;18:258-68.  Back to cited text no. 33
    
34.
Kekuda R, Torres-Zamorano V, Leibach FH, Ganapathy V. Human serotonin transporter: regulation by the neuroprotective agent aurintricarboxylic acid and by epidermal growth factor. J Neurochem 1997;68:1443-50.  Back to cited text no. 34
    
35.
Kubota N, Kiuchi Y, Nemoto M, Oyamada H, Ohno M, Funahashi H, et al. Regulation of serotonin transporter gene expression in human glial cells by growth factors. Eur J Pharmacol 2001;417:69-76.  Back to cited text no. 35
    
36.
Gil C, Najib A, Aguilera J. Serotonin transport is modulated differently by tetanus toxin and growth factors. Neurochem Int 2003;42:535-42.  Back to cited text no. 36
    

Top
Correspondence Address:
Dr. Yu-Ming Wang
Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin
China
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/sjg.SJG_333_17

Rights and Permissions


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

Top
  
 
  Search
 
  
  
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  


    Abstract
   Introduction
    Materials and Me...
   Results
   Discussion
   Conclusion
    References
    Article Figures

 Article Access Statistics
    Viewed1841    
    Printed12    
    Emailed0    
    PDF Downloaded338    
    Comments [Add]    

Recommend this journal