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Keimyung Med J > Volume 43(2); 2024 > Article
Yang, Lee, and Park: An Association between Telomere Length and Irritable Bowel Syndrome in Korean Populations

Abstract

Telomere shortening has been suggested as an indicator of aging and psychiatric disorders. However, few studies have explored the relationship between telomere length (TL) and irritable bowel syndrome (IBS). We investigated the association between TL and IBS in 43 IBS patients using quantitative polymerase chain reaction. The clinical characteristics and severity of IBS, assessed by the visual analogue scale, were also analyzed. The average TL was 4.40 ± 3.87, with TL shortening tending to be associated with female sex and smoking. However, these associations did not reach statistical significance. Correlation analysis showed a negative correlation between IBS severity and TL (r = –0.285, p = 0.083), although this was not statistically significant. No other clinical characteristics were significantly associated with TL. This is the first study to examine the relationship between TL and IBS. Our findings suggest that TL may have potential as a predictor for IBS diagnosis.

Introduction

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by chronic abdominal pain, diarrhea, constipation, and fluctuating bowel movement patterns between constipation and diarrhea. Some patients may also experience bloating, a feeling of incomplete bowel evacuation, and general discomfort [1]. Approximately 11% of the global population is affected by IBS, with female representing 55% of those impacted [2,3]. Its prevalence ranges from 10% to 25% in the United States, 17% to 21% in South America, 7% to 9% in South Asia, and 5.6% in the Middle East and Africa [2-4]. Notably, the prevalence of IBS is higher among college students in their 20s compared to other age groups [5]. Recent studies suggest that IBS poses social, economic, and psychological challenges, significantly affecting quality of life. Additionally, diagnosing and treating IBS can be difficult due to its influence on the visceral-brain axis, which is linked to mental health issues such as anxiety and depression [6].
Telomeres are specialized structures located at the ends of chromosomes that, along with their associated protein complexes, protect DNA and maintain genomic stability [7]. Each cell division results in the loss of telomeric repeats due to the incomplete replication of the chromosome’s 3’ end, leading to critically short telomeres that can trigger cellular senescence or crisis [8]. Telomere length (TL) progressively decreases with age; however, this decline is accelerated by oxidative stress and inflammation. TL is established at birth in individuals and reflects the cumulative effects of inflammation and oxidative stress throughout life [9,10]. Telomeres may be linked to various diseases, particularly those related to aging and neurodegeneration [11-13]. However, there was only one study about telomere change and its clinical characteristics in IBS patients [14]. This study showed that patients with IBS presented shorter TL when compared to healthy controls. For better understand this relationship, we aimed to determine clinical characteristics of patients with IBS and telomere in this study. As telomere may vary depending on age and genetic status, this study was performed in college students without hereditary disorder.

Methods

Participants

Participants who met the inclusion criteria were recruited through advertisements on bulletin boards in Daegu, South Korea. The inclusion criteria were as follows: (1) college students aged 18 years or older; (2) those who fulfilled the Rome III Diagnostic Criteria for IBS [1]; (3) no prior history of surgeries or diagnosed gastrointestinal disorders, such as obstructive bowel disorders, inflammatory bowel diseases, or lactose malabsorption; and (4) no previous history of psychiatric illnesses. A total of 43 participants with IBS were contacted. The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board of Keimyung University (40525-201809-BR-84-02).
The severity of IBS symptoms was assessed by previous criteria [15]. These criteria include seven items, and after excluding the categorical questions regarding the presence of abdominal pain or bloating, the remaining five questions were rated on a visual analogue scale (VAS), each worth 100 points. The questions are as follows: Q1 = abdominal pain, Q2 = bloating and flatulence, Q3 = bowel habits (diarrhea and constipation), Q4 = perception of psychological well-being, and Q5 = daily life-related gastrointestinal problem. The severity was determined by the total score of these five items, classified as follows: 75–174 = mild, 175–299 = moderate, and 300–500 = severe. Our previous study indicated that the reproducibility of this scale at the time of development was stable at 85%, with a Cronbach’s α value of 0.72 reflecting its reliability.

DNA extraction

Blood samples were collected from 43 participants to obtain serum. Informed consent was verbally obtained from all participants and/or their legal guardians. The Institutional Review Board of Keimyung University Dongsan Medical Center approved the research protocols. Genomic DNA was extracted from the serum using a DNA extraction kit (Qiagen Inc.). The quantity and quality of the extracted DNA were assessed using a NanoDrop 1000 (Thermo Fisher Scientific).

Telomere length analysis

The TL of each chromosome was analyzed by quantitative polymerase chain reaction (qPCR). To analyze quantitative TL relative to nuclear DNA (S), primers for assessing the TL were selected using specific amplification (T) and ß-globin primers were used for nuclear DNA, according to a previous study [16]. qPCR was performed using the LightCycler 480 II system (Roche Diagnostics). TL was presented as T/S values and calculated as follows: T/S = 2 − ΔCt where ∆Ct = average Ct telomere – average Ct ß-globin. Each measurement was performed in triplicate and five serially diluted control samples were included in each experiment.

Statistical analysis

All statistical analyses were conducted using the SPSS statistical software, version 25.0, for Windows (IBM Corp.). The chi-square test was employed to examine the associations between the variables. A two-tailed p-value of less than 0.05 was regarded as indicating statistical significance.

Results

In the present study, TL was successfully measured in all 38 participants. The average TL was 4.40 ± 3.87, and participants were categorized into high and low TL groups based on the median value. The clinical characteristics of individuals with IBS and their TL were examined, with the findings summarized in Table 1. IBS was classified into three subtypes: diarrhea-predominant, constipation-predominant, and mixed types, none of which showed a significant association with TL. Female and smoking habits showed a tendency towards shorter TL, although these associations were not statistically significant (p = 0.192 and p = 0.157, respectively). Other clinical characteristics did not demonstrate any relationship with TL.
The average severity score of IBS symptoms in this study was 319.42 ± 64.84. Correlation analysis indicated a trend towards a negative association between IBS severity and TL (r = –0.285, p = 0.083; Fig. 1), although this relationship was not statistically significant. The correlation between VAS scores and TL was also examined, with the results shown in Table 2. TL was found to be negatively correlated with bloating (Q2) (r = –0.283, p = 0.086), though this correlation did not reach statistical significance. Most of VAS scores correlated to each other.

Discussion

Telomeres, the protective caps at the ends of chromosomes, have been implicated in the pathogenesis of various diseases. In numerous chronic conditions, such as cardiovascular diseases, diabetes, and neurodegenerative disorders, telomere shortening has been associated with cellular aging and tissue dysfunction [9-11]. TL serves as a biomarker of cellular health, as its reduction reflects diminished replicative capacity of cells, leading to increased susceptibility to disease. In cancer, while short telomeres can contribute to genomic instability and tumorigenesis, some cancers exhibit abnormally long telomeres that enable uncontrolled cell division [16,17]. As such, understanding the role of telomeres in disease mechanisms could offer new insights into disease prevention, prognosis, and potential therapeutic strategies.
A previous study demonstrated that patients with IBS had significantly shorter telomeres compared to healthy controls [14]. Moreover, TL was shorter in IBS patients attributed to mental or psychological factors than in those affected by other factors. Interestingly, TL was longer in IBS patients who had taken antidepressants. In this study, we also confirmed the relationship between TL and the clinical features of IBS. To control for variables related to age and TL, the study was conducted exclusively with patient groups from specific age ranges. Unexpectedly, TL was found not to be associated with any clinical characteristics of IBS.
In this study, we observed a potential correlation between TL and the severity of IBS, although this correlation did not reach statistical significance. Our findings suggest that more severe IBS symptoms are associated with shorter TL, which is consistent with previous research indicating shorter TL in individuals with IBS compared to healthy controls [14]. Additionally, telomere shortening was linked to symptoms such as bloating and flatulence. Several studies have shown that mental and psychological factors in IBS are associated with shorter telomeres [18,19]. The stress induced by the severity of IBS may contribute to cellular senescence, leading to telomere shortening. Several hypotheses have been proposed to explain this mechanism. For example, changes in the intestinal microbiome in IBS may alter physiological and metabolic processes, potentially triggering cellular senescence [20,21]. Other research suggests that elevated glucocorticoid levels in IBS could accelerate stress-related aging of the epigenome, promoting telomere shortening [22,23]. However, the precise mechanisms underlying telomere regulation in IBS remain unclear, and further studies are needed to explore the detailed molecular pathways involved.
This is the first study to explore the relationship between IBS severity and TL; however, it has some limitations. The sample size was small, and there is a lack of data on the progression of IBS. Additionally, the VAS is subjective, as it assesses disease severity based on a questionnaire. Therefore, further long-term follow-up studies using objective experimental models are needed. IBS is not classified as a major disease, but, ongoing research is essential to improve the quality of life for patients.

Notes

Acknowledgements

None.

Ethics approval

The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board of Keimyung University (40525-201809-BR-84-02).

Conflict of interest

The authors have nothing to disclose.

Funding

None.

Fig. 1.
Negative correlation between IBS severity and telomere length. IBS, irritable bowel syndrome.
kmj-2024-00122f1.jpg
Table 1.
Clinical significance of TL in irritable bowel syndrome
Variable TL p-value
Shorter Longer
Subtype 0.372
 Diarrhea-predominant 2 (66.7) 1 (33.3)
 Constipation-predominant 0 (0) 1 (100)
 Mixed 23 (67.6) 11 (32.4)
Sex 0.192
 Male 2 (40.0) 3 (60.0)
 Female 23 (69.7) 10 (30.3)
Smoking 0.157
 No 22 (71.0) 9 (29.0)
 Yes 3 (42.9) 4 (57.1)
Drinking 0.715
 No 15 (68.2) 7 (31.8)
 Yes 10 (62.5) 6 (37.5)
Sleep partner 0.653
 No 19 (67.9) 9 (32.1)
 Yes 6 (60.0) 4 (40.0)
Night duty 0.510
 No 18 (69.2) 8 (30.8)
 Yes 7 (58.3) 5 (41.7)
Cardiovascular disease 0.160
 No 25 (67.6) 12 (32.4)
 Yes 0 (0) 1 (100)
Inflammatory bowel disease 0.351
 No 19 (70.4) 8 (29.6)
 Yes 6 (54.5) 5 (45.5)
Anxietas tibiarum 0.653
 No 19 (67.9) 9 (32.1)
 Yes 6 (60.0) 4 (40.0)
Visual analogue scale 0.353
 Mild 0 (0) 1 (100)
 Moderate 7 (63.6) 4 (34.1)
 Severe 18 (69.2) 8 (30.8)

Values are presented as number (%).

TL, telomere length.

Table 2.
Correlation between visual analogue scale and TL
Variable TL Age Q1 Q2 Q3 Q4 Q5 Sum
TL
 r 1 0.092 –0.157 –0.283 –0.081 –0.205 –0.074 –0.285
p-value 0.581 0.346 0.086 0.627 0.217 0.660 0.083
Age
 r 1 –0.329* –0.132 0.086 0.114 0.270 0.015
p-value 0.031 0.398 0.583 0.466 0.080 0.924
Q1
 r 1 0.506** –0.070 –0.067 –0.023 0.380*
p-value 0.001 0.657 0.671 0.883 0.012
Q2
 r 1 –0.061 –0.008 0.063 0.521**
p-value 0.699 0.961 0.686 0.000
Q3
 r 1 0.655** 0.407** 0.709**
p-value 0.000 0.007 0.000
Q4
 r 1 0.286 0.716**
p-value 0.063 0.000
Q5
 r 1 0.535**
p-value 0.000

TL, telomere length; Q1, abdominal pain; Q2, bloating and flatulence; Q3, bowel habits (diarrhea and constipation); Q4, perception of psychological well-being; Q5, daily life-related GI problem.

*p < 0.05, ** p < 0.01.

References

1. Canavan C, West J, Card T. The epidemiology of irritable bowel syndrome. Clin Epidemiol. 2014;6:71–80.
crossref pmid pmc
2. Liu Y, Liu L, Yang Y, He Y, Zhang Y, Wang M, et al. A school-based study of irritable bowel syndrome in medical students in Beijing, China: prevalence and some related factors. Gastroenterol Res Pract. 2014;2014:124261.
crossref pmid pmc pdf
3. Shiotani A, Miyanishi T, Takahashi T. Sex differences in irritable bowel syndrome in Japanese university students. J Gastroenterol. 2006;41:562–8.
crossref pmid pdf
4. Cain KC, Headstrom P, Jarrett ME, Motzer SA, Park H, Burr RL, et al. Abdominal pain impacts quality of life in women with irritable bowel syndrome. Am J Gastroenterol. 2006;101:124–32.
crossref pmid
5. Yang YY, Jun S. Prevalence and associated factors of insomnia in college students with irritable bowel syndrome. Korean J Adult Nurs. 2018;30:235–44.
crossref pdf
6. Ida M, Nishida A, Akiho H, Nakashima Y, Matsueda K, Fukudo S. Evaluation of the irritable bowel syndrome severity index in Japanese male patients with irritable bowel syndrome with diarrhea. Biopsychosoc Med. 2017;11:7.
crossref pmid pmc pdf
7. Masutomi K, Possemato R, Wong JM, Currier JL, Tothova Z, Manola JB, et al. The telomerase reverse transcriptase regulates chromatin state and DNA damage responses. Proc Natl Acad Sci U S A. 2005;102:8222–7.
crossref pmid pmc
8. Maser RS, DePinho RA. Connecting chromosomes, crisis, and cancer. Science. 2002;297:565–9.
crossref pmid
9. Aviv A. Telomeres and human aging: facts and fibs. Sci Aging Knowledge Environ. 2004;2004:pe43.
crossref pmid
10. Steer SE, Williams FM, Kato B, Gardner JP, Norman PJ, Hall MA, et al. Reduced telomere length in rheumatoid arthritis is independent of disease activity and duration. Ann Rheum Dis. 2007;66:476–80.
crossref pmid pmc
11. Panossian LA, Porter VR, Valenzuela HF, Zhu X, Reback E, Masterman D, et al. Telomere shortening in T cells correlates with Alzheimer’s disease status. Neurobiol Aging. 2003;24:77–84.
crossref pmid
12. Houben JM, Moonen HJ, van Schooten FJ, Hageman GJ. Telomere length assessment: biomarker of chronic oxidative stress? Free Radic Biol Med. 2008;44:235–46.
crossref pmid
13. Savage SA, Alter BP. The role of telomere biology in bone marrow failure and other disorders. Mech Ageing Dev. 2008;129:35–47.
crossref pmid pmc
14. Zhang Y, Fu F, Zhang L, Zhang W, Chen L, Zhang Y, et al. Telomere is shortened in patients with irritable bowel syndrome in the Chinese population. J Gastroenterol Hepatol. 2022;37:1749–55.
crossref pmid pdf
15. Francis CY, Morris J, Whorwell PJ. The irritable bowel severity scoring system: a simple method of monitoring irritable bowel syndrome and its progress. Aliment Pharmacol Ther. 1997;11:395–402.
crossref pmid
16. Jung SJ, Kil SH, Lee HW, Park TI, Lee YH, Kim J, et al. Clinical characteristics of TZAP (ZBTB48) in hepatocellular carcinomas from tissue, cell line, and TCGA. Medicina (Kaunas). 2022;58:1778.
crossref pmid pmc
17. Jung SJ, Cho JH, Park WJ, Heo YR, Lee JH. Telomere length is correlated with mitochondrial DNA copy number in intestinal, but not diffuse, gastric cancer. Oncol Lett. 2017;14:925–9.
crossref pmid pmc
18. Schutte NS, Malouff JM. The association between depression and leukocyte telomere length: a meta-analysis. Depress Anxiety. 2015;32:229–38.
crossref pmid
19. Ridout KK, Ridout SJ, Price LH, Sen S, Tyrka AR. Depression and telomere length: a meta-analysis. J Affect Disord. 2016;191:237–47.
crossref pmid pmc
20. Schippa S, Conte MP. Dysbiotic events in gut microbiota: impact on human health. Nutrients. 2014;6:5786–805.
crossref pmid pmc
21. Bhattarai Y, Muniz Pedrogo DA, Kashyap PC. Irritable bowel syndrome: a gut microbiota-related disorder? Am J Physiol Gastrointest Liver Physiol. 2017;312:G52–G62.
crossref pmid pmc
22. Kennedy PJ, Cryan JF, Quigley EM, Dinan TG, Clarke G. A sustained hypothalamic-pituitary-adrenal axis response to acute psychosocial stress in irritable bowel syndrome. Psychol Med. 2014;44:3123–34.
crossref pmid
23. Gassen NC, Chrousos GP, Binder EB, Zannas AS. Life stress, glucocorticoid signaling, and the aging epigenome: implications for aging-related diseases. Neurosci Biobehav Rev. 2017;74:356–65.
crossref pmid
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