Table 4 Limitations and future suggestions

Black et al. 2021 [59]

The diagnosis 0f IBS did not confirm, the questionnaire was online and it is unclear who responded to them or are those who answered suffering from IBS and whether their answers could be generalizable, since internet access is required, many could not participate and some people may have left the questionnaire in the middle. And finally, factors that affected the quality of life did not evaluate

Future studies need to predict underlying pathophysiological mechanisms in each cluster and, their specific treatments and, collect future treatment trials to achieve personal treatment

Han et al. [60]

Most of the participants were middle-aged Caucasian women so, it cannot be generalizable, and the cause-and-effect relationship between the characteristics of the patient and clusters could not be investigated

Future research should do the study based on ROME IV criteria, and asses the correlation between biomarkers and latent classes to target therapy

Lackner et al. 2013 [61]

The sample size is small and limited to just one clinic, there are some biases because of self-reported data, and k-means classification is not optimal however, there is no other choice because of the small sample size and also the symptoms intermittency could not assess

Future research should assess the biobehavioral variables and use instruments to define a subgroup scheme, and investigate the temporality of symptoms by longitudinal studies

Nevé et al. 2013 [63]

It cannot be generalized to all patients because of the small sample size and collect a sample from a tertiary center that has more severe IBS

Future research should be done in a larger population, analyze gut microbiota composition and compare the lactulose challenge test with a standard visceral sensitivity

Eslick et al. 2004 [42]

This questionnaire does not measure all of the diagnostic criteria, referral bias may be present because this physician has more IBS patients due to his specialty, and this study couldn’t compare the patients with other countries and show the temporality of symptoms

Future research should be larger and include more physician practices, including participants from different countries to investigate the effect of different cultures on functional gastrointestinal disorders

Guthrie et al. 2003 [51]

40% of patients refused rectal sensitivity measurements, this study cannot be generalized to all IBS patients because, it was conducted in secondary and tertiary centers and, in a severe range of patients

Future research must identify specific subgroups to develop target therapy

Ragnarsson et al. 1999 [52]

Medication use in sample 1 might influence the results

Future research should conduct to identify the pathophysiological mechanism of these subgroups and consequently target therapy in different patients

Howard Mertz et al. [57]

The sample size was small and reported symptom changes may have been affected by memory bias

Future studies should replicate these subgroups in other IBS populations, evaluate symptomatically correlates between patterns of physiologic parameters, and address regional autonomic abnormalities that might manifest by altered intestinal compliance, fluid, and electrolyte handling, and mucus secretion

Ragnarsson et al. 1999 [53]

This study could not show the association between pre- and post-prandial anorectal function and gastrointestinal symptoms

Future research should enroll more men to assess the sex difference in different parameters and, this method should repeat to identify the etiology and mechanism of the disease

Bouchoucha et al. 1999 [54]

In the present study, the use of visual detection of ultra-slow waves give little information about possible differences be- tween the two groups of subjects

More studies should be conducted to investigate whether these groups overlap or whether they include different groups of patients. The results of the present study must be compared with those of earlier studies of rectal slow waves

Bouchoucha et al. 2006 [55]

It has a selection bias because the study was conducted in a high-care center and rectal manometry was performed in people with constipation, which caused us to have more patients in this study than the general population

As regards, healthy people are not normally distributed in the current study, in future studies, researchers should be careful about the participants enrolled in the study

Bennet et al. 2018 [62]

The number of controls is very small compared to patients. Due to the nature of the study, it is not possible to determine whether cytokines have a delayed effect on symptoms or if they may have increased due to other reasons

Future research should conduct to identify the source of increased cytokines, cytokine cutoffs to identify immune-activated patients, the pathophysiology of immune activation in IBS, and, the way that triggers symptoms

Johanna Sundinet al. 2019 [56]

It is not able to identify the difference in the amount of mast cells and their proximity to the nerves in the large intestine mucosa of patients and controls

Future research should evaluate geographical differences in the pathophysiology of IBS by using standardized biopsy sampling, standardized inclusion, and exclusion criteria, and conducted in different geographical locations

Ian et al. 2014 [58]

It could not control probiotic consumption, which might theoretically cause confounding effects on microbiota composition

Future research should consider some antibiotic-free periods before sampling, and investigate microbial composition role in IBS