Roles of Gut Microbiota and Metabolites in Pathogenesis of Functional Constipation

Wang, Jun-Ke; Yao, Shu-Kun

doi:10.1155/2021/5560310

Cited by 99Gastrointestinal motility and disordersGut microbiota and healthProbiotics and Fermented Foods

Roles of Gut Microbiota and Metabolites in Pathogenesis of Functional Constipation

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Wang, Jun-Ke, Yao, Shu-Kun·2021·Evidence-Based Complementary and Alternative Medicine

DOI 10.1155/2021/5560310PMC PMC8481049

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Abstract

Functional constipation (FC), a condition characterized by heterogeneous symptoms (infrequent bowel movements, hard stools, excessive straining, or a sense of incomplete evacuation), is prevalent over the world. It is a multifactorial disorder and can be categorized into four subgroups according to different pathological mechanisms: normal transit constipation (NTC), slow transit constipation (STC), defecatory disorders (DD), and mixed type. Recently, growing evidence from human and animals has pointed that there was a strong association between gut microbiota and FC based on the brain-gut-microbiome axis. Studies have reported that the main characteristics of gut microbiota in FC patients were the relative decrease of beneficial bacteria such as Lactobacillus and Bifidobacterium, the relative increase of potential pathogens, and the reduced species richness. Gut microbiota can modulate gut functions through the metabolites of bacterial fermentation, among which short-chain fatty acids (SCFAs), secondary bile salts (BAs), and methane occupied more important positions and could trigger the release of gut hormones from enteroendocrine cells (EECs), such as 5-hydroxytryptamine (5-HT), peptide YY (PYY), and glucagon-like peptide-1 (GLP-1). Subsequently, these gut hormones can influence gut sensation, secretion, and motility, primarily through activating specific receptors distributed on smooth muscle cells, enteric neurons, and epithelial cells. However, research findings were inconsistent and even conflicting, which may be partially due to various confounding factors. Future studies should take the associated confounders into consideration and adopt multiomics research strategies to obtain more complete conclusions and to provide reliable theoretical support for exploring new therapeutic targets.

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Gut microbiota modulate gut functions via metabolite production such as short-chain fatty acids and bile acid, and indirect enteric neuroendocrine regulation in animals.
“the capability that gut microbiota modulate gut functions via metabolite production, such as short-chain fatty acids (SCFA) and bile acid, and indirect enteric neuroendocrine regulation in animals14.”
From Effects of dietary fibers or probiotics on functional constipation symptoms and roles of gut microbiota: a double-blinded randomized placebo trial (2023) · cites this paper as [14]
Functional constipation is associated with decreased beneficial species, increased pathogen species, and reduced species richness in humans.
“for the observations that functional constipation was associated with decreased beneficial species, increased pathogen species, and reduced species richness in human”
From Effects of dietary fibers or probiotics on functional constipation symptoms and roles of gut microbiota: a double-blinded randomized placebo trial (2023) · cites this paper as [14]
Gut microbiota disturbance plays a pathological role in functional constipation.
“Growing evidence has pointed to the pathological role of gut microbiota disturbance in functional constipation”
From Effects of dietary fibers or probiotics on functional constipation symptoms and roles of gut microbiota: a double-blinded randomized placebo trial (2023) · cites this paper as [14]

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Self-citation
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Effects of dietary fibers or probiotics on functional constipation symptoms and roles of gut microbiota: a double-blinded randomized placebo trial
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“Changes in microbial composition and metabolomics are related to the abnormality in neurotransmitter expression in the system, and would also influence the intestinal neuronal pathways that control intestinal sensorimotor function (69, 70) These neurotransmitters not only regulate blood flow, but also influence intest…”
Background
A key genetic factor governing arabinan utilization in the gut microbiome alleviates constipation
Zhang, C., Yu, L., Ma, C., Jiang, S., Zhang, Y., Wang, S., Tian, F., Xue, Y., Zhao, J., Zhang, H., et al. (2023) · Cell Host & Microbe · doi:10.1016/j.chom.2023.10.011 · Cited by 90 · see citing works
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“Dysbiosis refers to an abnormal composition and function of the microbial community in the gut, typically characterized by a decrease in beneficial bacteria such as bifidobacteria and lactobacilli and an increase in harmful bacteria such as Escherichia coli and Klebsiella [45, 46].”
Latilactobacillus sakei Furu2019 and stachyose as probiotics, prebiotics, and synbiotics alleviate constipation in mice
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“Additionally, prolonged retention of fecal matter can enhance gut bacterial fermentation and increase microbial toxins absorption, which may, in turn, influence behavior and neurological function in individuals with ASD [86].”
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“In particular, a crucial role seems to be played by the alteration of the rectal and pelvic floor functions through the brain-gut axis [17].”
Background
The associations of gut microbiota, endocrine system and bone metabolism
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“DCA can upregulate tph1 expression by activating TGR5, and thus promote gut 5-HT release, which may result in bone resorption (Alemi et al., 2013; Wang and Yao, 2021).”
Background
Chronic constipation and gut microbiota: current research insights and therapeutic implications
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Cannabis sativa L. alleviates loperamide-induced constipation by modulating the composition of gut microbiota in mice
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“Growing evidence has indicated that constipation is strongly associated with the gut microbiota (Wang and Yao, 2021; Zhang S. et al., 2021).”
Background
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“In addition, chemotactic peptides produced by gut flora, such as formyl-methionyl-leucyl-phenylalanine, stimulate the enteric nervous system, and primary afferents (30).”
Background
Enteric nervous system damage caused by abnormal intestinal butyrate metabolism may lead to functional constipation
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“When the CYP450 pathway is out of balance, the cycle of nerve cells will be disrupted, and the expression of cell cycle-related pathways and apoptosis-related pathways will be up-regulated, eventually leading to apoptosis (Wang and Yao, 2021).”
Background
Cinnamic acid regulates the intestinal microbiome and short-chain fatty acids to treat slow transit constipation
Jiang, J.-G., Luo, Q., Li, S., Tan, T.-Y., Xiong, K., Yang, T., & Xiao, T. (2023) · World Journal of Gastrointestinal Pharmacology and Therapeutics · doi:10.4292/wjgpt.v14.i2.4 · Cited by 26 · see citing works
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“Secondary bile acids and SCFAs, including acetate, propionate, and butyrate, could trigger the secretion of gut hormones, such as peptide YY (PYY), glucagon-like peptide-1 (GLP-1), and 5-hydroxytryptamine (5-HT) from intestinal epithelial cells [39–41].”
Background
Zhizhu decoction alleviates slow transit constipation by regulating aryl hydrocarbon receptor through gut microbiota
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“Gut microbiota and metabolites act as transit stations in this axis, and currently, increasing evidence from suggests a strong association between gut microbiota and functional constipation (Wang and Yao 2021; Zhang et al. 2021).”
Background
Rifaximin Ameliorates Loperamide-Induced Constipation in Rats through the Regulation of Gut Microbiota and Serum Metabolites
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“Hence SCFA, and, in particular, butyrate, can have both positive and negative effects on colonic motility, depending on its concentration [13].”
Background
Dietary Fiber as Prebiotics: A Mitigation Strategy for Metabolic Diseases
Gao, X., Hu, S.-M., Liu, Y., Alwis, S. D., Yu, Y., Li, Z.-F., Wang, Z.-Y., & Liu, J. (2025) · Foods · doi:10.3390/foods14152670 · Cited by 15 · see citing works
“SCFAs are the main metabolite of gut microbiota via DF fermentation, which influence the peristalsis and contraction of intestinal smooth muscle by reducing intestinal pH and promoting the production of intestinal peristalsis-related factors to relieve constipation [104].”
Unraveling the complexity of Disorders of the Gut-Brain Interaction: the gut microbiota connection in children
Rosa, D., Zablah, R. A., & Vázquez-Frías, R. (2024) · Frontiers in Pediatrics · doi:10.3389/fped.2023.1283389 · Cited by 15 · see citing works
“This detailed cascade underscores the multifaceted role of gut microbiota and their metabolites in shaping gut physiology and contributing to the development of functional constipation (24).”
Background
Effects of Liqi Tongbian decoction on gut microbiota, SCFAs production, and 5-HT pathway in STC rats with Qi Stagnation Pattern
Liu, Q., Ke, D., Chen, Y., Shen, A., Liu, L., Hu, L., Ren, Y., Fang, W., Zhao, P., Sferraf, T. J., et al. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2024.1337078 · Cited by 9 · see citing works
“Alterations in the relative abundance of beneficial and pathogenic bacteria in the gut flora can disrupt intestinal homeostasis, influencing the development and progression of STC (Wang and Yao, 2021).”
Background
The causal relationship between gut microbiota and constipation: a two-sample Mendelian randomization study
He, N., Sheng, K., Li, G., & Zhang, S. (2024) · BMC Gastroenterology · doi:10.1186/s12876-024-03306-8 · Cited by 13 · see citing works
Tryptophan Metabolism in Postmenopausal Women with Functional Constipation
Błońska, A., Chojnacki, M., Macieja, A., Błasiak, J., Majsterek, I., Chojnacki, J., & Popławski, T. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms25010273 · Cited by 13 · see citing works
“They regulate physiological functions, including colonic blood flow, fluid-end electrolyte reuptake, and modulation of gut motility [22,23].”
Background
Impact of Probiotics on the Prevention and Treatment of Gastrointestinal Diseases in the Pediatric Population
García-Santos, J. A., Nieto-Ruíz, A., García-Ricobaraza, M., Cerdó, T., & Campoy, C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24119427 · Cited by 17 · see citing works
“This imbalance is mediated by different mechanisms of action, including: (i) an increase in intestinal pH; (ii) a regulatory effect on the production of serotonin (5-HT), peptide YY and glucagon-like peptide-1 in enterochromaffin cells; and (iii) the potential activation of intrinsic primary afferent neurons via free…”
Background
Study on Anti-Constipation Effects of Hemerocallis citrina Baroni through a Novel Strategy of Network Pharmacology Screening
Liang, Y., Wei, X.-Q., Ren, R., Zhang, X., Tang, X., Yang, J., Wei, X.-Q., Huang, R., Hardiman, G., Sun, Y., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24054844 · Cited by 13 · see citing works
“The gut metabolites (SCOAs) are closely related to the development of constipation [26,27].”
Background
Can Lactose Intolerance Be a Cause of Constipation? A Narrative Review
Leszkowicz, J., Plata‐Nazar, K., & Szlagatys‐Sidorkiewicz, A. (2022) · Nutrients · doi:10.3390/nu14091785 · Cited by 14 · see citing works
The gut microbiota-constipation connection: Insights from a two sample bidirectional Mendelian randomization study
Zhou, J., Yuan, X., & Liu, Y. (2024) · Microbial Pathogenesis · doi:10.1016/j.micpath.2024.106667 · Cited by 12 · see citing works
Microbial imbalance in Chinese children with diarrhea or constipation
Ren, J., Ren, Y., Mu, Y., Zhang, L., Chen, B., Li, S.-S., Fang, Q., Zhang, Z., Zhang, K., Li, S., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-60683-6 · Cited by 11
“Here we have revealed a significant increase in gut microbiome diversity in children with constipation and a significant reduction in CD compared to HC, consistent with previous studies showing alterations in gut micro-biome characteristics in children with diarrhea or constipation 12,15,16 .”
Result
Gutted: constipation in children with chronic kidney disease and on dialysis
Wan, M., King, L., Baugh, N., Arslan, Z., Snauwaert, E., Paglialonga, F., & Shroff, R. C. (2023) · Pediatric Nephrology · doi:10.1007/s00467-022-05849-y · Cited by 13 · see citing works
“Current evidence points to various signal pathways mediated by the metabolites of bacterial fermentation, mediators released by the gut immune response, or intestinal neuroendocrine factors, of which short-chain fatty acids, bile salts, methane, and 5-hydroxytryptamine have been reported to play a role [40].”
Background
Alteration of the faecal microbiota composition in patients with constipation: evidence of American Gut Project
Xu, Y. S., Wang, Y. H., Liu, Y., Sun, X., Xu, J., Song, Y., Jiang, X., Xiong, Z., Tian, Z., & Zhang, C. P. (2022) · Beneficial Microbes · doi:10.3920/bm2022.0009 · Cited by 10 · see citing works
Loperamide-induced constipation is associated with excessive accumulation of bile acids and cholesterol in the liver of mice; attenuation by hesperidin
Li, J., Bi, D., Nie, Y., Wu, H., Lei, Y., Yu, S., Rong, H., Yang, Y., & Lei, Z. (2025) · Food and Chemical Toxicology · doi:10.1016/j.fct.2025.115561 · Cited by 7 · see citing works
Clinical effects of chemical drugs, fecal microbiota transplantation, probiotics, dietary fiber, and acupuncture in the treatment of chronic functional constipation: a systematic review and network meta-analysis
Tan, S.-F., Zhang, W., Zeng, P.-F., Yang, Y.-Y., Chen, S., Li, Y.-W., Bian, Y., & Xu, C. (2024) · European Journal of Gastroenterology and Hepathology · doi:10.1097/meg.0000000000002786 · Cited by 9 · see citing works
“Studies have found that patients with CFC exhibit a reduction in beneficial bacteria species, an increase in pathogenic species, and a decrease in overall species diversity [11].”
Background
Role of Pelvic Organ Crosstalk in Dysfunction of the Bowel and Bladder
Sinha, S., Vasudeva, P., Bharadwaj, S., & Mittal, A. (2022) · Current Bladder Dysfunction Reports · doi:10.1007/s11884-022-00645-8 · Cited by 9 · see citing works
Effect of honey-aloe paste on alleviating loperamide-induced constipation, in relation to regulation on gastrointestinal function and intestinal microenvironment
Chang, D., Wu, F., Yu, Y., Zhang, J., Ma, T., Guo, S., Zhao, H., & Cao, W. (2025) · Food Research International · doi:10.1016/j.foodres.2025.117006 · Cited by 8 · see citing works
Assessment of Urinary Dopamine and Serotonin Metabolites in Relation to Dysbiosis Indicators in Patients with Functional Constipation
Chojnacki, J., Popławski, T., Kaczka, A., Romanowska, N., Chojnacki, C. J., & Gąsiorowska, A. (2024) · Nutrients · doi:10.3390/nu16172981 · Cited by 7 · see citing works
Effect of Thumbtack Needle on Functional Constipation: A Pragmatic Randomized Controlled Trial.
Li, D., Zhang, G.-L., Zhang, L.-X., Tang, Y., Wang, L., Xu, Y., Cao, J., Zhao, W.-Q., Zuo, G.-C., Li, H., et al. (2024) · Complementary Therapies in Medicine · doi:10.1016/j.ctim.2024.103069 · Cited by 8 · see citing works
Functional Constipation and Obstructed Defecation
O'Donnell, M. T., & Haviland, S. (2023) · Surgical Clinics of North America · doi:10.1016/j.suc.2023.11.007 · Cited by 8 · see citing works
Ganoderma lucidum dietary fiber and lactobacillus fermentum CECT5716 alleviate constipation via regulation of gut barrier and microbiota
Wang, C., Zhang, Q., Wei, C., & Jin, Y. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.149010 · Cited by 4 · see citing works
Comprehensive microbial and clinical profiling of functional constipation: A stratified comparative study of age and constipation subtype
Zhu, H., Wang, H., Zhang, Q., Bai, J.-F., Wang, M., Du, S.-Y., & Zhang, Y. (2025) · World Journal of Gastroenterology · doi:10.3748/wjg.v31.i40.112637 · Cited by 6 · see citing works
Bifidobacterium Lactobacillus Triple Viable Alleviates Slow Transit Constipation by Regulating Gut Microbiota and Metabolism
Luo, M.-C., Xie, P.-W., Deng, X., Fan, J.-H., & Xiong, L.-S. (2025) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.16960 · Cited by 7 · see citing works
The association between constipation and anxiety: a cross-sectional study and Mendelian randomization analysis
Huang, Y.-X., Wang, Y.-B., Xu, B., Zeng, Y., Chen, P., Huang, Y.-S., & Liu, X.-Q. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1543692 · Cited by 7 · see citing works
A Low FODMAP Diet Supplemented with L-Tryptophan Reduces the Symptoms of Functional Constipation in Elderly Patients
Chojnacki, C. J., Mędrek-Socha, M., Błońska, A., Błasiak, J., Popławski, T., Chojnacki, J., & Gąsiorowska, A. (2024) · Nutrients · doi:10.3390/nu16071027 · Cited by 9 · see citing works
“Short-chain fatty acids (SCFAs), including indoleacetic acid (ILA), indole propionic acid (IPA), and butyric acid (EAA), regulate mucosal blood flow, fluid and electrolyte balance, and intestinal motility [52,53].”
Background
Bottom‐Up Design of Prebiotics and Probiotics: An Intestinal Microbiota‐Centered Approach to Chronic and Functional Constipation Management
He, P., Chen, S., Lyu, C., An, R., & Wang, D. (2025) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.70140 · Cited by 6 · see citing works
“Advances in gut microbiota research offer an opportunity to leverage the intricate relationship between intestinal microorganisms and host physiology [7–12].”
Application of traditional Chinese medicine nursing technology: Traditional Chinese medicine ironing combined with traditional Chinese medicine massage in improving functional constipation in elderly patients
Tan, L., Qin, W., Liao, J., Liu, Y., & Yan, L. (2024) · Medicine · doi:10.1097/md.0000000000039863 · Cited by 6 · see citing works
“[25] Massage therapy can stimulate acupoints, promote blood circulation, regulate intestinal immune response, thus balancing the proportion of intestinal flora and improving the frequency and characteristics of defecation.”
Background
Effect of prebiotic oligosaccharides on bowel habit and the gut microbiota in children with functional constipation (Inside study): study protocol for a randomised, placebo-controlled, multi-centre trial
Wegh, C. A. M., Schoterman, M., Vaughan, E., van der Zalm, S. C. C., Smidt, H., Belzer, C., & Benninga, M. (2024) · Trials · doi:10.1186/s13063-024-08050-8 · Cited by 6 · see citing works
Resistant effects determination of Lactobacillus supplementation on broilers to consecutive hydrogen sulfide exposure
Zhou, X., Hu, M., Luo, J., Xie, B., Ma, P., Wu, G., & Xue, F. (2023) · Poultry Science · doi:10.1016/j.psj.2023.103102 · Cited by 6
Assessment of the Gut Microbiome in Patients with Coexisting Irritable Bowel Syndrome and Chronic Fatigue Syndrome
Chojnacki, M., Błońska, A., Kaczka, A., Chojnacki, J., Walecka‐Kapica, E., Romanowska, N., Przybyłowska-Sygut, K., & Popławski, T. (2025) · Nutrients · doi:10.3390/nu17132232 · Cited by 5 · see citing works
Effects of dietary fiber on Chinese children with functional constipation and targeted modification of gut microbiota and related metabolites
Xiao, P., Song, T., Li, X. L., Xiao, Y. M., Wang, R. X., Song, F., Li, D., Zhang, A. H., Wang, Y., & Zhang, T. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1579668 · Cited by 3 · see citing works
“Furthermore, gut microbiota can influence gut functions through the production of metabolites, including short-chain fatty acids (SCFAs) and bile acids (18).”
The Potential Application of Aloe Barbadensis Mill. as Chinese Medicine for Constipation: Mini-Review
Huang, W.-R., Fang, Q.-H., Yu, X.-B., Ge, W., & Yu, Y. (2024) · Drug Design Development and Therapy · doi:10.2147/dddt.s446563 · Cited by 5 · see citing works
“62 Therefore, the relationship between gut microbiota and gut transit appears to be bidirectional.”
Background
Beyond nutrition: a comprehensive review of the multifaceted benefits of HMOs and Bifidobacterium -based synbiotics during early life
Wang, X., Xie, Q., Li, J., & Jiang, S. (2026) · Food & Function · doi:10.1039/d6fo00335d · Cited by 3 · see citing works
The role of intestinal gases in pediatric functional constipation: a narrative review of pathophysiology and emerging therapeutics
Zhou, Y., & Tao, E. (2026) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1694831 · Cited by 3 · see citing works
Dysbiosis of gut microbiota in children with functional constipation and damp-heat constitution: a cross-sectional multi-omics analysis
Zhao, H., Lu, X., Ye, Y., Li, W., Ye, H., Long, Z., Zhang, X., Wu, J., & Wang, J. (2025) · Scientific Reports · doi:10.1038/s41598-025-26439-6 · Cited by 2 · see citing works
“Additionally, Bifidobacterium promotes lactic acid production, leading to a lower intestinal pH, which enhances intestinal peristalsis 52,53 .”
Self-citation
Effect of Lactobacillus rhamnosus AB-GG combined with phototherapy on neonatal jaundice indicators, intestinal microbiota and metabolism
Yuan, Y., Chen, J.-Y., Liu, T., Chen, J.-J., Zhang, F., Shi, Z., & Zhang, J.-P. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1581242 · Cited by 3
“At the same time, B. longum which can promote intestinal peristalsis and inhibit the growth of harmful bacteria demonstrated a decrease (22).”
Probiotics interventions modulating gut microbiota composition in individuals with intestinal constipation: Protocol of a systemic review and meta-analysis of randomized controlled trials
Mei, Z., Du, P., Han, Y., Shao, Z., & Zheng, D. (2025) · PLoS ONE · doi:10.1371/journal.pone.0311799 · Cited by 3 · see citing works
Efficacy and mechanism of acupuncture for functional constipation in older adults: study protocol for a randomized controlled trial
Huai, Y., Fan, Q., Dong, Y., Li, X., Hu, J., Liu, L., Chen, Y., & Yin, P. (2024) · Frontiers in Neurology · doi:10.3389/fneur.2024.1341861 · Cited by 3 · see citing works
Characteristics of gut microbiota determine effects of specific probiotics strains in patients with functional constipation
Zhang, H., Sun, L.-J., Zhao, Z.-X., Zhou, Y., Liu, Y., Zhang, N., Yan, J., Wang, S.-B., Li, R., Zhang, J., et al. (2023) · Chinese Medical Journal · doi:10.1097/cm9.0000000000002826 · Cited by 3 · see citing works
“[2] Based on these findings, exogenous probiotics have been used in patients with constipation; however, few have produced consistent results.”
Background
Synergism of 2′-FL and Lactobacillus plantarum 1.0642 on gut microbiome diversity and functionality in constipated mice: A metagenomic analysis
Dou, N., Sun, C., Liu, Y., Wu, G., Feng, H., Chang, Y., Qian, S., & Hou, J. (2025) · Food Bioscience · doi:10.1016/j.fbio.2025.105976 · Cited by 2 · see citing works
Aurantii fructus immaturus (Rutaceae) flavonoid ameliorated constipation by regulating colonic microbiota and miRNA/mRNA network
Wen, Y., Zhan, Y., Du, L., Li, J., Shen, X.-L., He, B., Chen, T., & Tang, X. (2024) · Journal of Traditional and Complementary Medicine · doi:10.1016/j.jtcme.2024.11.011 · Cited by 1 · see citing works
“51 This study found that the mixed antibiotics reduced the number of OTU/ASV, and altered the composition and structure of the colonic microbiota in the AC mice and normal mice, suggesting the mixed antibiotics changed the composition and function of the colonic microbiota in the AC mice.”
Multi-omics combined to explore the purging mechanism of Rhei Radix et Rhizoma and Magnoliae Officinalis Cortex
Wang, Y., Zhang, Y. L., Wang, Q., Fan, Y., Li, W., Liu, M., Zhang, X., Zhou, W., Wang, M., Jiang, S., et al. (2024) · Journal of Chromatography B · doi:10.1016/j.jchromb.2024.124218 · Cited by 5 · see citing works
The effects of fermented vegetables on the gut microbiota for prevention of cardiovascular disease
Baron, M., Zuo, B., Chai, J., Zhao, J., Jahan-Mihan, A., Ochrietor, J., & Arikawa, A. Y. (2024) · Gut Microbiome · doi:10.1017/gmb.2024.4 · Cited by 4 · see citing works
“Individuals with a lower abundance of Lactobacillus may suffer from constipation (Wang and Yao, 2021).”
Background
Effects of Varied Sulfamethazine Dosage and Exposure Durations on Offspring Mice
Wang, H.-C., Dang, D., Zhu, L., Pan, M., Zhu, J., Lu, W.-W., Lu, S.-R., & Zhao, J.-X. (2024) · Microorganisms · doi:10.3390/microorganisms12020381 · Cited by 2 · see citing works
Subtyping intractable functional constipation in children using clinical and laboratory data in a classification model
Huang, Y.-H., Xie, C., Chou, C.-Y., Jin, Y., Li, W., Wang, M., Lu, Y., & Liu, Z. (2023) · Frontiers in Pediatrics · doi:10.3389/fped.2023.1148753 · Cited by 2 · see citing works
Oat β-glucans with different molecular weights modulate constipation through intestinal motility and gut microbiota metabolism
Wang, J., Liu, X., Li, Z., Zhang, W., Fang, B., Cheng, Y., & Qiu, J. (2026) · Journal of Functional Foods · doi:10.1016/j.jff.2026.107343 · Cited by 1 · see citing works
Self-citation
Viable gut bacterial metrics associated with intestinal eubiosis and dysbiosis
Naito, T., Setoyama, H., Kato‐Nagaoka, N., Shima, T., Sato, T., Moriyama-Ohara, K., Arase, S., Kurakawa, T., Horino-Higuchi, M., Tajima, S., et al. (2026) · Gut microbes reports · doi:10.1080/29933935.2026.2646054 · Cited by 1 · see citing works
“52,54,55 Constipation is closely linked to cardiovascular and renal diseases, with increased risk attributed to gut microbiota-derived metabolites such as trimethyl-amine-N-oxide, p -cresol sulfate, and indoxyl sulfate.”
Shaoyao Gancao decoction alleviates functional constipation by inhibiting Escherichia-Shigella expansion, modulating gut microbiota, and suppressing dysbiosis-induced endocannabinoid production: evidence from a self-controlled pilot study
Zhu, L., Gao, H., Li, Q., Wang, Y., Li, J., Li, X., Huang, Z., Wang, C., & Nie, J. (2025) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2025.1705271
Effectiveness of a Multispecies Synbiotic on Functional Constipation: A Randomized Controlled Trial
Veisari, A. K., Hajiebrahimi, S., Afra, H. S., Fakheri, H. T., Maleki, I., Taghvaei, T., Hosseini, V., Omrani‐Nava, V., Ebrahimi, M., Elhaei, A., et al. (2024) · Jundishapur Journal of Natural Pharmaceutical Products · doi:10.5812/jjnpp-141520
Association of Gut Flora and Short-Chain Fatty Acid Metabolite in Functional Constipation and Regulation of High-Fibre Diet on Them
Cai, Y.-W., Chen, S.-Y., & Zhang, W. (2023) · Highlights in Science Engineering and Technology · doi:10.54097/hset.v66i.11621 · Cited by 1 · see citing works
Chronic constipation in children: current approaches to diagnosis and treatment with osmotic laxatives. A review
Zakharova, I. N., Fayzullina, R. A., Berezhnaya, I. V., Medvedeva, E. A., Pupykina, V. V., & Orobinskaya, Y. V. (2026) · Pediatrics Consilium Medicum · doi:10.26442/26586630.2026.3.203812
Gut microbiota-driven imbalance of the gut-brain-immune homeostatic network in constipation: Pathogenic mechanisms and evolving therapeutic prospects
Zhu, J., Zeng, B., Zhu, W., Liu, Y., Li, X., Zhang, Y., Xu, Z., Xu, Q., Wu, W., Li, J., et al. (2026) · iScience · doi:10.1016/j.isci.2026.117850
Butyrate-Producing Bacteria in Regulating Intestinal Motility: Potential and Challenges
Liu, Q., Song, J., Huang, Z., Hu, L., Lin, Y., Huang, Y., Xu, Y., Ke, X., Huang, X., & Lin, Y. (2026) · Microorganisms · doi:10.3390/microorganisms14102283
“Studies have reported that germ-free mice or mice treated with antibiotics show reduced intestinal butyrate concentrations, increased expression of proglucagon (Gcg) in colonic L cells, and elevated plasma GLP-1 levels [33].”
Pilot Study of a Herbal Formulation Composed of Bidens pilosa for Constipation in Humans
Kuo, T., Lee, Y., Yang, G., Liang, Y., & Yang, W. (2026) · eFood · doi:10.1002/efd2.70205
Precision localization of the anus using a smart defecation assistance system based on the YOLOv11n model.
Wang, L., Wang, X., Shi, A., Wang, X.-W., Cheng, J., Deng, M., & Gou, L. (2026) · Technology and Health Care · doi:10.1177/09287329261485172
Co-exposure to nano-TiO2 and carbamazepine induces multidimensional toxicity in mussels, from physiological responses to gut microbiome dysbiosis
Chang, X.-X., Hu, M.-H., Shang, Y.-Y., Shen, S.-S., Lee, J.-S., Miao, J.-J., Dong, Y.-W., Maszczyk, P., Liu, B.-X., Zhang, M.-J., et al. (2026) · Water Biology and Security · doi:10.1016/j.watbs.2026.100722
Safety of treatments for children with functional constipation
van Os, T. M., Read, M. A., Wood, R. J., Lorenzo, C. D., Benninga, M. A., & Lu, P. L. (2026) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2026.2721396
Bioactive components of medicinal-food homology substances alleviating constipation via gut microbiota modulation: a review
Zhao, X., Song, Y., Zhu, J., Ma, B., Liang, D., Xu, Z., & Ma, Y. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1880189
“This activation promotes the synthesis and release of neuroactive substances, thereby precisely regulating intestinal motility (Wang and Yao, 2021).”
Gut microbiota and constipation: from causal evidence to therapeutic strategies—a state-of-the-art narrative review
Chen, Y., Duan, W., Du, M., Guo, M., & Sun, Y. (2026) · Frontiers in Microbiology · doi:10.3389/fmicb.2026.1817279
“Wang and Yao (2021) suggested that methane may act as a neuromuscular transmitter, affecting 5-HT levels and intestinal neuromuscular function; however, direct experimental validation in human tissues is still limited, and as discussed in Section 2.2, the direction of association is not consistent…”
Influential
Functional Constipation and Its Musculoskeletal and Biochemical Correlates in Pakistani Adults: A Cross-Sectional Study
Mir, U. Z., Ahmad, T., Tahir, A., Sajid, M., Mughal, F., & Yousaf, F. (2026) · Life Science · doi:10.37185/lns.1.1.1105
The effectiveness of a plant-based milk with fermented brown rice on constipation symptoms via gut microbiota modulation: a double-blind randomized controlled trial
Tang, A., Cao, Q., Wang, M.-H., Li, W., Xu, H.-K., Wang, Y., Niu, H.-Z., Wang, H., Ma, G.-Q., Jia, K., et al. (2026) · European Journal of Nutrition · doi:10.1007/s00394-026-04029-0
“Accumulating evidence have suggested the non-negligible roles of gut microbiota in gastro-intestinal disorders, including FC [18 ].”
Dietary management of functional bowel disorders in outpatient clinics: A retrospective audit.
Morley, S., & Utter, J. (2026) · Nutrition and Health · doi:10.1177/02601060261462770
Synbiotic Supplementation With Heyndrickxia coagulans TBC169 Improves Chronic Constipation in Middle‐Aged and Elderly
Zhou, X., Guo, C., Hu, G., Ding, L., Zou, T., Wang, M., Xiong, W., Deng, W., Wei, J., Yu, J., et al. (2026) · Biotechnology Journal · doi:10.1002/biot.70250
Lactobacillus acidophilus C4 ameliorates constipation in mice
Yan, H., Jia, Q., Liu, J., Hua, X., Cui, Y., Jian, W., Tan, Y., Oduor, O. S., Thomas, P., Kawimbe, M., et al. (2026) · Microbiology spectrum · doi:10.1128/spectrum.02950-25
“…intestinal mucosal barrier function and modulate host immune response to achieve multi-targeted interventions; and hence, generating biologically active metabolites, such as short-chain fatty acids, which indirectly modulate intestinal motility rhythms through the enteric-encephalic axis (12–14).”
Efficacy and Safety of Probiotics, Prebiotics and Synbiotics for the Treatment of Functional Constipation in Children: Systematic Review and Network Meta-analysis
Liang, C., Deng, X., Wang, H., Hu, X., Cui, L., Huang, J., Xu, M., Hou, L., Xu, S., Zhou, L., et al. (2026) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-026-10955-6
Deficiency of METTL3 alleviates excessive autophagy and apoptosis in mice with slow transit constipation and glutamic acid-induced interstitial cells of Cajal via the activation of PI3K/AKT pathway
Gong, W., Bu, F., Dai, Q., Xu, J.-L., & Yu, P. (2026) · Journal of Molecular Histology · doi:10.1007/s10735-025-10698-8
“STC pathogenesis may involve dysregulation of the intestinal motility regulatory system comprising the enteric nervous system (ENS), interstitial cells of Cajal (ICCs), and smooth muscle cells (Holland et al. 2025; Wang et al., 2021).”
Laxative Effect of Polysaccharides From Dendrobium officinale on Slow Transit Constipation: Regulation Effect of Intestinal Microbiota and 5‐HT System
Luo, D., Li, W., Zhang, C., Zhang, Z., & Ni, S.-Q. (2026) · Journal of food biochemistry · doi:10.1155/jfbc/2809212
Çocuklarda Fonksiyonel Kabızlığın Sıklığı, Klinik Özellikleri ve Kısa Dönem Tedavi Yanıtları: Türkiye’nin Güneydoğusunda Bir Üçüncü Basamak Merkez Deneyimi
Bozkaya, A., & Düztaş, D. T. (2025) · Harran üniversitesi tıp fakültesi dergisi · doi:10.35440/hutfd.1767984
Effects of Unilateral and Bilateral Sacral Nerve Stimulation on Defecation and Microbiota in Constipated Dogs.
Yi, T., Guo, X., Fang, Y., Liang, H., Lu, Y., Zhang, X., Cao, H., Liu, J.-Z., Wang, Q., Qu, Y., et al. (2025) · Neuromodulation (Malden, Mass.) · doi:10.1016/j.neurom.2025.10.065
Effects of a spore-forming probiotic blend on bowel habits and physical well-being in adults with functional constipation: A randomized, double-blind, placebo-controlled trial
Park, H. G., Lee, H. B., Lee, M., Park, H., Kang, M., Bok, M., Hwang, Y., Jeong, K., Maeng, S., Lim, H., et al. (2026) · PLoS ONE · doi:10.1371/journal.pone.0337019
“FC affects approximately 14% of the global population and is characterized by abdominal discomfort or pain, distension, and a sensation of incomplete evacuation [2–4].”
Lifestyle and Irritable Bowel Syndrome, the Viewpoints of Persian and Conventional Medicine: A Review Article
Mohebbi, M., Hasheminasab, F., Setayesh, M., Hatami, K., Naghizadeh, A., & Khadem, E. (2024) · Journal of Kerman University of Medical Sciences · doi:10.34172/jkmu.2024.43
Recent studies on gut-brain axis and irritable bowel syndrome
Chi, Z.-C. (2024) · World Chinese Journal of Digestology · doi:10.11569/wcjd.v32.i7.468
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Identification of a Key Genetic Factor Governing Arabinan Utilization in the Gut Microbiome Suggests a Novel Therapeutic Target for ConstipationPreprint
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MODULATION OF THE CONTRACTILE ACTIVITY IN THE SMOOTH MUSCLES OF THE COLON BY BIOLOGICALLY ACTIVE SUBSTANCES
Kirichek, P. (2024) · CHERKASY UNIVERSITY BULLETIN BIOLOGICAL SCIENCES SERIES · doi:10.31651/2076-5835-2018-1-2024-1-29-34
“The main of them are the dysfunctional disorders of cavity, wall and membrane digestion and absorption processes, as well as disruption of homeostasis in the intestinal microbiocenosis with the development of dysbacteriosis [11, 12].”
Background
CHANGES IN THE STRUCTURE OF THE COLON WALL TISSUES UNDERTHE INFLUENCE OF BIOLOGICALLY ACTIVE SUBSTANCES
Kirichek, P., & Lukyantseva, H. (2024) · Biology · doi:10.17721/1728.2748.2024.99.27-33
Overview of the Pathogenesis of Functional Constipation Based on “Deficiency Syndrome”
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Authors: Wang, J.-K., & Yao, S.-K.
Affiliations: Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
ORCID: Wang, Jun-Ke
Yao, Shu-Kun
Venue: Evidence-Based Complementary and Alternative Medicine
Publisher: Wiley
Published: 2021-09-21
Volume: 2021
Pages: 1-12
ISSN: 1741-427X (ISSN-L)
1741-4288
DOI: 10.1155/2021/5560310
PMC: PMC8481049
OpenAlex: W3199635008
Cited by: 98
References: 133
Citations by year: 2026: 12 · 2025: 20 · 2024: 26 · 2023: 26 · 2022: 14
FWCI: 3.15
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: Evidence-based Complementary and Alternative Medicine (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, other-oa)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics: Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
Keywords: functional constipation, gut microbiota, gut microbiota metabolites, gut-brain axis, short-chain fatty acids, secondary bile acids, methane, enteroendocrine hormones, serotonin, peptide YY, glucagon-like peptide-1, Lactobacillus, Bifidobacterium, intestinal motility, defecation disorders, slow transit constipation

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Roles of Gut Microbiota and Metabolites in Pathogenesis of Functional Constipation

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