! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Differential Diagnosis for Constipation predominant symptoms}}
! style="background: #4479BA; width: 300px;" | {{fontcolor|#FFF|Similar Features}}
! style="background: #4479BA; width: 300px;" | {{fontcolor|#FFF|Differentiating Features}}
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| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |Strictures due to diverticultis,inflammatory bowel disease, ischemia or cancer
The exact pathogenesis of [disease name] is not fully understood.
OR
It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
OR
[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
OR
Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
OR
[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
OR
The progression to [disease name] usually involves the [molecular pathway].
OR
The pathophysiology of [disease/malignancy] depends on the histological subtype.
Discovery
Diagnostic criteria
Symptoms, signs and labs
1978: Manning
A threshold of at least three positive symptoms needs to be present to diagnose IBS with no duration of symptoms described under this classification.
1) Loose stools with onset of pain
2) Increased frequency of stools with onset of pain
3) Mucus per rectum
4) Visible distension of abdomen reported by the patient
5) Pain in the abdomen relieved by defecation
6) Sensation of incomplete evacuation
1984: Kruis
Symptoms of IBS must be present for more than two years. These symptoms include the following:
1. Pain in the abdomen, flatulence
2. Alternating constipation and diarrhea
Signs that exclude IBS are determined by the physician. They are as follows:
1. Abnormal physical findings and/or history suggestive of any other diagnosis
2. ESR more than 20mm/2h
3. Anemia(Hemoglobin < 12 for women or < 14 for men)
4. Leukocytosis > 10000/cc
Bleeding per rectum found on physical exam
1990: Rome Ⅰ
Abdominal discomfort or pain relieved with defecation or associated with change in frequency or consistency of stool in addition to two or more of the following (on at least twenty five percent of occasions/days for three months):
1. Altered stool form
2. Altered stool frequency
3. Altered stool passage
4. Passage of mucus in stool
5. Abdominal bloating or distension
1999: Rome Ⅱ
Pain in the abdomen or abdominal discomfort that has two of the following three features for twelve weeks(which may not be consecutive) in the last one year:
Onset associated with a change in stool form
Onset associated with alterations in stool frequency
Relief with defecation
2006: Rome Ⅲ
Recurrent pain in the abdomen or discomfort for three days in a month, for the last 3 months, associated with two or more of the following:
Onset associated with a change in stool form
Onset associated with a change in stool frequency
Improvement with defecation
2016: Rome IV
To establish the diagnosis, the patient must have recurrent pain in the abdomen (On an average, ≥1 day per week, in the previous 3 months) with an onset of ≥6 months before diagnosis-
Pain in the abdomen must be associated with at least two of the following:
Change in stool frequency
Change in stool appearance or form
Pain related to defecation
Patient must have none of the following warning signs:
Unintentional loss of weight
Age ≥50 years, without previous colon cancer screening
Recent change in bowel habit
Hematochezia or melena i.e. evidence of overt gastrointestinal bleeding
Nocturnal pain in the abdomen or passage of stools
History of inflammatory bowel disease or colorectal cancer in the family
Palpable abdominal mass or presence of lymphadenopathy
Positive fecal occult blood test
Blood testing showing evidence of iron deficiency anemia
[Disease name] was first discovered by [name of scientist], a [nationality + occupation], in [year]/during/following [event].
The association between [important risk factor/cause] and [disease name] was made in/during [year/event].
In [year], [scientist] was the first to discover the association between [risk factor] and the development of [disease name].
In [year], [gene] mutations were first implicated in the pathogenesis of [disease name].
Pathophysiology
Pathogenesis
The exact pathogenesis of Irritable Bowel Syndrome (IBS) is uncertain. It is understood that IBS is caused by the interaction of various factors:
Gastrointestinal motor abnormalities
IBS is referred to as ‘spastic colon’ due to changes in colonic motor function.
Manometry recordings from the transverse, descending and sigmoid colon have shown that spastic colon leads to changed patterns of colonic and small intestinal motor function such as increased frequency and irregularity of luminal contractions.[1][2][3]
Peak amplitude of high-amplitude propagating contractions (HAPCs) in diarrhea-prone IBS patients is higher, compared to healthy subjects.[4][5]
Diarrhea prone IBS patients have increased responses to ingestion, CRH(Corticotropin releasing hormone)[6][7], CCK(cholecystokinin)[8] and present with abdominal discomfort and accelerated transit through the colon.
On the other hand, constipation prone IBS patients show fewer HAPCs, delayed transit through the colon and decreased motility.[4]
It has been demonstrated that more than 90% of HAPCs are associated with abdominal pain.[8]
CNS dysregulation
The conceptualization of IBS being a brain gut disorder is reinforced by the following:
Epidemiological studies suggest that IBS occurs in individuals who have experienced childhood trauma, with symptom exacerbation occurring in patients with emotional disturbances or stress.[9]
Traumatic experiences before the age of 18 can directly shape adult connectivity in the executive control network. The effects on structures such as the insula, anterior cingulate cortex and the thalamus have been implicated in the pathophysiology of central pain amplification.[10]
IBS has been found to have a high association with pre-existing psychiatric and psychological conditions like anxiety and depression.[11] However, studies have shown that even when patients are not anxious or depressed, the dorsolateral prefrontal cortex activity is reduced, pointing directly towards CNS dysfunction and increased susceptibility to stressors.[12]
Psychological therapies that act on cerebral cortical sites and antidepressants have proven to be one of the mainstays of therapy for patients. The role of probiotics in modifying signal processing in the brain also proves that IBS is a brain gut disorder. [13]
Studies using advanced brain imaging techniques have analyzed differences in brain activity and have helped us appreciate that the mid-cingulate cortex (responsible for attention processes and responses) and the prefrontal cortex(responsible for vigilance and alertness of the human brain) are involved in IBS. [10]
Modulation of the mid-cingulate cortex is associated with alterations in the subjective sensations of pain whereas prefrontal cortex modulation may lead to increased perception of visceral pain.[10]
Patients with IBS have aberrant processing of central information,[14] with decreased feedback on the emotional arousal network that controls the autonomic modulation of gastrointestinal function.[15]These have been seen as irregularities on diffusion tensor imaging[16] in the white matter of the brain.
Rectal balloon distension in patients has shown the increased involvement of regions of the brain associated with attentional and behavioral responses to the arrival of such stimuli.[17][18][12]
Visceral hypersensitivity
Visceral hypersensitivity is an important factor in the pathogenesis of pain perception in IBS patients[19]. IBS is associated with a decreased threshold for perception of visceral stimuli[4][20] (i.e. visceral hypersensitivity).
Studies in IBS patients have shown that rectal balloon inflation produces painful and non-painful sensations at lower volumes as compared to healthy controls, suggesting the presence of afferent pathway disturbances in visceral innervation[21][22][23][24]. Many factors contribute to visceral hyperalgesia(i.e increased sensitivity of the intestines to normal sensations):
Spinal hyperexcitability due to activation of an N-methyl D aspartate(NMDA) receptor, Nitric oxide and possibly other neurotransmitters.
Activation of specific gastrointestinal mediators like kinins and serotonin that lead to afferent nerve fiber sensitization.
Central (brainstem and cortical) modulation with increased activation of anterior circulate cortex, thalamus and insula, involved in processing of pain, translating into long term hypersensitivity due to neuroplasticity, causing semipermanent changes in the neural response to all kinds of visceral stimulation. These findings have been proven by brain imaging studies. (e.g. functional magnetic resonance imaging, positron emission tomography)[20][25]
Recruitment of peripheral silent nociceptors causing increased end organ sensitivity due to hormonal or immune activation[20].
Immune activation and mucosal inflammation
The high prevalence of IBS in patients with history of inflammatory bowel disease, celiac disease or microscopic colitis points towards the fact that immune activation and mucosal inflammation play an important role in the pathogenesis of IBS.[26][27][28][29][30][31][28]
Moreover, psychological stress can significantly impact the release of proinflammatory cytokines, thereby affecting intestinal permeability and reinforcing a functional link existing between immune activation, psychological symptoms and symptoms in patients with IBS.[26]
Patients are found to have higher mucosal counts of lymphocytes (T cells, B cells), mast cells and immune mediators such as prostanoids, proteases, cytokines and histamines. [28][32][33][34][35]
Lymphocytes:
Patients with IBS have increased B lymphocyte activation in the blood.[36] However, activation of humoral immunity in IBS is specific for the gastrointestinal tract[37] as increased numbers of lymphocytes have been found in the small intestine and colon of patients.[27][29]
In addition to this, IBS patients with diarrhea[37] have enhanced mucosal humoral activity, associated with activation and proliferation of B cells and immunoglobulin production, identified by microarray profiling.
IBS patients with severe disease have an increase in lymphocyte infiltration in the myentric plexus,[29] in studies where full-thickness jejunal biopsies were obtained.
Mediators released by lymphocytes include histamine, proteases and nitric oxide. The stimulation of the enteric nervous system by these mediators leads to abnormal visceral and motor responses within the gastrointestinal tract.[27]
Examination of stool in patients with diarrhea prominent IBS have high levels of serine protease activity.[38][39]When fecal extracts are intra colonically infused into mice, there is increased visceral pain and colonic cellular permeability. [38]
Serine protease inhibitors prevent effects mediated by high levels of serine protease. Studies have shown that mononuclear cell supernatants in the peripheral blood from healthy controls have greater inhibitory effects on colorectal sensory afferent nerve endings than in IBS patients.[39][38]
Mast cells:
Studies have shown an increased number of mast cells in IBS patients in the jejunum, terminal ileum and colon.[31]
Higher numbers of activated mast cells are found in proximity to colonic nerve fibres in the mucosa of the gastrointestinal tract of IBS patients. [31][30]
Proinflammatory cytokines:
Cytokines are proteinaceous mediators of the immune response. Increased levels of cytokines have been found in IBS patients.[35][34]
Higher amounts of of tumor necrosis factor are produced by the peripheral blood mononuclear cells of IBS patients.[40][28]
In studies conducted using supernatants from cultured peripheral blood mononuclear cells in IBS patients,the TNF antagonist infliximab has been found to block the mechanical hypersensitivity of the mouse colonic afferent nerve endings. [41]
Other cytokines such as interleukin 1β, interleukin 6, interleukin 10 and TNFα have been found in increased amounts on analysis of the supernatants from IBS patients with diarrhea, as compared to healthy controls.Increased concentration of these cytokines is directly proportional to the severity and frequency of pain.[28][41][40]
Altered gut microbiota
It is postulated that altered fecal microflora may be associated with IBS.[42][32] There are numerous studies that suggest that altered fecal microflora in IBS patients differ from healthy controls. [43][44][45][46][47]
Inoculation of germ free animals with fecal microbiota from IBS patients has demonstrated increased colonic hypersensitivity, as compared to samples inoculated from healthy controls. [48]
Studies have also shown that the fecal microbiota in patients with post infectious IBS differs markedly from healthy controls, with decrease in the diversity of the fecal microbiome, correlated with increased numbers of CD8 and CD4RA-positive intraepithelial lymphocytes. [49]
IBS patients who have undergone colonoscopy, with sampling from the colon and terminal ileum have been found to have colonic spirochaetosis with a unique pathology of increased lymphoid follicles and eosinophils as compared to healthy controls.[50]
IBS with diarrhea is sometimes preceded by acute enteric infections and therefore, benefit from probiotics that serve to alter metabolism and composition of the microflora.[51][52] Administration of probiotics in patients decreases flatulence relative to Lactobacillus.[53] A probiotic yogurt containing a mixture of Bacteroides species has been shown to improve symptoms in IBS patients.[54]
Studies have been conducted suggesting that the switching on of a T-helper-2 immune-cell response may cause increased susceptibility to IBS after acute GI infection.[55][56]
Abnormal serotonin pathways
Neuroimmune factors
Genetic factors- Mutations in SCN5A encode alpha subunit of voltage gated sodium channel NaV1.5
Bile acid malabsorption- causes alteration of the function of an apical ileal bile acid transporter
Genetics
Genetics
IBS is a complex disease with interactions between genetic and environmental factors.[57][58] The role of genetic predisposition in IBS is suggested by epidemiological studies of twins[59][60] and familial aggregation.[58][58][61]
Investigations show higher concordance of IBS in monozygotic as compared to dizygotic twins, thereby proving the role of genetic factors in IBS.[58][60][62][63]
Effects of single nucleotide polymorphisms (SNPs) in genes of IBS patients have been extensively studied. SNPs in genes play an important role in host-microbiota interaction (TLR9, IL-6 and CDH1), immune activation and epithelial barriers.[64][65]
The mutation of type V (alpha subunit) of SCN5A-encoded voltage gated sodium channel associated with congenital prolonged QT syndrome can be correlated with symptoms of Irritable bowel syndrome. IBS patients with moderately severe pain in the abdomen have showed a missense mutation in SCN5A, causing loss of function of this channel, more commonly in patients with IBS associated with constipation.[66][67]
There is an established relationship between IBS and polymorphisms in the gene for serotonin transport causing alteration in intestinal peristalsis due to change in the serotonin reuptake efficacy.[68][69][70][71] Moreover, changed patterns of interleukin production may be associated with IBS.[65]
SNPs in tumour necrosis factor alpha (TNFα) and genes coding for superfamily member 15 (TNFSF15) that are associated with inflammatory bowel disease, have proven associations with IBS.[72][73][72]
Studies have been conducted to establish associations between neuropeptide S receptor gene (NPSR1) involved in nociception, inflammation and anxiety with abdominal pain.[74] TNF polymorphisms are also associated with post infectious IBS such as rs4263839 in TNFSF15 and IBS, particularly IBS-C.[73][72]
Genes involved in the regulation of hepatic bile acid synthesis such as a functional Klothoβ[75] gene variant also haven proven association with the disease.[76][75]
Data from studies suggest that the genome as well as genome-wide methylation of DNA plays an important role in IBS. Genome wide DNA methylation profiling is different in patients as compared to healthy controls, especially involving genes linked to neuropeptide hormone function and oxidative stress.[77]
Genetics
[Disease name] is transmitted in [mode of genetic transmission] pattern.
Genes involved in the pathogenesis of [disease name] include [gene1], [gene2], and [gene3].
The development of [disease name] is the result of multiple genetic mutations.
Associated Conditions
Gross Pathology
On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
Microscopic Pathology
On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
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↑Kumar D, Wingate DL (1985). "The irritable bowel syndrome: a paroxysmal motor disorder". Lancet. 2 (8462): 973–7. PMID2865504.
↑Simrén M, Castedal M, Svedlund J, Abrahamsson H, Björnsson E (2000). "Abnormal propagation pattern of duodenal pressure waves in the irritable bowel syndrome (IBS) [correction of (IBD)]". Dig. Dis. Sci. 45 (11): 2151–61. PMID11215731.
↑Kellow JE, Phillips SF (1987). "Altered small bowel motility in irritable bowel syndrome is correlated with symptoms". Gastroenterology. 92 (6): 1885–93. PMID3569764.
↑Whitehead WE, Engel BT, Schuster MM (1980). "Irritable bowel syndrome: physiological and psychological differences between diarrhea-predominant and constipation-predominant patients". Dig. Dis. Sci. 25 (6): 404–13. PMID7379673.
↑ 8.08.1Chey WY, Jin HO, Lee MH, Sun SW, Lee KY (2001). "Colonic motility abnormality in patients with irritable bowel syndrome exhibiting abdominal pain and diarrhea". Am. J. Gastroenterol. 96 (5): 1499–506. doi:10.1111/j.1572-0241.2001.03804.x. PMID11374689.
↑Elsenbruch S, Rosenberger C, Bingel U, Forsting M, Schedlowski M, Gizewski ER (2010). "Patients with irritable bowel syndrome have altered emotional modulation of neural responses to visceral stimuli". Gastroenterology. 139 (4): 1310–9. doi:10.1053/j.gastro.2010.06.054. PMID20600024.
↑Elsenbruch S, Rosenberger C, Enck P, Forsting M, Schedlowski M, Gizewski ER (2010). "Affective disturbances modulate the neural processing of visceral pain stimuli in irritable bowel syndrome: an fMRI study". Gut. 59 (4): 489–95. doi:10.1136/gut.2008.175000. PMID19651629.
↑Whitehead WE, Holtkotter B, Enck P, Hoelzl R, Holmes KD, Anthony J, Shabsin HS, Schuster MM (1990). "Tolerance for rectosigmoid distention in irritable bowel syndrome". Gastroenterology. 98 (5 Pt 1): 1187–92. PMID2323511.
↑ 20.020.120.2Barbara G, Cremon C, De Giorgio R, Dothel G, Zecchi L, Bellacosa L, Carini G, Stanghellini V, Corinaldesi R (2011). "Mechanisms underlying visceral hypersensitivity in irritable bowel syndrome". Curr Gastroenterol Rep. 13 (4): 308–15. doi:10.1007/s11894-011-0195-7. PMID21537962.
↑Mertz H, Naliboff B, Munakata J, Niazi N, Mayer EA (1995). "Altered rectal perception is a biological marker of patients with irritable bowel syndrome". Gastroenterology. 109 (1): 40–52. PMID7797041.
↑Posserud I, Syrous A, Lindström L, Tack J, Abrahamsson H, Simrén M (2007). "Altered rectal perception in irritable bowel syndrome is associated with symptom severity". Gastroenterology. 133 (4): 1113–23. doi:10.1053/j.gastro.2007.07.024. PMID17919487.
↑Bouin M, Plourde V, Boivin M, Riberdy M, Lupien F, Laganière M, Verrier P, Poitras P (2002). "Rectal distention testing in patients with irritable bowel syndrome: sensitivity, specificity, and predictive values of pain sensory thresholds". Gastroenterology. 122 (7): 1771–7. PMID12055583.
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↑ 26.026.1Coëffier M, Gloro R, Boukhettala N, Aziz M, Lecleire S, Vandaele N, Antonietti M, Savoye G, Bôle-Feysot C, Déchelotte P, Reimund JM, Ducrotté P (2010). "Increased proteasome-mediated degradation of occludin in irritable bowel syndrome". Am. J. Gastroenterol. 105 (5): 1181–8. doi:10.1038/ajg.2009.700. PMID19997094.
↑ 27.027.127.2Chadwick VS, Chen W, Shu D, Paulus B, Bethwaite P, Tie A, Wilson I (2002). "Activation of the mucosal immune system in irritable bowel syndrome". Gastroenterology. 122 (7): 1778–83. PMID12055584.
↑ 28.028.128.228.328.4Liebregts T, Adam B, Bredack C, Röth A, Heinzel S, Lester S, Downie-Doyle S, Smith E, Drew P, Talley NJ, Holtmann G (2007). "Immune activation in patients with irritable bowel syndrome". Gastroenterology. 132 (3): 913–20. doi:10.1053/j.gastro.2007.01.046. PMID17383420.
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↑ 31.031.131.2Barbara G, Stanghellini V, De Giorgio R, Cremon C, Cottrell GS, Santini D, Pasquinelli G, Morselli-Labate AM, Grady EF, Bunnett NW, Collins SM, Corinaldesi R (2004). "Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome". Gastroenterology. 126 (3): 693–702. PMID14988823.
↑ 32.032.1Marshall JK, Thabane M, Garg AX, Clark WF, Moayyedi P, Collins SM (2010). "Eight year prognosis of postinfectious irritable bowel syndrome following waterborne bacterial dysentery". Gut. 59 (5): 605–11. doi:10.1136/gut.2009.202234. PMID20427395.
↑Wensaas KA, Langeland N, Hanevik K, Mørch K, Eide GE, Rortveit G (2012). "Irritable bowel syndrome and chronic fatigue 3 years after acute giardiasis: historic cohort study". Gut. 61 (2): 214–9. doi:10.1136/gutjnl-2011-300220. PMID21911849.
↑ 34.034.1Mearin F, Perelló A, Balboa A, Perona M, Sans M, Salas A, Angulo S, Lloreta J, Benasayag R, García-Gonzalez MA, Pérez-Oliveras M, Coderch J (2009). "Pathogenic mechanisms of postinfectious functional gastrointestinal disorders: results 3 years after gastroenteritis". Scand. J. Gastroenterol. 44 (10): 1173–85. doi:10.1080/00365520903171276. PMID19711225.
↑Ohman L, Lindmark AC, Isaksson S, Posserud I, Strid H, Sjövall H, Simrén M (2009). "B-cell activation in patients with irritable bowel syndrome (IBS)". Neurogastroenterol. Motil. 21 (6): 644–50, e27. doi:10.1111/j.1365-2982.2009.01272.x. PMID19222763.
↑ 37.037.1Vicario M, González-Castro AM, Martínez C, Lobo B, Pigrau M, Guilarte M, de Torres I, Mosquera JL, Fortea M, Sevillano-Aguilera C, Salvo-Romero E, Alonso C, Rodiño-Janeiro BK, Söderholm JD, Azpiroz F, Santos J (2015). "Increased humoral immunity in the jejunum of diarrhoea-predominant irritable bowel syndrome associated with clinical manifestations". Gut. 64 (9): 1379–88. doi:10.1136/gutjnl-2013-306236. PMID25209656.
↑ 38.038.138.2Bueno L (2008). "Protease activated receptor 2: a new target for IBS treatment". Eur Rev Med Pharmacol Sci. 12 Suppl 1: 95–102. PMID18924448.
↑ 39.039.1Gecse K, Róka R, Ferrier L, Leveque M, Eutamene H, Cartier C, Ait-Belgnaoui A, Rosztóczy A, Izbéki F, Fioramonti J, Wittmann T, Bueno L (2008). "Increased faecal serine protease activity in diarrhoeic IBS patients: a colonic lumenal factor impairing colonic permeability and sensitivity". Gut. 57 (5): 591–9. doi:10.1136/gut.2007.140210. PMID18194983.
↑ 40.040.1Dinan TG, Quigley EM, Ahmed SM, Scully P, O'Brien S, O'Mahony L, O'Mahony S, Shanahan F, Keeling PW (2006). "Hypothalamic-pituitary-gut axis dysregulation in irritable bowel syndrome: plasma cytokines as a potential biomarker?". Gastroenterology. 130 (2): 304–11. doi:10.1053/j.gastro.2005.11.033. PMID16472586.
↑ 41.041.1Hughes PA, Moretta M, Lim A, Grasby DJ, Bird D, Brierley SM, Liebregts T, Adam B, Blackshaw LA, Holtmann G, Bampton P, Hoffmann P, Andrews JM, Zola H, Krumbiegel D (2014). "Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients". Brain Behav. Immun. 42: 191–203. doi:10.1016/j.bbi.2014.07.001. PMID25063707.
↑Ford AC, Thabane M, Collins SM, Moayyedi P, Garg AX, Clark WF, Marshall JK (2010). "Prevalence of uninvestigated dyspepsia 8 years after a large waterborne outbreak of bacterial dysentery: a cohort study". Gastroenterology. 138 (5): 1727–36, quiz e12. doi:10.1053/j.gastro.2010.01.043. PMID20117111.
↑Kassinen A, Krogius-Kurikka L, Mäkivuokko H, Rinttilä T, Paulin L, Corander J, Malinen E, Apajalahti J, Palva A (2007). "The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects". Gastroenterology. 133 (1): 24–33. doi:10.1053/j.gastro.2007.04.005. PMID17631127.
↑Malinen E, Rinttilä T, Kajander K, Mättö J, Kassinen A, Krogius L, Saarela M, Korpela R, Palva A (2005). "Analysis of the fecal microbiota of irritable bowel syndrome patients and healthy controls with real-time PCR". Am. J. Gastroenterol. 100 (2): 373–82. doi:10.1111/j.1572-0241.2005.40312.x. PMID15667495.
↑Rajilić-Stojanović M, Biagi E, Heilig HG, Kajander K, Kekkonen RA, Tims S, de Vos WM (2011). "Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome". Gastroenterology. 141 (5): 1792–801. doi:10.1053/j.gastro.2011.07.043. PMID21820992.
↑Jeffery IB, O'Toole PW, Öhman L, Claesson MJ, Deane J, Quigley EM, Simrén M (2012). "An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota". Gut. 61 (7): 997–1006. doi:10.1136/gutjnl-2011-301501. PMID22180058.
↑Crouzet L, Gaultier E, Del'Homme C, Cartier C, Delmas E, Dapoigny M, Fioramonti J, Bernalier-Donadille A (2013). "The hypersensitivity to colonic distension of IBS patients can be transferred to rats through their fecal microbiota". Neurogastroenterol. Motil. 25 (4): e272–82. doi:10.1111/nmo.12103. PMID23433203.
↑Sundin J, Rangel I, Fuentes S, Heikamp-de Jong I, Hultgren-Hörnquist E, de Vos WM, Brummer RJ (2015). "Altered faecal and mucosal microbial composition in post-infectious irritable bowel syndrome patients correlates with mucosal lymphocyte phenotypes and psychological distress". Aliment. Pharmacol. Ther. 41 (4): 342–51. doi:10.1111/apt.13055. PMID25521822.
↑Walker MM, Talley NJ, Inganäs L, Engstrand L, Jones MP, Nyhlin H, Agréus L, Kjellstrom L, Öst Å, Andreasson A (2015). "Colonic spirochetosis is associated with colonic eosinophilia and irritable bowel syndrome in a general population in Sweden". Hum. Pathol. 46 (2): 277–83. doi:10.1016/j.humpath.2014.10.026. PMID25540866.
↑Chassard C, Dapoigny M, Scott KP, Crouzet L, Del'homme C, Marquet P, Martin JC, Pickering G, Ardid D, Eschalier A, Dubray C, Flint HJ, Bernalier-Donadille A (2012). "Functional dysbiosis within the gut microbiota of patients with constipated-irritable bowel syndrome". Aliment. Pharmacol. Ther. 35 (7): 828–38. doi:10.1111/j.1365-2036.2012.05007.x. PMID22315951.
↑Camilleri M (2008). "Probiotics and irritable bowel syndrome: rationale, mechanisms, and efficacy". J. Clin. Gastroenterol. 42 Suppl 3 Pt 1: S123–5. doi:10.1097/MCG.0b013e3181574393. PMID18806702.
↑Nobaek S, Johansson ML, Molin G, Ahrné S, Jeppsson B (2000). "Alteration of intestinal microflora is associated with reduction in abdominal bloating and pain in patients with irritable bowel syndrome". Am. J. Gastroenterol. 95 (5): 1231–8. doi:10.1111/j.1572-0241.2000.02015.x. PMID10811333.
↑Maccaferri S, Candela M, Turroni S, Centanni M, Severgnini M, Consolandi C, Cavina P, Brigidi P (2012). "IBS-associated phylogenetic unbalances of the intestinal microbiota are not reverted by probiotic supplementation". Gut Microbes. 3 (5): 406–13. doi:10.4161/gmic.21009. PMID22713265.
↑Wouters MM, Van Wanrooy S, Nguyen A, Dooley J, Aguilera-Lizarraga J, Van Brabant W, Garcia-Perez JE, Van Oudenhove L, Van Ranst M, Verhaegen J, Liston A, Boeckxstaens G (2016). "Psychological comorbidity increases the risk for postinfectious IBS partly by enhanced susceptibility to develop infectious gastroenteritis". Gut. 65 (8): 1279–88. doi:10.1136/gutjnl-2015-309460. PMID26071133.
↑Wouters MM, Lambrechts D, Knapp M, Cleynen I, Whorwell P, Agréus L, Dlugosz A, Schmidt PT, Halfvarson J, Simrén M, Ohlsson B, Karling P, Van Wanrooy S, Mondelaers S, Vermeire S, Lindberg G, Spiller R, Dukes G, D'Amato M, Boeckxstaens G (2014). "Genetic variants in CDC42 and NXPH1 as susceptibility factors for constipation and diarrhoea predominant irritable bowel syndrome". Gut. 63 (7): 1103–11. doi:10.1136/gutjnl-2013-304570. PMID24041540.
↑ 58.058.158.258.3Levy RL, Jones KR, Whitehead WE, Feld SI, Talley NJ, Corey LA (2001). "Irritable bowel syndrome in twins: heredity and social learning both contribute to etiology". Gastroenterology. 121 (4): 799–804. PMID11606493.
↑ 60.060.1Lembo A, Zaman M, Jones M, Talley NJ (2007). "Influence of genetics on irritable bowel syndrome, gastro-oesophageal reflux and dyspepsia: a twin study". Aliment. Pharmacol. Ther. 25 (11): 1343–50. doi:10.1111/j.1365-2036.2007.03326.x. PMID17509102.
↑Saito YA, Petersen GM, Locke GR, Talley NJ (2005). "The genetics of irritable bowel syndrome". Clin. Gastroenterol. Hepatol. 3 (11): 1057–65. PMID16271334.
↑Morris-Yates A, Talley NJ, Boyce PM, Nandurkar S, Andrews G (1998). "Evidence of a genetic contribution to functional bowel disorder". Am. J. Gastroenterol. 93 (8): 1311–7. doi:10.1111/j.1572-0241.1998.440_j.x. PMID9707057.
↑Villani AC, Lemire M, Thabane M, Belisle A, Geneau G, Garg AX, Clark WF, Moayyedi P, Collins SM, Franchimont D, Marshall JK (2010). "Genetic risk factors for post-infectious irritable bowel syndrome following a waterborne outbreak of gastroenteritis". Gastroenterology. 138 (4): 1502–13. doi:10.1053/j.gastro.2009.12.049. PMID20044998.
↑Locke GR, Ackerman MJ, Zinsmeister AR, Thapa P, Farrugia G (2006). "Gastrointestinal symptoms in families of patients with an SCN5A-encoded cardiac channelopathy: evidence of an intestinal channelopathy". Am. J. Gastroenterol. 101 (6): 1299–304. doi:10.1111/j.1572-0241.2006.00507.x. PMID16771953.
↑ 72.072.172.2Swan C, Duroudier NP, Campbell E, Zaitoun A, Hastings M, Dukes GE, Cox J, Kelly FM, Wilde J, Lennon MG, Neal KR, Whorwell PJ, Hall IP, Spiller RC (2013). "Identifying and testing candidate genetic polymorphisms in the irritable bowel syndrome (IBS): association with TNFSF15 and TNFα". Gut. 62 (7): 985–94. doi:10.1136/gutjnl-2011-301213. PMID22684480.
Initially, IBS was considered a psychosomatic illness, and the involvement of biological and pathogenic factors was not verified until the 1990s, a process common in the history of emerging infectious diseases. The risk of developing IBS increases six-fold after acute gastrointestinal infection. Post-infection, further risk factors are young age, prolonged fever, anxiety and depression.[1]
Psychosomatic illness
One of the first references to the concept of an "Irritable Bowel" appeared in the Rocky Mountain Medical Journal in 1950.[2] The term was used to categorize patients who developed symptoms of diarrhea, abdominal pain, constipation, but where no well-recognized infective cause could be found. Early theories suggested that the Irritable Bowel was caused by a somatic, or mental disorder. One paper from the 1980s investigated "learned illness behavior" in patients with IBS and peptic ulcers.[3] Another study suggested that both IBS and stomach ulcer patients would benefit from 15 months of psychotherapy.[4] Later, it was found that most stomach ulcers were caused by a bacterial infection with Helicobacter pylori.[5]
Additional publications suggesting the role of brain-gut "axis" appeared in the 1990s, such as a study entitled Brain-gut response to stress and cholinergic stimulation in IBS published in the Journal of Clinical Gastrotnerology in 1993.[6] A 1997 study published in Gut magazine suggested that IBS was associated with a "derailing of the brain-gut axis."[7]
Most peptic ulcers are now treated with 1-2 weeks of antibiotic therapy, since it has been discovered that they are caused by a combination of a genetic trait in the patient and infection with the bacteria H. Pylori.[8]
Immune reaction
From the late 1990s, research publications began identifying specific biochemical changes present in tissue biopsies and serum samples from IBS patients that suggested symptoms had an organic rather than psychosomatic cause. These studies identified cytokines and secretory products in tissues taken from IBS patients. The cytokines identified in IBS patients produce inflammation and are associated with the body's immune response.
A study showed that intestinal biopsies from patients with constipation predominant IBS secreted higher levels of serotonin in-vitro.[9]Serotonin plays a role in regulating gastrointestinal motility and water content and can be altered by some diseases and infections.[10][11][12]
A study of rectal biopsy tissue from IBS patients showed increased levels of cellular structures involved in the production of the cytokine Interleukin 1 Beta.[13]
A study of intestinal biopsies from IBS patients showed increased levels of protease enzymes used by the body to digest proteins, and by infectious agents to combat the host's immune system.[15]
Specific forms of immune response that have been implicated in IBS symptoms include coeliac disease and other food allergy conditions.[17]Coeliac disease (also spelled "celiac") is an immunoglobulin type A-(IgA) mediated allergic response to the gliadin protein in gluten grains,which exhibits wide variety of symptoms and can present as IBS. "Some patients with diarrhea-predominant irritable bowel syndrome (IBS-D) may have undiagnosed celiac sprue (CS). Because the symptoms of CS respond to a gluten-free diet, testing for CS in IBS may prevent years of morbidity and attendant expense."[18] "Coeliac disease is a common finding among patients labelled as having irritable bowel syndrome. In this sub-group, a gluten free diet may lead to a significant improvement in symptoms. Routine testing for coeliac disease may be indicated in all patients being evaluated for irritable bowel syndrome."[19] Food allergies, particularly those mediated by IgE and IgG-type antibodies have been implicated in IBS.[20][21][22]
There is research to support IBS being caused by an as-yet undiscovered active infection. Most recently, a study has found that the antibiotic Rifaximin provides sustained relief for IBS patients.[23] While some researchers see this as evidence that IBS is related to an undiscovered agent, others believe IBS patients suffer from overgrowth of intestinal flora and the antibiotics are effective in reducing the overgrowth (known as small intestinal bacterial overgrowth).[24] Other researchers have focused on an unrecognized protozoal infection as a cause of IBS[25] as certain protozoal infections occur more frequently in IBS patients.[26][27] Two of the protozoa investigated have a high prevalence in industrialized countries and infect the bowel, but little is known about them as they are recently emerged pathogens.
Blastocystis is a single-celled organism which has been reported to produce symptoms of abdominal pain, constipation and diarrhea in patients, along with headaches and depression,[28] though these reports are contested by some physicians.[29] Studies from research hospitals in various countries have identified high Blastocystis infection rates in IBS patients, with 38% being reported from London School of Hygiene & Tropical Medicine,[30] 47% reported from the Department of Gastroenterology at Aga Khan University in Pakistan[26] and 18.1% reported from the Institute of Diseases and Public Health at University of Ancona in Italy.[27] Reports from all three groups indicate a Blastocystis prevalence of approximately 7% in non-IBS patients. Researchers have noted that clinical diagnostics fail to identify infection,[31] and Blastocystis may not respond to treatment with common antiprotozoals.[32][33][34][35]
Prevalence of protozoal infections in industrialized countries (United States and Canada) in 21st century.[36][37]
Dientamoeba fragilis is a single-celled organism which produces abdominal pain and diarrhea. Studies have reported a high incidence of infection in developed countries, and symptoms of patients resolve following antibiotic treatment.[36][38] One study reported on a large group of patients with IBS-like symptoms who were found to be infected with Dientamoeba fragilis and experienced resolution of symptoms following treatment.[39] Researchers have noted that methods used clinically may fail to detect some Dientamoeba fragilis infections.[38]
Pathophysiology
Pathogenesis
The exact pathogenesis of [disease name] is not fully understood.
OR
It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
The progression to [disease name] usually involves the [molecular pathway].
The pathophysiology of [disease/malignancy] depends on the histological subtype.
IBS is a diagnosis of [40][41]
Visceral hypersensitivity may have been utilized as a clinical marker of IBS and could be represented by signs and symptoms of urgency for bowel movements, bloating and abdominal pain. The mechanisms that result in persistent visceral hypersensitivity in patients who have IBS are unclear. nonetheless, various working models might be considered
↑Thabane M, Kottachchi DT, Marshall JK (2007). "The incidence and prognosis of post-infectious irritable bowel syndrome". Aliment Pharmacol Ther. 26 (4): 535–44. PMID17661757.CS1 maint: Multiple names: authors list (link)
↑BROWN PW (1950). "The irritable bowel syndrome". Rocky Mountain medical journal. 47 (5): 343–6. PMID15418074.
↑Whitehead WE, Winget C, Fedoravicius AS, Wooley S, Blackwell B (1982). "Learned illness behavior in patients with irritable bowel syndrome and peptic ulcer". Dig. Dis. Sci. 27 (3): 202–8. PMID7075418.CS1 maint: Multiple names: authors list (link)
↑Svedlund J, Sjödin I (1985). "A psychosomatic approach to treatment in the irritable bowel syndrome and peptic ulcer disease with aspects of the design of clinical trials". Scand. J. Gastroenterol. Suppl. 109: 147–51. PMID3895386.
↑Damianos AJ, McGarrity TJ (1997). "Treatment strategies for Helicobacter pylori infection". American family physician. 55 (8): 2765–74, 2784–6. PMID9191460.
↑Fukudo S, Nomura T, Muranaka M, Taguchi F (1993). "Brain-gut response to stress and cholinergic stimulation in irritable bowel syndrome. A preliminary study". J. Clin. Gastroenterol. 17 (2): 133–41. PMID8031340.CS1 maint: Multiple names: authors list (link)
↑Orr WC, Crowell MD, Lin B, Harnish MJ, Chen JD (1997). "Sleep and gastric function in irritable bowel syndrome: derailing the brain-gut axis". Gut. 41 (3): 390–3. PMID9378397.CS1 maint: Multiple names: authors list (link)
↑El-Omar EM, Carrington M, Chow WH; et al. (2000). "Interleukin-1 polymorphisms associated with increased risk of gastric cancer". Nature. 404 (6776): 398–402. doi:10.1038/35006081. PMID10746728.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
↑Miwa J, Echizen H, Matsueda K, Umeda N (2001). "Patients with constipation-predominant irritable bowel syndrome (IBS) may have elevated serotonin concentrations in colonic mucosa as compared with diarrhea-predominant patients and subjects with normal bowel habits". Digestion. 63 (3): 188–94. PMID11351146.CS1 maint: Multiple names: authors list (link)
↑McGowan K, Kane A, Asarkof N; et al. (1983). "Entamoeba histolytica causes intestinal secretion: role of serotonin". Science. 221 (4612): 762–4. PMID6308760.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
↑McGowan K, Guerina V, Wicks J, Donowitz M (1985). "Secretory hormones of Entamoeba histolytica". Ciba Found. Symp. 112: 139–54. PMID2861068.CS1 maint: Multiple names: authors list (link)
↑Gwee KA, Collins SM, Read NW; et al. (2003). "Increased rectal mucosal expression of interleukin 1beta in recently acquired post-infectious irritable bowel syndrome". Gut. 52 (4): 523–6. PMID12631663.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
↑Liebregts T, Adam B, Bredack C; et al. (2007). "Immune activation in patients with irritable bowel syndrome". Gastroenterology. 132 (3): 913–20. doi:10.1053/j.gastro.2007.01.046. PMID17383420.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
↑Cenac N, Andrews CN, Holzhausen M; et al. (2007). "Role for protease activity in visceral pain in irritable bowel syndrome". J. Clin. Invest. 117 (3): 636–47. doi:10.1172/JCI29255. PMID17304351.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
↑Hussain R, Jaferi W, Zuberi S; et al. (1997). "Significantly increased IgG2 subclass antibody levels to Blastocystis hominis in patients with irritable bowel syndrome". Am. J. Trop. Med. Hyg. 56 (3): 301–6. PMID9129532.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
↑Wangen, Dr. Stephen. The Irritable Bowel Syndrome Solution. 2006. ISBN 0976853787. Excerpted with author's permission at [1]
↑Spiegel BM; et al. (2004). "Testing for celiac sprue in irritable bowel syndrome with predominant diarrhea: a cost-effectiveness analysis". Gastroenterology. 126 (7): 1721–32. PMID15188167.CS1 maint: Explicit use of et al. (link)
↑Shahbazkhani B; et al. (2003). "Coeliac disease presenting with symptoms of irritable bowel syndrome". Aliment Pharmacol Therapy. 18 (2): 231–5. PMID12869084.CS1 maint: Explicit use of et al. (link)
↑Li H; et al. (2007). "Allergen-IgE complexes trigger CD23-dependent CCL20 release from human intestinal epithelial cells". Gastroenterology. 133 (6): 1905–15. PMID18054562.CS1 maint: Explicit use of et al. (link)
↑"The therapeutic effects of eliminating allergic foods according to food-specific IgG antibodies in irritable bowel syndrome - Article in Chinese". Zhonghua Nei Ke Za Zhi. 46 (8): 641–3. 2007. PMID17967233. Text "Yang CM, Li YQ " ignored (help)
↑Drisko; et al. (2006). "Treating Irritable Bowel Syndrome with a Food Elimination Diet Followed by Food Challenge and Probiotics". Journal of the American College of Nutrition. 25 (6): 514–22. PMID17229899.CS1 maint: Explicit use of et al. (link)
↑Pimentel M, Park S, Mirocha J, Kane SV, Kong Y (2006). "The effect of a nonabsorbed oral antibiotic (rifaximin) on the symptoms of the irritable bowel syndrome: a randomized trial". Ann. Intern. Med. 145 (8): 557–63. PMID17043337.CS1 maint: Multiple names: authors list (link)
↑Posserud I, Stotzer PO, Björnsson ES, Abrahamsson H, Simrén M (2007). "Small intestinal bacterial overgrowth in patients with irritable bowel syndrome". Gut. 56 (6): 802–8. doi:10.1136/gut.2006.108712. PMID17148502.CS1 maint: Multiple names: authors list (link)
↑Stark D, van Hal S, Marriott D, Ellis J, Harkness J (2007). "Irritable bowel syndrome: a review on the role of intestinal protozoa and the importance of their detection and diagnosis". Int. J. Parasitol. 37 (1): 11–20. doi:10.1016/j.ijpara.2006.09.009. PMID17070814.CS1 maint: Multiple names: authors list (link)
↑ 26.026.1Yakoob J, Jafri W, Jafri N; et al. (2004). "Irritable bowel syndrome: in search of an etiology: role of Blastocystis hominis". Am. J. Trop. Med. Hyg. 70 (4): 383–5. PMID15100450.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
↑ 27.027.1Giacometti A, Cirioni O, Fiorentini A, Fortuna M, Scalise G (1999). "Irritable bowel syndrome in patients with Blastocystis hominis infection". Eur. J. Clin. Microbiol. Infect. Dis. 18 (6): 436–9. PMID10442423.CS1 maint: Multiple names: authors list (link)
↑Qadri SM, al-Okaili GA, al-Dayel F (1989). "Clinical significance of Blastocystis hominis". J. Clin. Microbiol. 27 (11): 2407–9. PMID2808664.CS1 maint: Multiple names: authors list (link)
↑Markell EK, Udkow MP (1986). "Blastocystis hominis: pathogen or fellow traveler?". Am. J. Trop. Med. Hyg. 35 (5): 1023–6. PMID3766850.
↑Stensvold R, Brillowska-Dabrowska A, Nielsen HV, Arendrup MC (2006). "Detection of Blastocystis hominis in unpreserved stool specimens by using polymerase chain reaction". J. Parasitol. 92 (5): 1081–7. PMID17152954.CS1 maint: Multiple names: authors list (link)
↑Yakoob J, Jafri W, Jafri N, Islam M, Asim Beg M (2004). "In vitro susceptibility of Blastocystis hominis isolated from patients with irritable bowel syndrome". Br. J. Biomed. Sci. 61 (2): 75–7. PMID15250669.CS1 maint: Multiple names: authors list (link)
↑Haresh K, Suresh K, Khairul Anus A, Saminathan S (1999). "Isolate resistance of Blastocystis hominis to metronidazole". Trop. Med. Int. Health. 4 (4): 274–7. PMID10357863.CS1 maint: Multiple names: authors list (link)
↑Markell EK, Udkow MP (1986). "Blastocystis hominis: pathogen or fellow traveler?". Am. J. Trop. Med. Hyg. 35 (5): 1023–6. PMID3766850.
↑Ok UZ, Girginkardeşler N, Balcioğlu C, Ertan P, Pirildar T, Kilimcioğlu AA (1999). "Effect of trimethoprim-sulfamethaxazole in Blastocystis hominis infection". Am. J. Gastroenterol. 94 (11): 3245–7. PMID10566723.CS1 maint: Multiple names: authors list (link)
↑ 36.036.1Lagacé-Wiens PR, VanCaeseele PG, Koschik C (2006). "Dientamoeba fragilis: an emerging role in intestinal disease". CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 175 (5): 468–9. doi:10.1503/cmaj.060265. PMID16940260.CS1 maint: Multiple names: authors list (link)
↑Amin OM (2002). "Seasonal prevalence of intestinal parasites in the United States during 2000". Am. J. Trop. Med. Hyg. 66 (6): 799–803. PMID12224595.
↑ 38.038.1Stensvold CR, Arendrup MC, Mølbak K, Nielsen HV (2007). "The prevalence of Dientamoeba fragilis in patients with suspected enteroparasitic disease in a metropolitan area in Denmark". Clin. Microbiol. Infect. 13 (8): 839–42. doi:10.1111/j.1469-0691.2007.01760.x. PMID17610603.CS1 maint: Multiple names: authors list (link)
↑Borody T, Warren E, Wettstein A; et al. (2002). "Eradication of Dientamoeba fragilis can resolve IBS-like symptoms". J Gastroenterol Hepatol. 17 (Suppl, pages=A103).CS1 maint: Missing pipe (link) CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
