Small intestinal bacterial overgrowth as a cause for irritable bowel syndrome

Purpose of review Small intestinal bacterial overgrowth (SIBO) has been proposed as a cause of irritable bowel syndrome (IBS). However, this relationship has been subject to controversy. This review aims to provide a current perspective on the SIBO-IBS hypothesis. Recent findings Case–control studies evaluating the prevalence of SIBO in IBS and healthy individuals have shown conflicting results. Moreover, the tests available in routine clinical practice to diagnose SIBO are not valid and lack both sensitivity and specificity. Hence, interpreting the effect of interventions based on these tests is fraught with uncertainty. Furthermore, the SIBO-IBS hypothesis has paved the way to assess antibiotic therapy in nonconstipated IBS, with rifaximin, a nonabsorbable antibiotic, showing modest but significant clinical benefit. However, individuals were not tested for SIBO and the mechanism of action of rifaximin in IBS remains to be elucidated. Preliminary data suggest that rifaximin decreases microbial richness and previous studies have noted antibacterial interventions in IBS to reduce colonic fermentation and improve symptoms. The advent of rapid culture-independent molecular techniques is a promising tool that will seek to clarify and advance our understanding of the gut microbial function. Summary The SIBO-IBS hypothesis lacks convincing evidence but remains under scrutiny. The mechanism resulting in symptom improvement after rifaximin treatment in some IBS individuals requires exploration. Novel molecular techniques provide an exciting and challenging opportunity to explore the host–gut microbiota interaction

An approach to the diagnosis and management of Rome IV functional disorders of chronic constipation

Introduction: Chronic constipation is highly prevalent, affecting between 10% and 15% of the population. The Rome IV criteria categorizes disorders of chronic constipation into four subtypes: (a) functional constipation, (b) irritable bowel syndrome with constipation, (c) opioid-induced constipation, and (d) functional defecation disorders, including inadequate defecatory propulsion and dyssynergic defecation. The initial management approach for these disorders is similar, focusing on diet, lifestyle and the use of standard over-the-counter laxatives. If unsuccessful, further therapy is tailored according to subtype. Areas covered: This review covers the definition, epidemiology, diagnostic criteria, investigations and management of the Rome IV disorders of chronic constipation. Expert opinion: By adopting a logical step-wise approach toward the diagnosis of chronic constipation and its individual subtypes, clinicians have the opportunity to tailor therapy accordingly and improve symptoms, quality of life, and patient satisfaction

Neurochemical biomarkers to study CNS effects of COVID-19: a narrative review and synthesis

Neurological symptoms are frequently reported in patients suffering from COVID-19. Common CNS-related symptoms include anosmia, caused by viral interaction with either neurons or supporting cells in nasal olfactory tissues. Diffuse encephalopathy is the most common sign of CNS dysfunction, which likely results from the CNS consequences of the systemic inflammatory syndrome associated with severe COVID-19. Additionally, microvascular injuries and thromboembolic events likely contribute to the neurologic impact of acute COVID-19. These observations are supported by evidence of CNS immune activation in cerebrospinal fluid (CSF) and in autopsy tissue, along with detection of microvascular injuries in both pathological and neuroimaging studies. The frequent occurrence of thromboembolic events in patients with COVID-19 has generated different hypotheses, among which viral interaction with perivascular cells is particularly attractive, yet unproven. A distinguishing feature of CSF findings in SARS-CoV-2 infection is that clinical signs characteristic of neurotropic viral infections (CSF pleocytosis and blood brain barrier injury) are mild or absent. Moreover, virus detection in CSF is rare, and often of uncertain significance. In this review, we provide an overview of the neurological impact that occur in the acute phase of COVID-19, and the role of CSF biomarkers in the clinical management and research to better treat and understand the disease. In addition to aiding as diagnostic and prognostic tools during acute infection, the use of comprehensive and well characterized CSF and blood biomarkers will be vital in understanding the potential impact on the CNS in the rapidly increasing number of individuals recovering from COVID-19

Irritable bowel syndrome: what do the new Rome IV diagnostic guidelines mean for patient management?

The Rome criteria are universally used as inclusion criteria in pharmaceutical clinical trials and have therefore contributed to testing of several irritable bowel syndrome (IBS)-specific drugs. However, clinicians do not routinely use them because they are complex and consequently difficult to remember. Revised Rome diagnostic criteria for IBS and other functional gastrointestinal disorders (FGIDs) were published in May 2016

Management of the multiple symptoms of irritable bowel syndrome

Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders. A stepwise management approach is advocated for patients with IBS. For a substantial proportion of patients with mild symptoms, general management principles, including making a confident diagnosis and offering explanation, reassurance, and dietary and lifestyle advice, are sufficient. However, many patients continue to have moderate-to-severe symptoms and are not satisfied solely with this approach. In these patients, use of pharmacotherapy on the basis of the predominant symptom (constipation, diarrhoea, pain, or bloating) or combination of symptoms is the next step. For patients with symptoms that are refractory to these initial treatment options and those who have comorbid conditions or psychological symptoms, a combination of therapies should be used, and the use of psychotropic drugs and psychological treatment alternatives is often effective. Finally, the key to successful treatment of patients with IBS is a good physician–patient relationship and use of person-centred care principles

Infection of brain pericytes underlying neuropathology of covid‐19 patients

A wide range of neurological manifestations have been associated with the development of COVID‐19 following SARS‐CoV‐2 infection. However, the etiology of the neurological sympto-matology is still largely unexplored. Here, we used state‐of‐the‐art multiplexed immunostaining of human brains (n = 6 COVID‐19, median age = 69.5 years; n = 7 control, median age = 68 years) and demonstrated that expression of the SARS‐CoV‐2 receptor ACE2 is restricted to a subset of neuro-vascular pericytes. Strikingly, neurological symptoms were exclusive to, and ubiquitous in, patients that exhibited moderate to high ACE2 expression in perivascular cells. Viral dsRNA was identified in the vascular wall and paralleled by perivascular inflammation, as signified by T cell and macro-phage infiltration. Furthermore, fibrinogen leakage indicated compromised integrity of the blood– brain barrier. Notably, cerebrospinal fluid from additional 16 individuals (n = 8 COVID‐19, median age = 67 years; n = 8 control, median age = 69.5 years) exhibited significantly lower levels of the pericyte marker PDGFRβ in SARS‐CoV‐2‐infected cases, indicative of disrupted pericyte homeostasis. We conclude that pericyte infection by SARS‐CoV‐2 underlies virus entry into the privileged central nervous system space, as well as neurological symptomatology due to perivascular inflammation and a locally compromised blood–brain barrier

How the Change in IBS Criteria From Rome III to Rome IV Impacts on Clinical Characteristics and Key Pathophysiological Factors

Objectives: The diagnostic criteria for irritable bowel syndrome (IBS) have recently been updated from Rome III to Rome IV. Whereas in Rome III a diagnosis of IBS entailed chronic abdominal pain or discomfort at least 3 days per month, in Rome IV the term discomfort has been removed and the frequency of abdominal pain increased to at least 1 day per week. We examined how this change in IBS criteria impacts on clinical characteristics and pathophysiological factors. Methods: A total of 542 Swedish subjects with Rome III IBS completed a baseline questionnaire enquiring for the number of abdominal pain days in the last 10 days; this was subsequently used as a surrogate marker to identify Rome IV IBS, in that (a) those with 0 or 1 day of pain were classed as Rome IV-negative, and (b) those with ≥2 days of pain were classed as Rome IV-positive. Comparisons were made between Rome IV-positive and -negative IBS groups for demographics, IBS subtype, gastrointestinal and psychological symptoms, somatisation, fatigue, disease-specific quality of life, rectal sensitivity, and oro-anal transit time. Results: Overall, 85% of Rome III IBS patients fulfilled the Rome IV criteria for IBS, but 15% did not. Rome IV-positive subjects were significantly more likely to be female, have poorer quality of life, greater pain severity, bloating, somatisation, fatigue, and rectal sensitivity than Rome IV-negative subjects. There were no differences in severity of anxiety or depression, IBS subtypes, bowel habit dissatisfaction, or oro-anal transit time. Finally, increasing number of pain days correlated positively with symptoms and visceral hypersensitivity. Conclusions: Most Rome III-positive IBS patients seeking healthcare fulfil the Rome IV IBS criteria. They constitute a more severe group than those who lose their IBS diagnosis

Neurochemical signs of astrocytic and neuronal injury in acute COVID-19 normalizes during long-term follow-up

Background: Neurologic manifestations are well-recognized features of coronavirus disease 2019 (COVID-19). However, the longitudinal association of biomarkers reflecting CNS impact and neurological symptoms is not known. We sought to determine whether plasma biomarkers of CNS injury were associated with neurologic sequelae after COVID-19. / Methods: Patients with confirmed acute COVID-19 were studied prospectively. Neurological symptoms were recorded during the acute phase of the disease and at six months follow-up, and blood samples were collected longitudinally. Healthy age-matched individuals were included as controls. We analysed plasma concentrations of neurofilament light-chain (NfL), glial fibrillary acidic protein (GFAp), and growth differentiation factor 15 (GDF-15). / Findings: One hundred patients with mild (n = 24), moderate (n = 28), and severe (n = 48) COVID-19 were followed for a median (IQR) of 225 (187–262) days. In the acute phase, patients with severe COVID-19 had higher concentrations of NfL than all other groups (all p < 0·001), and higher GFAp than controls (p < 0·001). GFAp was also significantly increased in moderate disease (p < 0·05) compared with controls. NfL (r = 0·53, p < 0·001) and GFAp (r = 0·39, p < 0·001) correlated with GDF-15 during the acute phase. After six months, NfL and GFAp concentrations had normalized, with no persisting group differences. Despite this, 50 patients reported persistent neurological symptoms, most commonly fatigue (n = 40), “brain-fog” (n = 29), and changes in cognition (n = 25). We found no correlation between persistent neurological symptoms and CNS injury biomarkers in the acute phase. / Interpretation: The normalization of CNS injury biomarkers in all individuals, regardless of previous disease severity or persisting neurological symptoms, indicates that post COVID-19 neurological sequelae are not accompanied by ongoing CNS injury. / Funding: The Swedish State Support for Clinical Research, SciLifeLab Sweden, and the Knut and Alice Wallenberg Foundation have provided funding for this project

The prevalence and impact of overlapping Rome IV-diagnosed functional gastrointestinal disorders on somatization, quality of life, and healthcare utilization: A cross-sectional general population study in three countries

all P <0.001. Notably, individuals with FGIDs in multiple regions had greater somatization and worse QOL than organic GI disease controls. CONCLUSIONS: Roughly a third of the general adult population fulfi ls diagnostic criteria for a Rome IV FGID. In a third of this subset multiple GI regions are involved and this overlap is associated with increased health impairment.OBJECTIVES: The population prevalence of Rome IV-diagnosed functional gastrointestinal disorders (FGIDs) and their cumulative effect on health impairment is unknown. METHODS: An internet-based cross-sectional health survey was completed by 5,931 of 6,300 general population adults from three English-speaking countries (2100 each from USA, Canada, and UK). Quota-based sampling was used to generate demographically balanced and population representative samples with regards to age, sex, and education level. The survey enquired for demographics, medication, surgical history, somatization, quality of life (QOL), doctor-diagnosed organic GI disease, and criteria for the Rome IV FGIDs. Comparisons were made between those with Rome IV-diagnosed FGIDs against non-GI (healthy) and organic GI disease controls. RESULTS: The number of subjects having symptoms compatible with a FGID was 2,083 (35%) compared with 3,421 (57.7%) non-GI and 427 (7.2%) organic GI disease controls. The most frequently met diagnostic criteria for FGIDs was bowel disorders ( n =1,665, 28.1%), followed by gastroduodenal ( n =627, 10.6%), anorectal ( n =440, 7.4%), esophageal ( n =414, 7%), and gallbladder disorders ( n =10, 0.2%). On average, the 2,083 individuals who met FGID criteria qualifi ed for 1.5 FGID diagnoses, and 742 of them (36%) qualifi ed for FGID diagnoses in more than one anatomic region. The presence of FGIDs in multiple regions was associated with increasing somatization, worse mental/physical QOL, more medical therapies, and a higher prevalence of abdominal surgerie

Epidemiology, clinical characteristics, and associations for symptom-based Rome IV functional dyspepsia in adults in the USA, Canada, and the UK: a cross-sectional population-based study

Background: The population prevalence, clinical characteristics, and associations for Rome IV functional dyspepsia are not known. Following the publication of the Rome IV criteria for functional gastrointestinal disorders, we aimed to assess the prevalence, characteristics, and associations for symptom-based Rome IV functional dyspepsia in adults across the USA, Canada, and the UK. Methods: We sent an internet-based cross-sectional health survey to adults in the general population of three English-speaking countries: the USA, Canada, and the UK. We used quota-based sampling to generate demographically balanced and population-representative samples. Individuals were invited to complete an online questionnaire on general health, without mention that the purpose of this survey was to examine gastrointestinal symptoms. We excluded participants who failed two attention-test questions or were excessively inconsistent on the three gastrointestinal questions that were presented twice in the survey for this particular purpose. The survey enquired about demographics, health-care visits, medications, somatisation, quality of life, and symptom-based criteria for Rome IV functional dyspepsia as well as for irritable bowel syndrome (IBS) and functional heartburn. We made subsequent comparisons between participants with Rome IV functional dyspepsia and controls without dyspepsia. The primary objective was to identify participants who fulfilled symptom-based criteria for Rome IV functional dyspepsia and categorise them into postprandial distress syndrome, epigastric pain syndrome, or overlapping subtypes. Findings: 6300 general population adults completed the health survey; 2100 each from the USA, Canada, and the UK. 369 responses were deemed inconsistent, leaving data for 5931 adults. Rome IV functional dyspepsia was significantly more prevalent in the USA (232 [12%] of 1949) than in Canada (167 [8%] of 1988) and the UK (152 [8%] of 1994; p<0·0001). The subtype distribution was 61% postprandial distress syndrome, 18% epigastric pain syndrome, and 21% overlapping variant with both syndromes; this pattern was similar across the countries. Participants with functional dyspepsia had significantly greater health impairment and health-care usage than those without dyspepsia. Participants with the overlapping variant showed greater somatisation and poorer quality-of-life scores than did individuals with either postprandial distress syndrome or epigastric pain syndrome alone. In multivariate analysis, independent factors associated with all functional dyspepsia subtypes included worsening quality of life and the presence of symptoms compatible with functional heartburn and IBS, with functional heartburn and IBS having the strongest association with overlapping postprandial distress syndrome and epigastric pain syndrome. Notably, somatisation showed a positive association with postprandial distress syndrome and the overlapping variant, and use of antidepressants showed a negative association with postprandial distress syndrome. Interpretation: Approximately 10% of the adult population fulfils symptom-based criteria for Rome IV functional dyspepsia and incurs considerable associated health impairment. The functional dyspepsia subtypes show differing associations, suggesting differences in pathophysiological processes or influences. Funding: The Rome Foundation, the US National Institute of Diabetes and Digestive and Kidney Diseases, the Swedish Medical Research Council, AFA Insurance, Ferring Pharmaceuticals, and the Faculty of Medicine, University of Gothenburg, Gothenburg, Sweden