Irritable bowel syndrome (IBS) is a common chronic gastrointestinal disorder, with diarrhea-predominant IBS (IBS-D) as the most frequent subtype. The implication of gut microbiota in the disease's etiology is not fully understood. In vitro gut systems can offer a great alternative to in vivo assays in preclinical studies, but no model reproducing IBS-related dysbiotic microbiota has been developed. Thanks to a large literature review, a new Mucosal ARtifical COLon (M-ARCOL) adapted to IBS-D physicochemical and nutritional conditions was set-up. To validate the model and further exploit its potential in a mechanistic study, in vitro fermentations were performed using bioreactors inoculated with stools from healthy individuals (n = 4) or IBS-D patients (n = 4), when the M-ARCOL was set-up under healthy or IBS-D conditions. Setting IBS-D parameters in M-ARCOL inoculated with IBS-D stools maintained the key microbial features associated to the disease in vivo, validating the new system. In particular, compared to the healthy control, the IBS-D model was characterized by a decreased bacterial diversity, together with a lower abundance of Rikenellaceae and Prevotellaceae, but a higher level of Proteobacteria and Akkermansiaceae. Of interest, applying IBS-D parameters to healthy stools was not sufficient to trigger IBS-D dysbiosis and applying healthy parameters to IBS-D stools was not enough to restore microbial balance. This validated IBS-D colonic model can be used as a robust in vitro platform for studies focusing on gut microbes in the absence of the host, as well as for testing food and microbiota-related interventions aimed at personalized restoration of gut microbiota eubiosis.

We explored potential relationships between dietary live microbe intake and chronic diarrhea (CD) and fecal incontinence (FI).

We conducted a cross-sectional retrospective study based on the National Health and Nutrition Examination Survey (NHANES) database. Participants were categorized into three groups according to the Sanders classification system (low, medium, and high dietary live microbe groups). CD and FI were defined using a bowel health questionnaire. Logistic regression and restricted cubic spline (RCS) analyses were performed on weighted data to explore potential relationships.

In univariate logistic regression analyses, participants in the high dietary live microbe group exhibited a lower CD prevalence when compared to those in the low group (odds ratio (OR) = 0.58, 95% confidence interval (CI): 0.43-0.79). After adjusting for covariates, model 2 (OR = 0.69 95% CI: 0.49-0.96) and model 3 (OR = 0.66 95% CI: 0.45-0.96) data were consistent with model 1 data. No significant association was identified between dietary live microbe intake and FI. Withal, subgroup analyses revealed significant associations between high dietary live microbes and CD in males or participants without abdominal obesity, hypertension, diabetes, and sleep disorder (p < 0.05).

In this cross-sectional study, consuming foods rich in live microbes may exert positive effects on CD risk. This finding may facilitate new management strategies for CD.

Common gastrointestinal (GI) symptoms such as abdominal pain, indigestion, and constipation affect a significant portion of the global population and can substantially impair quality of life. Despite these widespread issues, research specifically investigating the effects of walnuts on gut function and GI symptoms remain limited.

This study investigates the effects of walnuts on gastrointestinal symptoms in healthy adults.

An experimental baseline-end study with an equivalent group design was employed.

The experimental group consumed 42 grams of walnuts daily, and their gastrointestinal symptoms were compared with those of a control group that did not consume walnuts over a 3-week period.

Sixty university students were recruited as volunteer subjects, consisting of 30 males and 30 females.

Participants were randomly assigned to either an experimental group or a control group.

The independent variable was walnut consumption, and the dependent variable was gastrointestinal health, assessed using the Gastrointestinal Symptom Rating Scale (GSRS) and a qualitative questionnaire to collect participants' perceived changes in GI symptoms.

A t-test with a p-value of less than 0.05 and verbatim analysis were utilized.

This mixed-methods study provides evidence for the beneficial effects of walnuts in promoting normal digestive function.

The study provides alternative evidence for the beneficial effects of walnuts in promoting normal digestive function.

In patients with disorders of gut-brain interaction (DGBI), overlapping non-gastrointestinal conditions such as fibromyalgia, headaches, gynaecological and urological conditions, sleep disturbances and fatigue are common, as is overlap among DGBI in different regions of the gastrointestinal tract. These overlaps strongly influence patient management and outcome. Shared pathophysiology could explain this scenario, but details are not fully understood. This overlap has been shown to be of great relevance for DGBI. In addition, symptoms considered to be caused by a DGBI could have a detectable organic cause, and in patients with a diagnosed organic gastrointestinal disease, symptoms not clearly explained by the pathology defining this organic disease are common. Thus, the aims of this Rome Foundation Working Team Report were to review the literature on overlapping conditions among patients with paediatric and adult DGBI and, based on the available epidemiological and clinical evidence, make recommendations for the current diagnostic and therapeutic approach, and for future research. Specifically, we focused on other DGBI in the same or different gastrointestinal anatomical region(s), DGBI overlap with organic bowel diseases in remission, and DGBI overlap with non-gastrointestinal, non-structural conditions.

Irritable bowel syndrome (IBS) is a frequent disorder thought to be caused by a disturbance of the gut-brain axis. Nutrition interventions are an essential pillar of its treatment. However, there is no consensus on which outcomes should be applied to assess the effectiveness of nutrition care in IBS. Standardized outcome sets, or "core outcome sets" (COS), have been proposed to harmonize outcomes in clinical research and practice. This project aims to develop a COS for dietitian-provided nutrition care in adults with IBS or food intolerances with intestinal symptoms, to be implemented in routine outpatient practice.

A comprehensive outcomes list was developed based on quantitative and qualitative studies, COS and guidelines on IBS, and important outcomes named by participants. Health service users, dietitians, gastroenterologists, and health care decision makers rated the outcomes in two Delphi survey rounds on their importance and ranked them in a third round. Data was analyzed by panel to account for the different views and sample sizes.

A total of 192 participants registered for the Delphi process. The following 14 outcomes reached consensus in all panels after two rounds: perception of symptom triggering foods/nutrients, intake of trigger foods/nutrients, practicability of diet, adherence, digestive symptoms overall, abdominal pain, abdominal bloating, stool consistency, stool frequency, physical functioning related QoL, nutrition related QoL, social functioning related QoL, empowerment of self-care.

The Delphi process yielded in a 14 outcomes COS, which exceeds what is typically considered feasible in routine nutrition care. Further work is needed to refine the COS and to identify standardized measurement tools for each outcome.

Mood disorders and disorders of gut-brain interaction (DGBI) are highly prevalent, commonly comorbid, and lack fully effective therapies. Although selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological treatments for these disorders, they may impart adverse effects, including anxiety, anhedonia, dysmotility, and, in children exposed in utero, an increased risk of cognitive, mood, and gastrointestinal disorders. SSRIs act systemically to block the serotonin reuptake transporter and enhance serotonergic signaling in the brain, intestinal epithelium, and enteric neurons. Yet, the compartments that mediate the therapeutic and adverse effects of SSRIs are unknown, as is whether gestational SSRI exposure directly contributes to human DGBI development.

We used transgenic, surgical, and pharmacological approaches to study the effects of intestinal epithelial serotonin reuptake transporter or serotonin on mood and gastrointestinal function, as well as relevant communication pathways. We also conducted a prospective birth cohort study to assess effects of gestational SSRI exposure on DGBI development.

Serotonin reuptake transporter ablation targeted to the intestinal epithelium promoted anxiolytic and antidepressive-like effects without causing adverse effects on the gastrointestinal tract or brain; conversely, epithelial serotonin synthesis inhibition increased anxiety and depression-like behaviors. Afferent vagal pathways were found to be conduits by which intestinal epithelial serotonin affects behavior. In utero SSRI exposure is a significant and specific risk factor for development of the DGBI, functional constipation, in the first year of life, irrespective of maternal depressive symptoms.

These findings provide fundamental insights into how the gastrointestinal tract modulates emotional behaviors, reveal a novel gut-targeted therapeutic approach for mood modulation, and suggest a new link in humans between in utero SSRI exposure and DGBI development.

A national research priority for people living with bile acid diarrhoea (BAD) is effective treatment options to improve their quality of life. This study aims to evaluate the feasibility of conducting a randomised controlled trial (RCT) of a novel healthy dietary pattern (The 8×5 Diet) to inform a future, larger trial.

We plan to enrol 76 UK adults living with BAD and ongoing diarrhoea using self-selection sampling and digital technologies. Eligible participants will be assigned to groups using permuted block randomisation using 1:1 allocation to receive either 8 weeks of usual care or The 8×5 Diet using one-to-one, dietitian counselling via a video-conferencing platform and developed digital resources. Randomisation, consent, recruitment, retention and acceptability will be evaluated using data from the RCT and post-trial interviews conducted with those in the intervention group. Secondary outcome exploratory assessment will include health-related quality of life, symptom relief, diarrhoea, diet quality, nutrient intakes and diet satisfaction.

Ethical approval was granted by the University of Manchester Research Ethics Committee (2024-19094-33261; V1.7, last updated: 24/02/2025).Findings will be disseminated through peer-reviewed publication, conference presentation and social media.

NCT06259396.

Low-dose amitriptyline, a tricyclic antidepressant (TCA), was superior to placebo for irritable bowel syndrome (IBS) in the AmitripTyline at Low-dose ANd Titrated for Irritable bowel syndrome as Second-line treatment (ATLANTIS) trial.

To perform post hoc analyses of ATLANTIS for predictors of response to, and tolerability of, a TCA.

ATLANTIS randomised 463 adults with IBS to amitriptyline (232) or placebo (231). We examined the effect of baseline demographic and disease-related patient characteristics on response to amitriptyline and the effect of amitriptyline on individual symptoms and side effects by subtype.

There was a quantitative difference in amitriptyline effectiveness in those ≥50 years vs <50 on the IBS severity scoring system (IBS-SSS) (interaction p=0.048, mean difference in ≥50 years subgroup -46.5; 95% CI -74.2 to -18.8, p=0.0010), and subjective global assessment of relief (interaction p=0.068, OR in ≥50 years subgroup 2.59; 95% CI 1.47 to 4.55, p=0.0010), and those in the 70% most deprived areas of England compared with the 30% least deprived for a ≥30% improvement in abdominal pain (interaction p=0.021, OR in 70% most deprived subgroup 2.70; 95% CI 1.52 to 4.77, p=0.0007). Stronger treatment effects were seen in men, with higher Patient Health Questionnaire-12 scores, and with IBS with diarrhoea. Mean differences in individual IBS-SSS components favoured amitriptyline, and side effects were similar, across almost all IBS subtypes.

These exploratory analyses demonstrate there are unlikely to be deleterious effects of amitriptyline in any particular IBS subtype and could help identify patients in whom amitriptyline may be more effective.

ISRCTN48075063.

The pathophysiology of irritable bowel syndrome (IBS) and masked hypertension (mHT) exhibits shared characteristics, including factors such as anxiety and stress. Consequently, the aim of this study was to investigate the frequency of mHT in patients with IBS.

Patients diagnosed with IBS in 2020-2023 were re-evaluated using the Rome IV criteria. Patients who did not have sustained HT, as evidenced by repeated in-office blood pressure (BP) measurements and who did not meet the exclusion criteria (chronic renal failure, heart failure, diabetes, cerebrovascular events, pregnancy or puerperium) were included in the study group. A control group was also constituted with the same number of age and gender-matched healthy individuals. The participants were connected to a 24-hour ambulatory BP monitor and the results were analyzed.

Total 128 participants, including 64 IBS patients and 64 healthy individuals, were included in our study. The age (36.9 ± 7.3 years; 37.3 ± 7.7 years) and gender (62.5% female; 62.5% female) distributions and the baseline clinical characteristics of the study and control groups were similar. The in-office systolic BP measurements of the IBS patients were significantly higher than those of the control group (124.7 ± 5.4 mmHg compared to 121.8 ± 5.2 mmHg, p = 0.02). The IBS patients also had a higher frequency of mHT (n = 21, 32.8% compared to n = 10, 15.6%, p = 0.02), higher 24-hour daytime systolic BP (127.5 ± 7.6 mmHg compared to 124.8 ± 5.22 mmHg, p = 0.02) and higher nighttime diastolic BP (62.2 ± 7.5 mmHg compared to 59.6 ± 6.1 mmHg, p = 0.03) than the control group. The study group included all four sub-types of IBS: diarrhea-dominant (IBS-D), constipation-dominant (IBS-C), mixed type (IBS-M) and unclassified (IBS-U). It was determined that 57.9% of the IBS-C patients, 27.8% of the IBS-M patients, 23.5% of the IBS-D patients and 10% of the IBS-U patients in the study group had mHT.

To the best of our knowledge, this is the first study demonstrating a relationship between IBS and mHT. The frequency of mHT was higher among patients with IBS compared to healthy controls (p = 0.02). Studies on larger patient groups are needed to evaluate the frequency of mHT for the IBS sub-types.

To describe the protocol used for translation and cross-cultural adaptation of the questionnaires developed by the Rome Foundation for the diagnosis of disorders of gut-brain interaction in the pediatric population.

The protocol was proposed based on a narrative review of the literature on the cultural adaptation process of measurement instruments in epidemiology, analyzing its stages, and verifying its use and feasibility. The guidelines for the cross-cultural adaptation of diagnostic instruments developed by the Rome Foundation, which defines and periodically reviews diagnostic criteria, were incorporated into the protocol.

The proposed protocol includes: (i) preparation; (ii) forward translation; (iii) reconciliation; (iv) backward translation; (v) review of the backward translation; (vi) cognitive debriefing; (vii) final review; (viii) calculation of the item content validity index; and (ix) approval by the Rome Foundation.

The methodological steps described in this protocol may contribute to future translations and cross-cultural adaptations of diagnostic questionnaires of disorders of gut-brain interaction and other materials from the Rome Foundation, enabling their use in epidemiological studies.

The frequency of anal incontinence in the general population is likely an underestimation, particularly among adults ≤65 years, for whom personal and professional considerations limit their utilization of medical care. The objective of this study was to assess the prevalence of anal incontinence in the young population and to address the reasons why such individuals do not seek care.

This was a public health survey conducted using personal and professional social networks between April and November 2023. Participants between the ages of 18 and 65 were invited to respond a survey about their experience of anal incontinence (AI). The survey collected data on the Vaizey's score and the Anal Incontinence Quality of Life Index (FIQL).

Of the 481 individuals who completed the survey, 176 (36.6 %) reported experiencing AI. The majority of respondents exhibited mild incontinence (46 %), while 15.8 % experienced severe or major AI. Among those with AI, only 27.3 % consulted a physician, and in nearly 40 % of cases, no treatment was proposed. The primary reasons for not seeking consultation were embarrassment about the condition (63 %) and perceived stigma surrounding treatment (28 %), including a lack of awareness about available treatments. Multivariate analysis revealed that individuals between the ages of 26 and 45 were more likely to seek medical attention.

The prevalence of incontinence of the anal nature among young adults remains significantly underestimated, despite its impact on their quality of life. Enhanced public health communication regarding the management of incontinence, particularly among young individuals and healthcare providers, is imperative.

Gastrointestinal disorders (GIDs) in the elderly often lead to impaired gastric motility and nutrient absorption, exacerbating malnutrition. Probiotics, particularly Lactobacillus rhamnosus GG (LGG), may enhance gastric motility and nutrient absorption. This study evaluates the impact of LGG supplementation on gastric motility and nutrient absorption in elderly patients with GIDs.

A retrospective analysis was conducted on 231 elderly patients with GIDs, divided into a probiotic supplementation (PS) group (n = 110) and a NPS group (n = 121). The PS group received LGG (1 × 1010 CFU, twice daily) for at least 7 days. Baseline and post-treatment measurements included gastric motility via ultrasonography, gastrointestinal hormone levels using radioimmunoassay, and nutrient absorption markers through ELISA and calorimetry.

Post-treatment, the PS group exhibited significantly improved gastric motility, with increased antral contraction amplitude (58.65 mm vs. 56.53 mm; P = 0.004), frequency (4.06 vs. 3.81 times/min; P = 0.009), and reduced gastric half-emptying time (28.15 min vs. 29.77 min; P = 0.007). Hormone analyses showed elevated motilin and neuropeptide Y levels and decreased vasoactive intestinal peptide levels in the PS group (P < 0.05). Nutrient absorption markers indicated decreased stool fat, protein, and carbohydrate content, enhanced intestinal permeability, increased weight and digestibility of energy, fat, and protein in the PS group (P < 0.05).

PS with LGG significantly enhances gastric motility and nutrient absorption in elderly patients with GIDs, indicating potential therapeutic benefits for addressing digestive dysfunction and malnutrition in this demographic.

To explore the association between CEN and GIDs, and elucidated the potential role of circulating protein biomarkers.

The study utilized UK Biobank data from 156,686 participants, with data collection occurring between March 13, 2006 and October 1, 2010. Participants with GIDs at baseline were excluded from further analysis. CEN data were obtained from the baseline assessments. Differential protein analyses were conducted using OLINK data. GIDs and their subclasses were identified through electronic health records. Cox proportional hazards regression models were employed to assess the association between CEN and the risk of GIDs, along with sensitivity and multidimensional stratification analyses. Additionally, mediation analysis was performed to explore the role of differential protein biomarkers.

The results indicated that the mild CEN (CENmild) group was associated with a significantly lower risk of various GIDs than the severe CEN (CENsevere) group, including overall GIDs (HR = 0.78,95%CI:0.74-0.81) and peptic ulcers (HR = 0.37,95%CI:0.20-0.68). OLINK differential analysis revealed that APOF expression was significantly higher in the CENmild group compared to the CENsevere group (PAPOF = 7.09E-08,FC = 0.048), whereas other differential protein expression (PBPIFB2 = 8.93E-06,FC = -0.122;PFABP4 = 3.19E-06,FC = -0.101;PGGH = 4.58E-07,FC = -0.054;PLEP = 5.39E-08,FC = -0.195) was significantly lower in the CENsevere group. Cox regression analysis showed that higher APOF expression was associated with a reduced risk of multiple GIDs, while the expression of other differential proteins increased the risk of corresponding GIDs. Mediation analysis indicated that these proteins mediated 0.5 % to 6.7 % of the CEN-GIDs association.

In this cohort study, CEN was significantly associated with a higher risk of GIDs in the adulthood, and circulating protein biomarkers partially mediated the associations.

Diagnosing pediatric patients with chronic gastroduodenal symptoms is clinically challenging, with the role of gastric emptying testing being controversial. Body Surface Gastric Mapping (BSGM) is a new diagnostic test that can identify specific patient phenotypes in adults with gastric dysfunction. This study evaluates whether BSGM can delineate specific phenotypes in adolescents and provide clinically meaningful distinctions between gastroparesis and functional dyspepsia diagnoses.

A prospective cross-sectional study recruited adolescents aged 12 to 21 between 2022 and 2024. Controls were recruited from New Zealand and patients from the Children's Hospital of Philadelphia, USA. BSGM followed a standardized protocol, including simultaneous symptom reporting and completion of validated symptom, psychometric, and physical health questionnaires.

Fifty-six subjects were recruited (31 controls, 25 patients); median age 16; 96% of patients were female. Control data showed that adult reference intervals provided an acceptable interpretation framework. Patients with FD (n = 10) and gastroparesis (n = 15) had common symptoms, mental health, quality of life, and functional disability (all p > 0.05). Three distinct BSGM phenotypes were identified: BSGM Normal (n = 10), BSGM Delay (n = 8), and Low Stability/Low Amplitude (n = 7), having spectral differences in BMI-Adjusted Amplitude 34.6 versus 39.1 versus 19.9 (p = 0.01) and Gastric Alimetry Rhythm Index: 0.45 versus 0.45 versus 0.19 (p = 0.003). BSGM phenotypes demonstrated differences in symptoms (nausea p = 0.04), physical health (p = 0.04), and psychometrics (anxiety p = 0.03).

Adolescents with FD and gastroparesis have overlapping clinical profiles, making treatment challenging. Conversely, employing BSGM to categorize patients into distinct phenotypes reveals clinically relevant differences, offering avenues for individualized therapeutic pathways.

Background: While the low fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet, low FODMAP diet (LFD) has demonstrated effectiveness in managing irritable bowel syndrome (IBS) symptoms, little is known about sex-specific responses to this dietary intervention. Aim: This study evaluates the role of sex differences in symptom improvement following a dietitian-led, group education session on the LFD for IBS patients. Methods: A total of 305 patients, including 249 with a diagnosis of IBS and 56 classified as having suspected IBS, were enrolled in this study (79.7% female). Patients attended two group education sessions on the LFD. Primary outcomes were measured using the IBS Symptom Severity Score (IBS-SSS) and the Global Symptom Question (GSQ). Secondary outcomes included stool frequency, stool consistency and individual symptoms assessed by the Gastrointestinal Symptom Rating Scale. Statistical analyses were performed to compare baseline and follow-up data within and between sexes. Results: Both male and female patients experienced significant reductions in IBS-SSS scores and improvements in GSQ satisfactory relief, stool frequency, stool consistency and individual gastrointestinal (GI) symptoms following the LFD (p < 0.05). There were no significant between-sex differences in the extent of symptom relief (p > 0.05). Conclusion: The study found no significant sex-based differences in symptom reduction or GI relief following the intervention. These findings suggest that, despite differing symptom profiles and IBS prevalence, both male and female patients achieve similar relief with the LFD group education.

Abdominal pain in constipation-predominant irritable bowel syndrome (IBS-C) and functional constipation (FC) remains a difficult clinical challenge due to unclear pathophysiological mechanisms and limited pain-targeted treatments. This review critically evaluates the evidence on the underlying pain mechanisms in IBS-C and/or FC and explores management strategies, their limitations, and future directions.

Most research on constipation-related pain is based on IBS-C patients or animal models, with limited studies focusing on FC. Visceral hypersensitivity, serotonin dysregulation, gut-brain axis dysfunction, and central/peripheral nervous system alterations are implicated in IBS-C pain, while FC pain is less studied and may be primarily linked to colonic distension and motility dysfunction. Management strategies include 5-HT4 agonists, GC-C agonists, chloride channel activators, psychological therapies, probiotics and complementary medicine. Despite available treatment options, managing abdominal pain in IBS-C and FC remains challenging due to heterogeneous pathophysiology and limited targeted therapies. While some interventions provide symptomatic relief, there is no universally effective treatment for abdominal pain across all patients. Future research should focus on identifying pain-specific biomarkers, refining diagnostic criteria, and integrating multi-omics data and neuroimaging techniques to better distinguish pain mechanisms in IBS-C versus FC and develop more precise, patient-centered interventions.

Linaclotide is effective in relieving constipation-predominant irritable bowel syndrome symptoms. However, few studies focus on the efficacy of linaclotide for overlapping symptoms of functional dyspepsia among irritable bowel syndrome patients. This study aimed to assess the efficacy of linaclotide compared with lactulose in patients with functional dyspepsia and constipation-predominant irritable bowel syndrome overlap.

Seventy-eight patient were randomized (2:1) to receive linaclotide 290 μg or lactulose 20 mL daily for 4 weeks. The primary endpoint was the overall treatment satisfaction for gastrointestinal symptom relief. The secondary endpoints included score changes in functional dyspepsia, constipation-predominant irritable bowel syndrome symptoms, and psychological status.

Seventy-one patients (47 with linaclotide and 24 with lactulose) completed the study. A higher proportion of patients receiving linaclotide reported partial or complete relief of gastrointestinal symptoms compared with patients receiving lactulose (87.2% vs. 54.2%, p = 0.002). Dyspeptic symptoms (postprandial fullness/early satiety and bloating) and bowel symptoms (stool frequency, consistency, straining, sensation of complete evacuation, and lower abdominal discomfort) showed greater improvement in linaclotide-treated patients than in lactulose group (p < 0.05).

Linaclotide shows better efficacy for functional dyspepsia and constipation-predominant irritable bowel syndrome overlap compared with lactulose.

ClinicalTrials.gov: NCT05134584.

Zuojin Pill (ZJP) is a traditional Chinese medicine (TCM) formula composed of Coptidis Rhizoma and Euodiae Fructus in a ratio of 6:1 (w/w), which has been widely used for treating gastrointestinal disorders, especially stomach heat syndrome (SHS). However, the active alkaloids in ZJP showed low plasma exposure in rats following oral administration, which failed to explain their potent pharmacological effects, thereby limiting further mechanism studies.

This study aimed to investigate the in vivo exposure and tissue distribution propensities of the active alkaloids in normal and SHS rats following oral administration of ZJP.

A rat model of SHS was induced by oral administration of chili pepper decoction and anhydrous ethanol. Then, the plasma and tissue pharmacokinetics of active alkaloids, including four protoberberine alkaloids (PBAs) and three indole alkaloids (IDAs), were investigated following oral administration of ZJP. Furthermore, desorption electrospray ionization mass spectrometry imaging (DESI-MSI) was employed to characterize the spatial distribution of active alkaloids in the stomach and liver. Western blot and immunofluorescence were employed to evaluate the gastric mucosal barrier integrity.

Based on the tissue-to-plasma partition coefficient (Kp) values, the in vivo exposure levels of berberine (BBR), palmatine (PAL), coptisine (COP), and dehydroevodiamine (DHE) were found to be higher in tissues than in plasma, indicating a distinct tissue distribution propensity. Each alkaloid displayed the highest exposure in the gastrointestinal tissues, due to local penetration facilitated by its direct contact with the mucosal lining. Pathological states reduced the overall exposure of PBAs in the gastric mucosa. In non-gastrointestinal tissues, most alkaloids, especially BBR and COP, exhibited a potent liver distribution propensity with minimal impact from pathological states. According to DESI-MSI results, PBAs showed high exposure in the damaged regions of gastric mucosa, which was attributed to mucosal barrier damage and enhanced permeability. In the liver, PBAs were primarily localized in the parenchyma surrounding the central vein and portal area.

This study demonstrated the stomach and liver distribution propensity of the active alkaloids in ZJP, providing a scientific basis for these alkaloids as the pharmacodynamic material basis of ZJP against SHS from the perspective of drug exposure.

Enteric infections often cause long-term sequelae, including persistent gastrointestinal symptoms, such as pain, discomfort, or irritable bowel syndrome. The plethora of sensory symptoms indicates that gut-innervating neurons might be directly affected by inflammation. However, sequencing studies of neurons in the gastrointestinal tract are hampered by difficulties in purifying neurons, especially during inflammation. Activating a nuclear GFP tag selectively in neurons enabled sort purification of intrinsic and extrinsic neurons of the gastrointestinal tract in models of intestinal inflammation. Using bulk and single-nucleus RNA sequencing, we mapped the whole transcriptomic landscape and identified a conserved neuronal response to inflammation, which included the interferon signaling and ferroptosis pathway. Deletion of the interferon receptor 1 in neurons regulated ferroptosis, neuronal loss, and consequently gut-transit time. Collectively, this study offers a resource documenting neuronal adaptation to inflammatory conditions and exposes the interferon and ferroptosis pathways as signaling cascades activated in neurons during inflammation.

Gastrointestinal (GI) symptoms are common and can affect children's social lives. This study investigated the effects of exposure to a rich natural environment on GI symptoms, salivary cortisol levels, salivary amylase levels, and the gut microbiota in young children. Children aged 5-6 years from four kindergartens in Japan were randomly assigned to two groups: a nature childcare group and a regular childcare group. The children were exposed to their respective conditions once weekly for one month. Before and after the intervention, GI symptoms were detected using the Children's Somatization Inventory to calculate a 'GI score' and categorize participants into GI and control groups (primary outcome measure). Fecal examinations were performed for gut microbiota using 16 S-rRNA analysis, salivary cortisol and amylase levels were quantified, and the Child Behavior Checklist was administered. The two groups had similar GI symptoms, salivary cortisol and amylase levels, and behavioral characteristics. Following the intervention, significant differences in the GI score, abdominal pain, constipation, Shannon index value, and salivary cortisol and amylase levels (p < 0.05) were observed between the two childcare groups. Spending free and abundant time in nature during early childhood could help maintain digestive system homeostasis, increase gut microbiota diversity, and reduce cortisol levels.

Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction, with a multifactorial pathophysiology involving gut-brain axis dysregulation, visceral hypersensitivity, microbiota imbalance, and immune dysfunction. Traditional IBS management emphasizes dietary modifications and pharmacologic therapies. However, increasing attention has been directed toward functional foods, nutraceuticals, and herbal remedies due to their potential to target IBS pathophysiological mechanisms with favorable safety profiles. This clinical review explores the role of these adjunctive therapies, evaluating evidence from preclinical and clinical studies. Functional foods such as kiwifruit, prunes, and rye bread demonstrate benefits in bowel habit regulation through fiber content and microbiota modulation. Nutraceuticals like peppermint oil, palmitoylethanolamide, and herbal mixtures exhibit anti-inflammatory, antispasmodic, and analgesic effects. Prebiotics provide substrate-driven microbiota changes, although dosage is key, as given their fermentative properties, when used at high dosages, they can exacerbate symptoms in some individuals. Probiotics and postbiotics offer microbiota-based interventions with promising symptom relief in IBS subtypes, although factors for personalized treatment still need to be further elucidated. These strategies highlight a paradigm shift in IBS management, integrating diet-based therapies with evolving nutraceutical options to improve patient outcomes. Despite promising findings, challenges in standardizing definitions, mechanisms, and safety profiles still remain. Rigorous, large-scale trials to validate the therapeutic potential of these interventions are needed, to enhance the benefits of these compounds with an individualized treatment approach.

Background: Irritable Bowel Syndrome (IBS) is a complex disorder characterized by altered gut-brain interactions, with gastrointestinal microbiota and metabolic dysregulation playing key roles in its pathophysiology. Identifying specific metabolic alterations within the colonic mucosa may enhance our understanding of IBS and contribute to improved diagnostic and therapeutic approaches. Methods: This cross-sectional study analyzed the metabolomic profiles of colonic mucosal biopsies from 44 IBS patients assessed with ROME IV criteria and 69 healthy controls undergoing colonoscopy. Untargeted metabolomic profiling was conducted using liquid chromatography-mass spectrometry (LC-MS), and differential metabolite analysis was performed via fold-change calculations and machine learning-based classification. Results: IBS patients exhibited distinct mucosal metabolic profiles, with significantly elevated levels of N-acetylneuraminic acid and 1-palmitoylglycerol, suggesting compromised epithelial integrity and increased gut permeability. In contrast, cis-4-hydroxycyclohexanecarboxylic acid, a metabolite associated with protective mucosal functions, was reduced. Random Forest analysis identified these metabolites as key discriminatory features between IBS and control groups, reinforcing their potential role as biomarkers for IBS-related mucosal alterations. Conclusions: Our study highlights the unique metabolomic signatures of IBS at the mucosal level, emphasizing the role of microbial metabolites in disease pathology. These findings may facilitate the development of novel diagnostic tools and targeted therapeutic strategies, advancing personalized management for IBS patients.

Obesity has emerged as a major public health concern worldwide. However, the relationship between obesity and irritable bowel syndrome (IBS) remains unclear.

We aimed to systematically examine the association of both general and central obesity measures with risk of incident IBS in a large population-based cohort.

Participants free of IBS, celiac disease, inflammatory bowel disease, and any cancer at baseline were included. Obesity was assessed using various measures of general and central obesity [i.e., Body mass index (BMI in kg/m2), waist circumference, etc.]. The primary outcome was incident IBS. The Cox proportional hazard model was conducted to estimate the association.

Among 416,124 participants (mean age 56.2 y), 133,775 (32.1%), 178,283 (42.8%) and 102,139 (24.5%) were BMI-defined normal, overweight and obesity at baseline. During a median of 14.6-y follow-up, 8744 (2.1%) incident IBS were identified. After multiple adjustments, individuals with obesity had a 7% higher risk of developing IBS than those with normal BMI [hazard ratio (HR): 1.07; 95% confidence interval (CI): 1.01, 1.13]. As for central obesity, individuals with the highest quartiles of waist circumference (HR: 1.14; 95% CI: 1.06, 1.27) and visceral adipose tissue volume (HR: 1.35; 95% CI: 1.04, 1.75) had a 14% and 35% greater risk of IBS compared with the lowest quartiles. A similar positive association was observed in other general and central obesity measures, with an 8-35% higher risk of IBS occurrence in the highest quartile compared with the reference group. Further sensitivity analyses and subgroup analyses demonstrated similar results.

Both general and central obesity are associated with an increased risk of developing IBS, suggesting the importance of obesity management.

Past studies have shown a substantial overlap between irritable bowel syndrome (IBS) and gastroesophageal reflux disease (GERD). This study investigated the prevalence of DCPR-revised (DCPR-R) syndromes in patients with IBS alone and those with overlapping IBS-GERD. We also explored the relationship of these syndromes with various psychological scales.

In total, 341 patients from the Chinese IBS cohort completed the GerdQ scale and a series of psychological questionnaires. Semi-structured interviews were conducted to evaluate DCPR-R, as well as scores on the Psychosocial Index (PSI), Psychosomatic Symptom Scale (PSSS), World Health Organization (WHO)-5 Well-being Index, Euthymia Scale, Patient Health Questionnaire-9, and 7-item Generalized Anxiety Disorder Scale.

Compared with patients with IBS alone, patients with overlapping IBS-GERD had a significantly higher prevalence of DCPR-R syndromes, particularly in areas such as demoralization, persistent somatization, despair-related demoralization, hypochondriasis, disease phobia, anniversary reaction, thanatophobia, and conversion symptoms. Patients with two or more types of DCPR-R syndromes were more likely to exhibit psychological disorders. In patients with IBS alone, the WHO-5 Well-being Index and PSI well-being scores were predictive of two or more DCPR-R syndromes. For patients with overlapping IBS-GERD, the PSSS score was an independent predictor.

This study highlights key differences in psychosomatic factors between patients with IBS alone and those with overlapping IBS-GERD. The DCPR-R syndromes and various psychological scales offer valuable tools for diagnosing and assessing these differences.

Gastroesophageal reflux disease (GERD) and flatulence are both prevalent afflictions and negatively impact the quality of life. This study aims to determine the relationship between the Global Diet Quality Score (GDQS), a novel metric based on the Prime Diet Quality Score with GERD and flatulence in Iranian adults.

The cross-sectional study was conducted among 6202 adults in the context of the Shahedieh cohort study accomplished. Dietary intakes of participants were collected by food frequency questionnaires (FFQs). To calculate GDQS, 25 food groups were comprised (16 healthy and 7 unhealthy food groups and two food groups categorized as unhealthy when consumed excessively). GERD and flatulence were assessed by a self-reported questionnaire. To examine the association between GDQS with GERD and flatulence, logistic regression was performed in crude and adjusted models (Model I: adjustments for age and energy intake; Model II: gender, physical activity, marital status, occupation, educational levels, WSI, and BMI; and Model III: smoking status, depression, diabetes, hypertension, and cardio events.) RESULTS: Participants in the highest quintile of GDQS had 20% higher odds of having GERD than individuals in the lowest one (OR: 1.20; 95% CI: 0.88-1.65, P trend = 0.508). Compared to the lowest quintile, the participants in the highest quintile had no significant reduction in probability of having flatulence in the crude model (OR: 0.94; 95% CI: 0.81-1.11, P trend = 0.578). These associations remained non-significant after adjustments for confounding variables.

No significant associations were observed between higher adherence to GDQS with odds of GERD and flatulence in Iranian adults. To better understand these findings, longitudinal studies especially randomized clinical trials are needed.

CD146 plays a key role in cancer progression and metastasis. Cancer stem cells (CSCs) are responsible for tumor initiation, drug resistance, metastasis, and recurrence. In this study, we explored the role of CD146 in the regulation of liver CSCs. Here, we demonstrated that CD146 was highly expressed in liver CSCs. CD146 overexpression promoted the self-renewal ability and chemoresistance of Hepatocellular Carcinoma (HCC) cells in vitro and tumorigenicity in vivo. Inversely, knockdown of CD146 restrained these abilities. Mechanistically, CD146 activated the NF-κB signaling to up-regulate JAG2 expression and activated the Notch signaling, which resulted in increased stemness of HCC. Furthermore, JAG2 overexpression restored the Notch signaling activity, the stemness, and chemotherapeutic resistance caused by CD146 knockdown. These results demonstrated that CD146 positively regulates HCC stemness by activating the JAG2-NOTCH signaling. Combined targeting of CD146 and JAG2 may represent a novel therapeutic strategy for HCC treatment.

Cannabis use in the general population is prevalent and is rising because of increased acceptance of its use, legalization in most US states, and perceived health benefits. Cannabis product potency has dramatically increased with higher delta-9-tetrahydrocannabinol content. Cannabis has documented antiemetic properties and cannabinoid pharmaceuticals are used in disorders like chemotherapy-induced nausea and vomiting.

Forty to eighty percent of cyclic vomiting syndrome (CVS) patients use cannabis products, which reportedly reduce stress as well as nausea and vomiting. Cannabinoid hyperemesis syndrome (CHS) has a presentation similar to CVS, but is associated with longstanding, high dose cannabis use, and is thought to be relieved by sustained cannabis abstinence. Most CHS patients have used cannabis on a daily or near-daily basis for more than 2 years. Compulsive hot-water bathing behaviors are reported by most CHS patients, but are not specific for this disorder as they are also noted by about half of CVS patients. Episodic vomiting associated with cannabis use contributes to extensive health resource use, including emergency department visits and inpatient hospitalizations, and impacts patients and their families negatively. Treatment for CHS overlaps with CVS although cannabis abstinence remains the cornerstone of its management. Challenges associated with cannabis use cessation in CHS include patient skepticism of the role of cannabis as a cause of symptoms, perceived benefits of cannabis, and a lack of other effective therapies. In this review, we highlight cannabis use patterns in the US and discuss diagnosis and management of CHS and gaps in knowledge about this disorder.

Comorbidity with other conditions is common in functional bowel disorders. We aimed to investigate the prescription patterns of commonly used drugs in patients with irritable bowel syndrome (IBS) and functional unspecific bowel disorder, compared to the general population.

Prescriptions of commonly used drugs in 2022 were compared between patients and the general population from the same age group and region in Sweden.

Of 526 patients, 317 were followed up in 2022 (219 women and 98 men) and were compared to 51,001 women and 55,571 men in the general population. The median follow-up time from the first visit to 2022 was 8 years (25th-75th percentile 6-11 years). Female patients were significantly more likely than controls to be prescribed PPIs, antibiotics, NSAIDs, paracetamol, opioids, muscle relaxants, antimigraine drugs, antidepressants and asthma medications. Male patients were significantly more likely than controls to be prescribed PPIs, opioids, antidepressants, and asthma medications. In the year prior diagnosis and through 2022, female patients showed a significant decline in the use of PPIs (38% vs.10%; p < 0.001), antibiotics (27.5% vs. 20.1%; p = 0.0426), NSAIDs (23.3% vs.14.6%; p = 0.012), opioids (20.6% vs. 7.5%; p < 0.001), and a significantly increase in the use of asthma medications (15.5% vs. 24.2%; p = 0.0088). Male patients showed a significant decline in the use of PPIs and NSAIDs.

Patients with functional bowel disorders are more likely to be prescribed medications for conditions other than IBS. Over time, there was a decline in the prescriptions of most drugs, except for antidepressants and asthma medications.

Whether pathophysiological factors differ between males and females with irritable bowel syndrome-diarrhea (IBS-D) remains to be tested. To better understand potential sex differences, males with IBS-D were compared to naturally cycling females and to females with IBS-D taking hormonal contraception on plasma levels of cytokines and gut microbiome characteristics.

Males and females with Rome III IBS-D completed questionnaires and kept a daily symptom diary for 28 days. Blood and stool samples were collected between days 3 and 8 of the daily diary (estrogen-dominant days in naturally cycling females). Blood samples were analyzed for lipopolysaccharide (LPS)-stimulated and unstimulated cytokine levels. Stool samples were analyzed for microbiota signatures using 16S rRNA sequencing.

Forty-seven participants with IBS-D (13 males, 22 naturally cycling females, 12 females with hormonal contraception use) ages 18 to 50 years were studied. Males had similar unstimulated IL10, IL12P40, IL12P70, IL1β, IL8, and TNFα plasma cytokine levels compared to naturally cycling females, but higher levels compared with females using hormonal contraception. LPS-stimulated IL12P70 levels were lower in both groups of females vs. males. Alpha- and beta-diversity did not differ although differences in genus-level bacteria were found.

Cytokine levels differed between males and females using hormonal contraceptives but not between males and normally cycling females. It is important to consider that naturally cycling females may have a different cytokine and microbiome profile than females using hormonal contraceptives. Whether this portends a sex difference in potential etiologic factors remains to be determined.

Disorders of gut-brain interaction, such as functional dyspepsia (FD), are prevalent and challenging conditions. In other gastrointestinal (GI) disorders, individuals from underserved areas (UAs) have difficulty accessing care. Little is known about UA FD patient perspectives of their care, especially in those with limited English proficiency. We aimed to characterize patients' experiences with FD management with the goal of informing future studies targeting disorders of gut-brain interaction management in potentially vulnerable communities residing in UAs.

Participants meeting FD criteria were identified in 2 community health centers affiliated with a large academic medical center in the Northeastern United States. Semistructured interviews were conducted in English and Spanish. Transcripts were reviewed by a bilingual panel of investigators using the constant comparative method of iterative data acquisition. Psychosocial stressors and GI symptom severity were assessed.

A total of 26 participants were interviewed (12 English-speaking and 14 Spanish-speaking). Broadly, GI symptoms were mild and there was mild-to-moderate psychological distress present. Adverse social determinants of health were highly prevalent. Despite mild symptom severity on objective scales, FD severely affected quality of life and interfered with physical, psychological, and social well-being, including avoidance of certain foods and professional/social situations. Study participants (particularly those with limited English proficiency status) reported difficulty in receiving care. Thematic saturation was achieved.

Even when symptoms were mild, interviewees from UAs reported significant FD-related impairment, along with psychological distress. Education interventions targeting FD-related care in UAs should be designed to improve shared decision making in FD, sensitive to the burden of social determinants of health.

We aimed to examine the prospective association of sugar-sweetened beverages (SSB), artificially sweetened beverages (ASB), natural juice, and sugar forms with irritable bowel syndrome (IBS). Participants free of IBS, celiac disease, inflammatory bowel disease, and any cancer at recruitment were included (N = 178,711, 53.1% female). SSB, ASB, natural juice, and different sugar forms' consumption were measured via a 24-h dietary recall questionnaire. The primary outcome was incident IBS. A Cox proportional hazard model adjusting for age, sex, BMI, Townsend deprivation index, education, ethnicity, smoking, alcohol drinking, physical activity, total energy intake, type 2 diabetes, depression, and anxiety was conducted to assess the relationship. Mean consumption of SSB, ASB, and natural juice was 90.0, 72.4, and 105.7 g/day, respectively. During a median of 11.3-year follow-up, 2690 participants developed IBS. Every 100 g/day SSB increment was associated with a 3% higher IBS risk (HR = 1.03, 95% CI: 1.01-1.05). Compared with no SSB intake, the highest quartile was associated with an increased risk of IBS (HR = 1.19, 1.03-1.37; p trend = 0.017). Regarding ASB and natural juice, no significant association was detected in those who consumed the highest quartile versus no intake (ASB: HRQ4 VS no intake = 1.12, 0.95-1.31, p trend = 0.062; Natural juice: HRQ4 VS no intake = 1.01, 0.87-1.18, p trend = 0.363). Considering different sugar forms, increased IBS risk was detected in added sugar (HRQ4 VS Q1 = 1.20, 1.05-1.36, p trend = 0.001), instead of naturally occurring sugar (HRQ4 VS Q1 = 0.99, 0.88-1.11, p trend = 0.869). Higher intake of SSB, rather than ASB and natural juice, is associated with increased IBS risk. Higher consumption of added sugar, instead of naturally occurring sugar, is associated with higher IBS risk. These findings highlight the importance of limiting SSB consumption in diets to reduce the modifiable burden of IBS.

Disorders of Gut-Brain Interaction (DGBI) are widely prevalent and commonly encountered in gastroenterology practice. While several peripheral and central mechanisms have been implicated in the pathogenesis of DGBI, a recent body of work suggests an important role for the gut microbiome. In this review, we highlight how gut microbiota and their metabolites affect physiologic changes underlying symptoms in DGBI, with a particular focus on their mechanistic influence on GI transit, visceral sensitivity, intestinal barrier function and secretion, and CNS processing. This review emphasizes the complexity of local and distant effects of microbial metabolites on physiological function, influenced by factors such as metabolite concentration, duration of metabolite exposure, receptor location, host genetics, and underlying disease state. Large-scale in vitro work has elucidated interactions between host receptors and the microbial metabolome but there is a need for future research to integrate such preclinical findings with clinical studies. The development of novel, targeted therapeutic strategies for DGBI hinges on a deeper understanding of these metabolite-host interactions, offering exciting possibilities for the future of treatment of DGBI.

Changes in the composition of the gut microbiota have been associated with the development of irritable bowel syndrome (IBS). However, to what extent specific bacterial species relate to clinical symptoms remains poorly characterized. We investigated the clinical relevance of bacterial species linked with increased proteolytic activity, histamine production, and superantigen (SAg) production in patients with IBS.

Fecal (n = 309) and nasal (n = 214) samples were collected from patients with IBS and healthy volunteers (HV). Clinical symptoms and gut transit time were evaluated. Bacterial abundance in feces and nasal swabs as well as fecal trypsin-like activity were assessed.

The percentage of fecal samples containing Staphylococcus aureus was significantly higher in IBS compared with HV. Forty-nine percent of S. aureus -positive fecal samples from patients with IBS were also positive for SAgs, compared with 12% of HV. Patients with IBS and positive fecal SAg-producing S. aureus reported higher pain scores than those without S. aureus . Moreover, increased fecal proteolytic activity was associated with abdominal pain. Fecal abundance of Paraprevotella clara and Alistipes putredinis was significantly decreased in IBS, particularly in samples with higher proteolytic activity. Patients with lower Alistipes putredinis or Faecalibacterium prausnitzii abundance reported more severe abdominal pain.

In keeping with our preclinical findings, we show that increased presence of SAg-producing S. aureus in fecal samples of patients with IBS is associated with increased levels of abdominal pain. We also show that increased fecal proteolytic activity is associated with increased abdominal pain in patients with IBS.

Functional gastrointestinal disorders (FGIDs) were highly prevalent and involve gastrointestinal discomfort characterized by non-organic abnormalities in the morphology and physiology of the gastrointestinal tract. According to the Rome IV criteria, irritable bowel syndrome and functional dyspepsia are the most common FGIDs. Complementary and alternative medicines are employed by increasing numbers of individuals around the world, and they include herbal and dietary supplements, acupuncture, and hypnosis. Of these, herbal and dietary supplements seem to have the greatest potential for relieving FGIDs, through multiple modes of action. However, despite the extensive application of natural extracts in alternative treatments for FGIDs, the safety and effectiveness of food and orally ingested food-derived extracts remain uncertain. Many randomized controlled trials have provided compelling evidence supporting their potential, as detailed in this review. The consumption of certain foods (eg, kiwifruit, mentha, ginger, etc) and food ingredients may contribute to the alleviation of symptoms associated with FGID,. However, it is crucial to emphasize that the short-term consumption of these components may not yield satisfactory efficacy. Physicians are advised to share both the benefits and potential risks of these alternative therapies with patients. Furthermore, larger randomized clinical trials with appropriate comparators are imperative.

Irritable bowel syndrome (IBS) is a multifactorial disorder of the gut-brain axis, characterized by visceral hypersensitivity (VH). Psychobiotics, through GABA synthesis, are good candidates to alleviate gastrointestinal discomfort. Here, we analyzed the GABA-producer Lactococcus lactis CNCM I-5388 as an active-enzyme postbiotic to relieve VH mediated by psychological stress. L. lactis CNCM I-5388 was inactivated by ethanol while maintaining its glutamate decarboxylase (GAD) activity. This EtOH-treated nonviable form was given daily orally for 1, 5, or 10 days to female Wistar rats in comparison with viable L. lactis CNCM I-5388 or vehicle. Visceral sensitivity was measured by electromyography before and after partial restraint stress (PRS). GABA was quantified in the stomach collected from rats and in the gastric compartment of TIM-1 human gut model in fed state. A daily treatment for 5 and 10 days by L. lactis CNCM I-5388 both in its viable and nonviable forms counteracted VH promoted by PRS. However, only viable L. lactis CNCM I-5388 tended to reduce VH after a single administration. After 5-day treatment, only under PRS conditions, the production of GABA within the stomach was enhanced in rats treated with viable or nonviable L. lactis CNCM I-5388. This increase was confirmed by using the TIM-1 human gut model. We found that a postbiotic with an active-GAD enzyme of L. lactis CNCM I-5388, similarly to its viable psychobiotic form, exerts anti-VH properties in an IBS-like rat model. These effects are associated with GABA production in the stomach where the low pH promotes GAD activity.

Systemic amyloidosis refers to a group of protein misfolding disorders resulting in organ deposition with amyloid, leading to organ dysfunction, ultimately resulting in organ failure and death if not successfully treated. Treatment is type-specific and aimed at the underlying source of the misfolded protein. In the past decades, treatments have become increasingly available across the various amyloidosis types with improved response rates and longer survival. Supportive care measures are an integral part of care for patients with systemic amyloidosis to improve symptom burden and quality of life, reduce healthcare costs, and potentially prolong survival while type-directed therapy takes effect. In these guidelines, we provide supportive care recommendations across eight areas of interest in systemic amyloidosis: cardiology, nephrology, peripheral neuropathy, central nervous system involvement, autonomic neuropathy, gastroenterology, coagulopathy and bleeding, nutrition and hematology. These guidelines were developed on behalf of the International Society of Amyloidosis (ISA) by experts in the above fields and provide the best available evidence and expertise for supportive care in these rare disorders.