This study evaluates the efficacy of the postbiotic Probio-Eco in alleviating constipation in humans and mice. A randomized, double-blind, placebo-controlled crossover trial involving 110 adults with chronic constipation (Rome IV criteria) demonstrates that a 3-week Probio-Eco intervention significantly improves constipation symptoms, stool straining, and worry scores. Gut microbiota and metabolomic analyses reveal modulations in specific gut microbiota, succinate, tryptophan derivatives, deoxycholate, propionate, butyrate, and cortisol, correlating with symptom relief. A loperamide-induced mouse model confirms that Probio-Eco and its bioactive components (succinate, 3-indoleacrylic acid, and 5-hydroxytryptophan) alleviate constipation by stimulating mucin-2 secretion, regulating intestinal transport hormones, and promoting anti-inflammatory responses. Multi-omics integration identifies key pathways, including succinate-short-chain fatty acid, tryptophan-5-hydroxytryptophan-serotonin, and tryptophan-3-indoleacrylic acid, driving intestinal homeostasis and motility. These findings highlight the comprehensive efficacy of Probio-Eco and provide robust evidence for its clinical application in constipation management. This study was registered at Chinese Clinical Trial Registry (ChiCTR2100054376).

Small intestinal bacterial overgrowth (SIBO) is a functional digestive disorder whose incidence has been acknowledged by several medical associations, such as the American Gastroenterological Association. It is estimated that between 14% and 40% of patients diagnosed with irritable bowel syndrome also have SIBO, highlighting the importance of accurate diagnosis to enable effective treatment plans. Nutrition and diet therapy play a pivotal role in SIBO management, not only in alleviating symptoms but also in preventing relapses. The objective of this review is to gather updated information on dietary management for SIBO to define the role of the dietitian and determine the most suitable nutritional therapy based on scientific evidence. The review will encompass various strategies, ranging from specific diets to dietary supplements, as well as the potential contribution of dietary treatment to improving SIBO.

Irritable bowel syndrome (IBS) is frequently observed in clinical practice and affects people from different parts of the world. The pathogenesis and aetiology are not well-defined or fully understood; however, altered bowel movements, psychological factors, and visceral hypersensitivity may contribute to symptoms via a pathway mediated by serotonin and other enteric neurotransmitters. Altered bowel movements, including diarrhoea and constipation, abdominal pain relieved by passing flatus, and bloating are the main salient features of this condition. This systematic review and meta-analysis aimed to determine the effectiveness and efficacy of a low-fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (low-FODMAP) diet in these patients. Systematic searches were conducted on PubMed, Medline, Google Scholar, and Cochrane Library. Randomised controlled trials (RCTs), systematic trials and cohort studies that included keywords about IBS and a low-FODMAP diet were included. Exclusion criteria included studies that were not in the English language, not relevant to IBS, diet-related to inflammatory bowel disease, or not pertinent to the subject. A total of 41 studies were included in this systematic review and meta-analysis. There was significant heterogeneity among the RCTs; hence, a random-effects model was used. The systematic review included a total of 8460 patients across 36 studies, with follow-up durations ranging from 11 to 16 months. Specifically, the meta-analysis included 15 RCTs with 1118 participants and follow-up durations from two days to nine weeks and six cohort studies including 292 patients with follow-up durations from two weeks to two years. The risk ratio (RR) was 1.21 (95% confidence interval= 0.98-1.51), and the I2 value ​​​​​was 63% for global symptom improvement with a low-FODMAP diet using a random-effects model. There was a low risk of bias in the RCTs. Five studies were included evaluating the effect of a low-FODMAP diet on quality of life, and these studies did not show any statistically significant benefit of a low-FODMAP diet on quality of life, although a mean difference of 4.59 (95% CI 1.50-7.67) was observed. The risk of bias was moderate to severe in the observational studies included in this review. Food intolerance is increasingly recognised as a contributory factor in IBS, and its role in the pathogenesis and precipitation of symptoms is being explored. Specific mechanisms include the fermentation of FODMAPs by the gut microbiota, leading to gas production and subsequent symptoms.

Malva sylvestris L. is rich in mucilage and is traditionally used for the management of numerous ailments including gastrointestinal disorders. Functional constipation (FC) is a gastrointestinal condition characterized by defecation anomalies such as infrequent stools, difficulty in stool passage, or both in the absence of pathological abnormalities. FC can be reduced through lifestyle factors and dietary intervention. This consumer-based survey aimed to assess the efficacy of a M. sylvestris extract-based food supplement on the improvement of FC.

Healthy participants (n = 56), enrolled in a consumer-based survey, took a food supplement containing a chemically characterized M. sylvestris extract at a dose of 20 mL/day (containing 750 mg of M. sylvestris extract rich in food fiber and polyphenols) for 20 days on the advice of their pharmacist. The study evaluated bowel movement frequency (intestinal diary), stool consistency (Bristol Stool Form Scale, BSFS), and abdominal pain (Visual Analogue Scale, VAS), at baseline (T0), after 10 days (T1), and after 20 days (T2).

A significant increase in bowel movement frequency and stool consistency (p < 0.001) with a significant decrease in abdominal pain (p < 0.001) was observed. Additionally, this food supplement was well-tolerated as no adverse effects were reported by the enrolled subjects.

M. sylvestris-based food supplement showed promising effectiveness and satisfaction in improving FC in healthy subjects, however, randomized clinical studies are needed to confirm these preliminary results.

The worldwide incidence of constipation is exhibiting an increasing trend. The objective of this study was to assess the relationship between dietary components and the occurrence of constipation.

Sociodemographic characteristics data of participants experiencing constipation and those without were sourced from the National Health and Nutrition Examination Survey (NHANES; 2000-2010; n = 1903; ≥20 years). Sociodemographic characteristics of participants experiencing constipation and those without were sourced from the National Health and Nutrition Examination Survey (NHANES). Data from two 24-hour dietary recalls (n = 1696; participants aged 20 years and older) were utilized to compare the dietary intake of various food components between constipated and non-constipated individuals, as well as to investigate the relationship between food component consumption and constipation. Odds ratios (OR) were calculated using an adjusted model. The distribution of the data was illustrated through a histogram. Based on this distribution, vegetable intake was categorized into five groups (0-0.733, 0.733-1.47, 1.47-2.2, 2.2-2.93, 2.93-8) for the purpose of subgroup analysis.

The median age of individuals experiencing constipation is 41.5 years, with women accounting for 65.3% and men accounting for 34.7%. The consumption of fruits (constipated people = 0.79 cups/d; non-constipated people = 0.93 cups/d), vegetables (1.21 cups/d; 1.59 cups/d), dairy (1.68 cups/d; 1.55 cups/d), and oils (15.31 g/d; 19.61 g/d) is below the recommended dietary intake for both groups. After multivariable adjustment, vegetable consumption (OR: 0.74, 95% CI: 0.59-0.92, p = 0.008) and female (OR: 2.12, 95% CI: 1.38-3.24, p < 0.001) were identified as significant predictors of constipation. The subgroup analysis concerning vegetable consumption indicated a statistically significant result within Group (2.93,8 ] [OR: 0.2, 95% CI: 0.069-0.57].

The findings of the research suggest that it is advisable for individuals to consume a minimum of 2.93 cups of vegetables daily. Furthermore, females exhibit a significantly elevated risk of experiencing constipation. However, no association has been identified between constipation and either age or educational level.

Introduction: Irritable bowel syndrome (IBS) is a common condition that alters the quality of life of patients. A variety of dietary interventions have been introduced to address this debilitating condition. The low-FODMAP diet (LFD), gluten-free diet (GFD), and Mediterranean diet are examples showing efficacy. The aim of this network meta-analysis was to compare these interventions to find the best approach. Methods: We performed a systematic review of the available literature through 14 March 2024 in the following databases: Embase, PubMed, MEDLINE OVID, Web of Science, CINAHL Plus, and Cochrane Central. We only included randomized controlled trials (RCTs). We used a random effects model and conducted a direct meta-analysis based on the DerSimonian-Laird approach and a network meta-analysis based on the frequentist approach. Mean differences (MDs) with 95% confidence interval (CI) were calculated. The primary outcomes included IBS quality of life (IBS QOL) and IBS symptom severity scale (IBS-SSS). Results: We finalized 23 studies including 1689 IBS patients. In the direct meta-analysis, there was no statistically significant difference in any IBS score between GFD and either LFD or standard diet. Meanwhile, the LFD was statistically superior to the standard diet in the IBS-SSS (MD: -46.29, CI: -63.72--28.86, p < 0.01) and IBS QOL (MD: 4.06, CI: 0.72-7.41, p = 0.02). On ranking, the Mediterranean diet showed the greatest improvement in IBS-SSS, IBS-QOL, distension, dissatisfaction, and general life interference, followed by the LFD alone or in combination with the GFD. Conclusions: We demonstrated the efficacy of dietary interventions such as the LFD and Mediterranean diet in improving IBS. There is a need for large RCTs with head-to-head comparisons, particularly for the Mediterranean diet.

Bowel dysfunction can significantly impair quality of life. Adequate fibre intake is associated with good bowel health but intakes have been reported to be low in Ireland.

This study aimed to gather data on fibre intake and bowel habits in a cohort of adults at a university campus in Dublin, Ireland.

An online questionnaire was developed by adapting validated tools to assess habitual fibre intake and bowel function. The questionnaire was circulated through mailing lists and advertised via QR codes on campus in February/March 2023. Data was analysed using SPSS, p < 0.05 was considered statistically significant.

In total, 275 valid responses were received. Low fibre intakes (< 19 g/day) were found in 50.5% of participants. A significantly higher proportion of males had low fibre intake compared to females (62.2% vs 44.8%, p = 0.039). Nearly a third (30.2%) of respondents experienced mild symptoms of bowel dysfunction, and 13.1% experienced moderate to severe symptoms. An inverse relationship was observed between fibre intake (g/day) and bowel dysfunction (p = 0.033).

In this cohort, low fibre intakes and some degree of bowel dysfunction were prevalent. Public health campaigns to increase fibre intake could prove to be a cost-effective way to improve bowel function and health amongst adults in Ireland.

Chickpea is considered a rich source of nutrients, especially protein and dietary fibre. Besides, chickpea has potential benefits for the maintenance of gut health by improving intestinal integrity and serving as a source of energy for the gut microbiota. Moreover, chickpea consumption has been found to possess anti-cancer, anti-inflammatory, and antioxidant activity. On undergoing certain treatments like soaking, dehulling, roasting, and germination, the anti-nutritional profile of chickpeas can be reduced. Observing these benefits, this review explores the impact of chickpea and its components on maintaining gut health, emphasizing various benefits. Besides, the paper comprehensively covers the nutritional composition of chickpeas and factors influencing the bioavailability of its components concerning gut health. Additionally, it outlines the mechanisms through which chickpeas influence gastrointestinal health, providing valuable insights into complex processes and potential therapeutic applications. Furthermore, the review identifies contributions that can guide future research, encouraging further exploration of chickpeas' role in gut health and the development of interventions. As a result of the presented review, chickpeas can be used as an affordable source of food, which is nutritionally stable and prevents gastrointestinal diseases.

Diet plays an important role in management of gastrointestinal (GI) symptoms in patients with irritable bowel syndrome (IBS). Restrictive diets have gained popularity as treatment for IBS, but no studies have examined the patients' experiences of implementing such diets. Thus, the present study aimed to explore the experience of patients with IBS undergoing a structured dietary intervention.

Using inductive content analysis, semi-structured interviews were conducted in 19 patients with IBS, who were recruited from a randomised controlled trial evaluating two different restrictive diets for 4 weeks: a diet low in total carbohydrates; and a diet low in fermentable oligo-, di- and monosaccharides and polyols (i.e., FODMAP) combined with traditional IBS dietary advice.

Three main themes developed from the qualitative analysis and together they describe the dietary intervention as supportive, as well as the dietary changes as challenging and contributing to reflection. Patients found the dietary support effective in both initiating and adhering to their dietary changes. Despite the support, the implementation of the diet was perceived as challenging when it interfered with other important aspects of their lives. However, going through the dietary change process, the patients began to reflect on their eating behaviours, which enabled individual dietary adjustments. The adjustments that patients maintained were not only a result of alleviation of GI symptoms, but also based on personal preferences.

Patients with IBS undergoing restrictive diets appear to benefit from structured support. However, considering the individual patient's life situation and personal preferences, individualised dietary options should be encouraged to achieve long-term dietary changes.

Phytotherapeutics are gaining influence in the treatment of gastroenterological diseases. Their popularity and growing evidence of efficacy contribute to their integration into medical guidelines. A systematic screening identified recommended phytotherapeutic approaches. Based on current scientific data, some recommendations for the use of phytotherapeutic agents are given. For irritable bowel syndrome the use of peppermint oil is "strongly recommended", especially for pain and flatulence. Other phytotherapeutics such as STW-5, Tibetan Padma Lax or warm caraway oil pads have proven effective in alleviating symptoms. It is "recommended" to integrate them into the treatment concept. For chronic constipation, 30g of fiber per day is recommended. Best data exists for plantago psyllium with moderate evidence and chicory inulin. In case of ulcerative colitis, plantago psyllium as well as the combination of myrrh, chamomile flower extract, and coffee charcoal can be used as a complementary treatment in maintaining remission. There is also an "open recommendation" for curcumin for both, remission induction and maintenance. Some phytotherapeutic treatments (e.g., Artemisia absintium, Boswellia serata) show evidence of effectiveness for the treatment of Crohn's disease, but data are not yet sufficient for recommendations. Cannabis-based medicines can be considered for abdominal pain and clinically relevant appetite loss if standard therapy is ineffective or contraindicated, but they should not be used for acute inflammation in active Crohn's disease. Further recommendations for other gastroenterological diseases are discussed. The safety and tolerability of the phytotherapeutics were rated as predominantly "very good" to "acceptable". Some clear recommendations for the use of phytotherapeutics to treat gastroenterological diseases show their great potential. Due to their wide range of effects, phytotherapeutics can be used very well as a complement to conventional medicines in case of complex regulatory disorders. However, further methodologically well-conducted impact studies would be helpful in order to be able to make further recommendations.

Irritable bowel syndrome (IBS) is a pediatric pain-dominant functional gastrointestinal disorder that has a negative impact on all children's dimensions of quality of life. A dietary approach that focuses on limiting food elements with high fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) can be used to decrease symptoms of IBS. This study aims to evaluate the effect of low FODMAP dietary intervention on health-related quality of life among a sample of Egyptian children.

Eighty-four children aged 5-15 years old were randomly assigned to two groups, 42 patients in the low FODMAP diet group and 42 patients in the standard diet group. They received the diet for six weeks and were followed up weekly using a visual analog scale (VAS) for pain severity assessment, the Pediatric Quality of Life (PedsQL) Inventory Gastrointestinal (GI) Symptoms Module Scale, and the PedsQL Inventory Generic Core Scale to assess the physical and psychosocial functioning of the patients.

The VAS score decreased more in the low FODMAP group, which caused a significant difference between the two groups (p<0.001). The PedsQL Inventory GI Symptoms Module score increased more among the low FODMAP group, and this caused a significant difference between the two groups (p<0.001). PedsQL Inventory Generic Core score increased more among the low FODMAPs group, and this caused a significant difference between the two groups (p<0.001).

Low FODMAP dietary intervention in pediatrics for six weeks decreased abdominal pain severity, improved gastrointestinal symptoms, and improved the health-related quality of life of the affected children.

Functional gastrointestinal disorders (FGIDs) are a group of chronic or recurrent gastrointestinal functional diseases, including functional dyspepsia, irritable bowel syndrome, and functional constipation. A lack of safe and reliable treatments for abdominal pain-related FGIDs has prompted interest in new therapies. Evidence has shown that supplementation with dietary fiber may help treat FGIDs. Dietary fibers (DFs) have been demonstrated to have regulatory effects on the gut microbiota, microbiota metabolites, and gastrointestinal movement and have important implications for preventing and treating FGIDs. However, the adverse effects of some DFs, such as fermentable oligosaccharides, on FGIDs are unclear. This review provides an overview of the DFs physiological properties and functional characteristics that influence their use in management of FGIDs, with emphasis on structural modification technology to improve their therapeutic activities. The review highlights that the use of appropriate or novel fibers is a potential therapeutic approach for FGIDs.

Constipation suffered by children is a global public health problem. Functional constipation (FC) brings about deteriorating effects in the children's lives who suffer from it. The risk factors for the development of constipation include the consumption of a diet low in fiber and high in calories (such as the consumption of fast food), a sedentary lifestyle with a lack of exercise, a family history of constipation, and emotional and psychological stress endured by children in their families. It is one of the most common causes of stomachaches in children. FC may lead to fecal incontinence (FI), anal fissures, recurrent urinary tract infections (RUTI), and enuresis in children. Severe constipation may result in stool becoming rock-hard and inflexible in the rectum, which is clinically identified as fecal impaction. It is imperative to perform clinical evaluation and treatment, including pharmacological (the use of stimulant and osmotic laxatives) and non-pharmacological (education, changes in diet, intervention to promote positive behavior and address any emotional issues, toilet training, and physiotherapy for the pelvic floor) interventions. In the case of refractory patients, neuromodulation, the irrigation of the anal canal, and surgical management may be needed. It is essential to lead a healthy, stress-free lifestyle with plenty of exercise and a balanced diet rich in fiber (such as fruits and vegetables) so children can have regular bowel habits and thrive.

According to unofficial data, every fifth person in Serbia suffers from some form of irritable bowel syndrome (IBS). Compounds classified as FODMAPs (Fermentable Oligo-, Di-, and Monosaccharides and Polyols) are newly found potential triggers of IBS and a number of associated gastrointestinal disorders. Cereals, predominantly in their wholegrain form, represent the key contributors to the high contents of FODMAPs in wholegrain (high-fiber) bakery products. The current work was structured in a way to systematically evaluate the consumer's knowledge and preferences toward wholegrain and low-FODMAP bakery products. The questionnaire was filled out by 725 respondents, aged from 18 to 86 years. They were informed about the aim of the research and management of anonymous data. The present study is the first detailed survey in this region of Europe, aiming to improve the familiarity with and attitude toward FODMAPs and a low-FODMAP diet by analyzing the different dietary habits regarding wholegrain-cereal-based products among consumers of various ages, genders, places of residence, and education. The results suggest that the respondents are, to some degree, aware of the health benefits of consuming foods with high fiber content while indicating a low level of knowledge about FODMAP compounds and connected topics. Education about contemporary scientific findings and the potentially harmful effects of consuming FODMAP compounds for a population with gastrointestinal disorders and diseases will be imperative in the future.

Functional constipation (FC) is a common intestinal disease worldwide. Despite the presence of criteria such as Roman IV, there is no standardized diagnosis and treatment algorithm in Hong Kong that combines both Western and Chinese medicine approaches. This study integrates current effective and safe diagnosis and treatment methods for FC and provides a clear and scientific pathway for clinical professionals and patients.

A systematic search of the PubMed, Cochrane Library, and China National Knowledge Infrastructure databases was performed from their inception to June 30th, 2022, collecting the current evidence about the efficacious integrative management for FC. We organized a meeting of professionals in fields relevant to treatment and management of FC to develop a consensus agreement on clinical pathway process.

We developed a clinical pathway for the treatment of FC based on the most recent published guidelines and consultation with experts. This pathway includes a hierarchy of recommendations for every step of the clinical process, including clinical intake, diagnostic examination, recommended labs, diagnostic flowchart, and guidance for selection of therapeutic drugs.

This pathway establishes clinical standards for the diagnosis and treatment of FC using Chinese medicine and Western medicine; it will help to provide high-quality medical services in Hong Kong for patients with FC. Please cite this article as: Wei DJ, Li HJ, Lyu ZP, Lyu AP, Bian ZX, Zhong LL. A clinical pathway for integrative medicine in the treatment of functional constipation in Hong Kong, China. J Integr Med. 2023; 21(6): 550-560.

There remains uncertainty as to which risk factors are important for the development of defaecatory problems as a result of heterogeneity of published evidence. Understanding the impact of risk factors may be important in selecting targets for disease prevention or reversal. The aim of this study was to identify and evaluate risk factors for faecal incontinence and chronic constipation.

Risk factors for chronic constipation and faecal incontinence were long-listed from scientific literature, then anonymously evaluated (by 50 predominantly colorectal surgical experts from the UK Pelvic Floor Society) using a Delphi technique. Each risk factor was rated as independent, a co-factor, or not a risk factor. Independent risk factors were rated between 1 (not important) and 10 (critically important) with mean (± standard deviation) calculated.

Thirty-eight risk factors for chronic constipation were evaluated. Eighteen were classed as independent and 16 as co-factors. Opioid analgesia (7.87 ± 2.05), eating disorders (7.80 ± 1.72), and history of abuse (7.70 ± 1.89) were scored as most important independent risk factors. Female sex (6.60 ± 2.02) was considered an independent risk factor but increasing age was rated a co-factor. Thirty-three risk factors for faecal incontinence were evaluated. Twenty were classed as independent and eight as co-factors. Third- or fourth-degree tear (8.88 ± 1.57), instrumental delivery (8.47 ± 1.58), and grand multiparity (8.00 ± 1.63) were rated most important. Increasing age (7.41 ± 2.14) and female sex (7.58 ± 2.05) were both considered independent risk factors.

Several risk factors for chronic constipation and faecal incontinence were selected by Delphi approach. These factors will feed forward into Bayesian models of disease prediction that combine data and expert knowledge.

Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits. It can be subclassified in different subtypes according to the main clinical manifestation: constipation, diarrhea, mixed, and unclassified. Over the past decade, the role of gut microbiota in IBS has garnered significant attention in the scientific community. Emerging research spotlights the intricate involvement of microbiota dysbiosis in IBS pathogenesis. Studies have demonstrated reduced microbial diversity and stability and specific microbial alterations for each disease subgroup. Microbiota-targeted treatments, such as antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and even diet, offer exciting prospects for managing IBS. However, definitive conclusions are hindered by the heterogeneity of these studies. Further research should focus on elucidating the mechanisms, developing microbiome-based diagnostics, and enabling personalized therapies tailored to an individual's microbiome profile. This review takes a deep dive into the microscopic world inhabiting our guts, and its implications for IBS. Our aim is to elucidate the complex interplay between gut microbiota and each IBS subtype, exploring novel microbiota-targeted treatments and providing a comprehensive overview of the current state of knowledge.

During the last decade, scientific interest in and consumer attention to sourdough fermentation in bread making has increased. On the one hand, this technology may favorably impact product quality, including flavor and shelf-life of bakery products; on the other hand, some cereal components, especially in wheat and rye, which are known to cause adverse reactions in a small subset of the population, can be partially modified or degraded. The latter potentially reduces their harmful effects, but depends strongly on the composition of sourdough microbiota, processing conditions and the resulting acidification. Tolerability, nutritional composition, potential health effects and consumer acceptance of sourdough bread are often suggested to be superior compared to yeast-leavened bread. However, the advantages of sourdough fermentation claimed in many publications rely mostly on data from chemical and in vitro analyzes, which raises questions about the actual impact on human nutrition. This review focuses on grain components, which may cause adverse effects in humans and the effect of sourdough microbiota on their structure, quantity and biological properties. Furthermore, presumed benefits of secondary metabolites and reduction of contaminants are discussed. The benefits claimed deriving from in vitro and in vivo experiments will be evaluated across a broader spectrum in terms of clinically relevant effects on human health. Accordingly, this critical review aims to contribute to a better understanding of the extent to which sourdough bread may result in measurable health benefits in humans.

Fibre-based dietary interventions are at the forefront of gut microbiome modulation research, with a wealth of 16S rRNA information to demonstrate the prebiotic effects of isolated fibres. However, there is a distinct lack of data relating to the effect of a combination of soluble and insoluble fibres in a convenient-to-consume fruit juice food matrix on gut microbiota structure, diversity, and function. Here, we aimed to determine the impact of the MOJU Prebiotic Shot, an apple, lemon, ginger, and raspberry fruit juice drink blend containing chicory inulin, baobab, golden kiwi, and green banana powders, on gut microbiota structure and function. Healthy adults (n = 20) were included in a randomised, double-blind, placebo-controlled, cross-over study, receiving 60 mL MOJU Prebiotic Shot or placebo (without the fibre mix) for 3 weeks with a 3-week washout period between interventions. Shotgun metagenomics revealed significant between-group differences in alpha and beta diversity. In addition, the relative abundance of the phyla Actinobacteria and Desulfobacteria was significantly increased as a result of the prebiotic intervention. Nine species were observed to be differentially abundant (uncorrected p-value of <0.05) as a result of the prebiotic treatment. Of these, Bifidobacterium adolescentis and CAG-81 sp900066785 (Lachnospiraceae) were present at increased abundance relative to baseline. Additionally, KEGG analysis showed an increased abundance in pathways associated with arginine biosynthesis and phenylacetate degradation during the prebiotic treatment. Our results show the effects of the daily consumption of 60 mL MOJU Prebiotic Shot for 3 weeks and provide insight into the functional potential of B. adolescentis.

Irritable bowel syndrome (IBS) is associated with various gastrointestinal and nongastrointestinal symptoms and reduced quality of life. A diet low in fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) is one therapeutic option for IBS. Although the efficacy of the low FODMAP diet has been reported in several systematic reviews, the efficacy-effectiveness gap of the low FODMAP diet has not yet been assessed.

This systematic review aims to compare the efficacy of the low FODMAP diet from efficacy randomized controlled trials (RCTs) with the effectiveness of studies conducted in "real-world" settings.

RCTs, prospective and retrospective cohort studies, and retrospective audits assessing the low FODMAP diet in adults with IBS will be searched in 4 databases: Embase, MEDLINE, CENTRAL, and CINAHL. Two independent reviewers will perform study selection, data extraction, and risk of bias assessment and assess selected quality aspects from the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) protocol. Outcomes assessed are stool frequency, stool consistency, abdominal pain, overall symptom scores, adequate symptom relief, IBS-specific quality of life, and diet adherence. Data will be summarized with forest plots without summary statistics, tables, and narrative descriptions.

The search, title and abstract screening, and full-text screening were completed in March 2021, and an updated search was done in May 2022. As of May 2023, data analysis is almost finished, and manuscript writing is in progress. Submission of the manuscript is expected by July 2023.

The findings of this systematic review will compare the efficacy of the low FODMAP diet for IBS found in RCTs to the diet's real-world effectiveness.

PROSPERO CRD42021278952; https://tinyurl.com/32jk43ev.

DERR1-10.2196/41399.

Apples are known to exhibit various beneficial effects on human health. In the present study, we investigated the effect of continuous intake of apple juice (AJ) on constipation status. A single dose of loperamide in rats as the constipation model markedly decreased the weight and number of fecal pellets compared to saline-administered rats as a control. After the administration of AJ twice a day for seven days, recovery of defecation close to that of the control was observed in loperamide-treated rats. In addition, the total bile acid content in the feces increased from day 4 after the administration of AJ. Among hepatic and intestinal transporters and enzymes that regulate bile acids, the mRNA expression of the apical sodium-dependent bile acid transporter (Asbt, slc10a2) was decreased by AJ in rats. Furthermore, the Asbt-mediated bile acid transport activity in the rat ileum decreased after AJ administration. Moreover, in human colonic cancer-derived Caco-2 cells, AJ exposure for 24 and 48 h decreased the expressions of ASBT mRNA and protein, and the uptake activity of taurocholic acid in both 7- and 21-d cultures. Several components of AJ, such as procyanidins, decreased the expression of ASBT in Caco-2 cells. In conclusion, ASBT downregulation is a possible mechanism responsible for the constipation-relieving effect of apples, and procyanidins may play a role in downregulating ASBT, which leads to the beneficial effects of apples against constipation. Although it is generally agreed that the common dietary compositions play a role in constipation relief, the novel specific mechanism of apples found in this study would facilitate understanding food functions.

A placebo-controlled, randomized, double-blind study was conducted to evaluate the effect of taking 25 billion colony-forming units of heat-killed Bifidobacterium longum CLA8013 over 2 weeks on bowel movements in constipation-prone healthy individuals. The primary endpoint was the change in defecation frequency between the baseline and 2 weeks after the intake of B. longum CLA8013. The secondary endpoints were the number of days of defecation, stool volume, stool consistency, straining during defecation, pain during defecation, feeling of incomplete evacuation after defecation, abdominal bloating, fecal water content, and the Japanese version of the Patient Assessment of Constipation Quality of Life. A total of 120 individuals were assigned to two groups, 104 (control group, n=51; treatment group, n=53) of whom were included in the analysis. After 2 weeks of consuming the heat-killed B. longum CLA8013, defecation frequency increased significantly in the treatment group compared with that in the control group. Furthermore, compared with the control group, the treatment group showed a significant increase in stool volume and significant improvement in stool consistency, straining during defecation, and pain during defecation. No adverse events attributable to the heat-killed B. longum CLA8013 were observed during the study period. This study revealed that heat-killed B. longum CLA8013 improved the bowel movements of constipation-prone healthy individuals and confirmed that there were no relevant safety issues.

About one-third of chronically constipated patients have an evacuation disorder, and dyssynergic defecation is a common cause of the evacuation disorder. In dyssynergic defecation, the coordination between abdominal and pelvic floor muscles during defecation is disrupted and patients cannot produce a normal bowel movement. The etiology of dyssynergic defecation is still unknown. Although a detailed history taking and a careful examination including digital rectal examination could be useful, other modalities such as anorectal manometry and balloon expulsion test are necessary for the diagnosis. Biofeedback therapy is one of the most effective and safe treatments. Here, we provide an overview of dyssynergic defecation as well as how to diagnose and manage this condition.

The irritable bowel syndrome (IBS) is a chronic disorder of gut-brain interaction. IBS is still associated with areas of uncertainties, especially regarding the optimal diagnostic work-up and the more appropriate management. Experts from 7 Italian Societies conducted a Delphi consensus with literature summary and voting process on 27 statements. Recommendations and quality of evidence were evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus was defined as >80% agreement and reached for all statements. In terms of diagnosis, the consensus supports a positive diagnostic strategy with a symptom-based approach, including the psychological comorbidities assessment and the exclusion of alarm symptoms, together with the digital rectal examination, full blood count, C-reactive protein, serology for coeliac disease, and fecal calprotectin assessment. Colonoscopy should be recommended in patients with alarm features. Regarding treatment, the consensus strongly supports a dietary approach for patients with IBS, the use of soluble fiber, secretagogues, tricyclic antidepressants, psychologically directed therapies and, only in specific IBS subtypes, rifaximin. A conditional recommendation was achieved for probiotics, polyethylene glycol, antispasmodics, selective serotonin reuptake inhibitors and, only in specific IBS subtypes, 5-HT3 antagonists, 5-HT4 agonists, bile acid sequestrants.

Oral nutrition supplements (ONS) are widely recommended for the management of unintentional weight loss in patient populations, long-term care residents, and community-dwelling older adults. Most marketed ONS are ultra-processed, with precision nutrition and aseptic composition, as well as convenience and availability, driving their selection. However, therapeutic effectiveness is mixed and the potential health risks of consuming ultra-processed ONS long-term in lieu of less-processed foods have received little attention. A diverse and balanced microbiota supporting immunity and wellness is maintained by a diet rich in plant-sourced foods. The implications of ultra-processed ONS displacing plant-sourced foods, and specifically the potential for undesirable impacts on the gut microbiota, require consideration. Most ONS are either devoid of fiber or are supplemented with isolated or purified fibers that may contribute to adverse gastrointestinal symptoms and appetite suppression. In contrast, the diversity of microbial-available, nondigestible carbohydrates, together with the array of phytochemicals found in plant-sourced foods, support microbial diversity and its resiliency. This review outlines the clinical dilemma of recommending commercial ultra-processed ONS vs nutritionally adequate (eg, high-energy/high-protein) foods and beverages that contribute to diet quality, maintenance of a diverse and stable gut microbiota composition, and support nutrition status and health. Ultra-processed ONS may fall short of expected health benefits, and overreliance may potentially contribute to the risk for patient and older adult populations because of the displacement of a variety of healthful foods.

Plant-based proteins are generally characterised by lower Indispensable Amino Acid (IAA) content, digestibility, and anabolic properties, compared to animal-based proteins. However, they are environmentally friendlier, and wider consumption is advocated. Older adults have higher dietary protein needs to prevent sarcopenia, a disease marked by an accelerated loss of muscle mass and function. Given the lower environmental footprint of plant-based proteins and the importance of optimising dietary protein quality among older adults, this paper aims to assess the net peripheral Amino Acid (AA) appearance after ingestion of three different plant protein and fibre (PPF) products, compared to whey protein with added fibre (WPF), in healthy older adults. In a randomised, single-blind, crossover design, nine healthy men and women aged ≥65 years consumed four test meals balanced in AA according to the FAO reference protein for humans, matched for leucine, to optimally stimulate muscle protein synthesis in older adults. A fasted blood sample was drawn at each visit before consuming the test meal, followed by postprandial arterialise blood sampling every 30 min for 3 h. The test meal was composed of a soup containing either WPF or PPF 1-3. The PPF blends comprised pea proteins with varying additional rice, pumpkin, soy, oat, and/or almond protein. PPF product ingestion resulted in a lower maximal increase of postprandial leucine concentration and the sum of branched-chain AA (BCAA) and IAA concentrations, compared to WPF, with no effect on their incremental area under the curve. Plasma methionine and cysteine, and to a lesser extent threonine, appearance were limited after consuming the PPF products, but not WPF. Despite equal leucine doses, the WPF induced greater postprandial insulin concentrations than the PPF products. In conclusion, the postprandial appearance of AA is highly dependent on the protein source in older adults, despite providing equivalent IAA levels and dietary fibre. Coupled with lower insulin concentrations, this could imply less anabolic potential. Further investigation is required to understand the applicability of plant-based proteins in healthy older adults.

These post hoc analyses provide clinically relevant data concerning time to response for individual irritable bowel syndrome with constipation (IBS-C) symptoms after linaclotide use.

Time-to-response data were pooled from 4 randomized controlled trials. Response time for abdominal symptoms (pain, discomfort, and bloating) and complete spontaneous bowel movements (CSBMs) were analyzed using the Kaplan-Meier method; patients were categorized as early responders (≤4 weeks), late responders (>4-12 weeks), or nonresponders.

Among 2,350 patients (1,172 placebo and 1,178 linaclotide 290 μg), >50% of patients with IBS-C who initiated linaclotide treatment experienced a decrease of ≥30% in abdominal pain, discomfort, or bloating within 3-4 weeks (median). The median time to achieving ≥3 CSBMs was 4 weeks. Although not all linaclotide-treated patients responded within 12 weeks, a late response occurred between 4 and 12 weeks in 1 in 6 patients for abdominal pain and in approximately 1 in 10 patients for CSBM frequency. Comparisons of early responders, late responders, and nonresponders for both response definitions indicated that women, Whites, and patients with less severe baseline abdominal symptoms were more likely to respond early.

Although treatment responses with linaclotide occurred in >50% of patients with IBS-C within 4 weeks of treatment initiation, benefits for individual abdominal symptoms and/or CSBM frequency can still occur between 4 and 12 weeks. A lack of improvement in one symptom does not negate the possibility of response for others, highlighting the importance of discussing all symptoms with patients and not assuming treatment futility at 4 weeks.

Functional constipation (FC) is prevalent worldwide and is an increasingly prominent problem among university students. However, there is a paucity of research on FC in university students. This study aimed to assess the prevalence of FC among Chinese university students by the Rome III criteria and investigate its associated factors. This cross-sectional study was conducted by online questionnaires among 929 university students at a Chinese university. Food consumption was assessed with the Semi-Quantitative Food Frequency Questionnaire (SQFFQ) and dietary patterns were analyzed using factor analysis. A binary logistic regression model was applied to clarify FC-associated factors. The prevalence of FC among university students was 5.1%. Interestingly, among university students, the prevalence of FC with “complex” dietary pattern was significantly higher than those with “vegetable, fruit, egg and milk-based” and “livestock and aquatic product-based” dietary pattern (9.9% vs. 3.1% vs. 2.8%, p < 0.001). The prevalence of FC was significantly higher among university students with moderate to severe sleep disorders than those with the other sleep status (χ2 = 18.100, p < 0.001). Furthermore, after adjusting the covariates, “complex” dietary pattern (OR = 4.023, p < 0.001), moderate to severe sleep disorders (OR = 3.003, p = 0.006), overeating (OR = 2.502, p = 0.032), long mealtime (>30 min) (OR = 6.001, p = 0.007), and poor defecation habits (OR = 3.069, p = 0.042) were positively associated with FC among university students. Based on the above-associated factors for FC, improving dietary patterns and sleep status and developing good bowel and dietary habits are essential to prevent and alleviate university students’ FC.

Colonic motility disorders may be influenced by the gut microbiota, which plays a role in modulating sensory and motor function. However, existing data are inconsistent, possibly due to complex disease pathophysiology, fluctuation in symptoms, and difficulty characterizing high-resolution taxonomic composition and function of the gut microbiome.

Increasingly, human studies have reported associations between gut microbiome features and colonic motility disorders, such as irritable bowel syndrome and constipation. Several microbial metabolites have been identified as regulators of colonic motility in animal models. Modulation of the gut microbiota via dietary intervention, probiotics, and fecal microbiota transplant is a promising avenue for treatment for these diseases. An integration of longitudinal multi-omics data will facilitate further understanding of the causal effects of dysbiosis on disease. Further understanding of the microbiome-driven mechanisms underlying colonic motility disorders may be leveraged to develop personalized, microbiota-based approaches for disease prevention and treatment.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder leading to chronic debilitating issues. A healthy diet plays an integral role in maintaining the gut microbiota equilibrium, thus promoting digestive health. The structure and function of gut microbiota are affected by genetics and environmental factors, such as altered dietary habits, gastroenteritis, stress, increased use of alcohol and drugs, and medication use. Whereas there are various management approaches cited in the literature to manage symptoms of IBS, the purpose of this article is to focus on dietary options that will restore the gut microbiome and help in managing IBS symptoms. Some of the diets that are discussed in this article include a low-FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) diet, gluten-free/wheat-free diet, high-fiber diet, dietary and herbal supplements (psyllium, peppermint oil), and probiotics/prebiotics/synbiotics. The clinical practice guidelines recommended by the American College of Gastroenterology outlines evidence-based dietary recommendations for patients with IBS to manage symptoms. Recent advancements in the dietary management of IBS highlighting the use of a patient-centered, personalized nutrition approach along with lifestyle changes, pharmacological therapies, and psychosocial and behavioral interventions are also reviewed and discussed.

Dietary interventions may alleviate symptoms related to functional gastrointestinal disorders, now termed disorders of gut-brain interaction. We reviewed which interventions have high-quality data to support their use in gastroesophageal reflux disease (GERD), functional dyspepsia (FD), irritable bowel syndrome, and chronic idiopathic constipation.

Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder in children and adults, which increased over the past twenty years. The Mediterranean diet is a well-known diet full of antioxidants and anti-inflammatory ingredients.

To evaluate the safety, tolerability, and effects of adherence to the Mediterranean diet on disease patterns in children and adolescents with IBS.

This prospective, cross-sectional case-controlled study included 100 consecutive IBS patients diagnosed according to Rome IV criteria, aged 12-18 years. Patients were subdivided into two groups (50 patients each); Group I received a Mediterranean diet, and Group II on their regular diet for six months. Besides IBS scores (IBS-SSS, IBS-QoL, and total score), different clinical and laboratory parameters were evaluated at the start and end of the study.

The Mediterranean diet was safe and well-tolerated in IBS patients. IBS children and adolescents with good adherence to the Mediterranean diet (KIDMED Score ≥ 8 points); group I showed significant improvement in IBS scores. IBS-SSS in the Mediterranean diet group was 237.2 ± 65 at the beginning of the study and decreased to 163.2 ± 33.8 at the end of the study (P < 0.001). It did not show a significant improvement in the group with a regular diet (248.3 ± 71.1 at the beginning of the study compared to 228.5 ± 54.3 at the study end with P < 0.05). The mean IBS-SSS in the Mediterranean diet group significantly improved compared with the group with a regular diet. Mean IBS-QoL in group I improved from 57.3 ± 12.9 at the start of the study to 72.4 ± 11.2 at the study end (P < 0.001) and significantly improved when compared to its level in group II at the study end (59.2 ± 12.7 with P < 0.001), while group II showed no significant improvement in IBS-QoL at the study end when compared to the beginning of the study (59.2 ± 11.7 with P >0.05). The mean total IBS score in group I became 28.8 ± 11.2 at the end of our study compared to 24.1 ± 10.4 at the start (P < 0.05) and significantly improved when compared to its level in group II at the end of the study (22.1 ± 12.5 with P < 0.05), while in group II, non-significant improvement in the total score at the end of our study compared to its mean level at the start of the study (22.8 ± 13.5 with P > 0.05).

The Mediterranean diet was safe and associated with significant improvement in IBS scores in children and adolescent patients with IBS.

Irritable bowel syndrome (IBS) is a prevalent and complex gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits. Observational studies have suggested a relationship between serum vitamin D levels and IBS symptoms. This systematic review and meta-analysis aimed to investigate the clinical effects of vitamin D supplementation on IBS symptom severity and quality of life (QoL) measures.

Medline, Embase, Scopus, Web of Science, and The Cochrane Library databases were systematically searched. Data abstraction and quality assessment were conducted by four authors independently, and discrepancies were resolved through consensus from the senior author. Continuous data were pooled with standardized mean difference (SMD) using the DerSimonian and Laird's random-effects model. Sensitivity analysis by risk of bias and potentially "predatory" publication were performed as well.

A total of 685 patients across eight studies were included in the meta-analysis. Vitamin D supplementation significantly improved IBS symptom severity scale scores, with a SMD of -0.77 (95% confidence interval [CI] -1.47 to -0.07, P = 0.04, I2  = 91%). Improvements in IBS-QoL scores were also observed, albeit not statistically significant (SMD 0.54; 95% CI -0.34 to 1.41, P = 0.15, I2  = 87%). However, small sample sizes, a relatively young study population, limited ethnicities, and varied vitamin D dosing strategies across the studies were notable limitations.

Vitamin D supplementation could be part of our clinical armamentarium when managing IBS patients due to the potential efficacy and good safety profile. Further randomized, controlled trials are required to confirm the therapeutic effects.

Whole grains are a pivotal food category for the human diet and represent an invaluable source of carbohydrates, proteins, fibers, phytocompunds, minerals, and vitamins. Many studies have shown that the consumption of whole grains is linked to a reduced risk of cancer, cardiovascular diseases, and type 2 diabetes and other chronic diseases. However, several of their positive health effects seem to disappear when grains are consumed in the refined form. Herein we review the available literature on whole grains with a focus on molecular composition and health benefits on many chronic diseases with the aim to offer an updated and pragmatic reference for physicians and nutrition professionals.

Chronic idiopathic constipation and irritable bowel syndrome with constipation are complex, overlapping conditions. Although multiple guidelines have informed healthcare providers on appropriate treatment options for patients with chronic idiopathic constipation and irritable bowel syndrome with constipation, little direction is offered on treatment selection. First-line treatment options usually include fiber and over-the-counter osmotic laxatives; however, these are insufficient for many individuals. When these options fail, prescription secretagogues (plecanatide, linaclotide, lubiprostone, and tenapanor [pending commercial availability]), or serotonergic agents (prucalopride and tegaserod) are generally preferred. Individuals experiencing concurrent abdominal pain and/or bloating may experience greater overall improvements from prescription therapies because these agents have been proven to reduce concurrent abdominal and bowel symptoms. Should initial prescription treatments fail, retrying past treatment options (if not adequately trialed initially), combining agents from alternative classes, or use of adjunctive therapies may be considered. Given the broad spectrum of available agents, therapy should be tailored by mutual decision-making between the patient and practitioner. Overall, patients need to be actively monitored and managed to maximize clinical outcomes.

Among other factors, food intolerance is cardinal in triggering irritable bowel syndrome (IBS) symptoms in a significant percentage of patients. As a result, specific dietary patterns are the first-line therapeutic approach. The low-FODMAP diet (LFD) is gaining ground as the most well-documented diet intervention that significantly reduces IBS symptoms. Though the LFD improves symptoms, the diet's impact on intestinal low-grade inflammation, one of the cardinal mechanisms contributing to symptom development, remains doubtful. On the other hand, the Mediterranean diet (MedDiet) is recommended for chronic low-grade inflammation-related diseases because of its anti-inflammatory properties, derived predominantly from olive oil and phenolic compounds. Thus far, the role of a modified LFD, enriched with the MedDiet's anti-inflammatory components, has not been evaluated in IBS patients. This review aims to examine the hypothesis of a potential combination of the immunomodulatory effects of the MedDiet with the LFD to improve IBS symptoms.

It is widely believed that diet and the gut microbiota are strongly related to the occurrence and progression of inflammatory bowel disease (IBD), but the effects of the interaction between dietary patterns and the gut microbiota on IBD have not been well elucidated. In this article, we aim to explore the complex relation between dietary patterns, gut microbiota, and IBD. We first comprehensively summarized the dietary patterns associated with IBD and found that dietary patterns can modulate the occurrence and progression of IBD through various signaling pathways, including mammalian target of rapamycin (mTOR), mitogen-activated protein kinases (MAPKs), signal transducer and activator of transcription 3 (STAT3), and NF-κB. Besides, the gut microbiota performs a vital role in the progression of IBD, which can affect the expression of IBD susceptibility genes, such as dual oxidase 2 (DUOX2) and APOA-1 , the intestinal barrier (in particular, the expression of tight junction proteins), immune function (especially the homeostasis between effector and regulatory T cells) and the physiological metabolism, in particular, SCFAs, bile acids (BAs), and tryptophan metabolism. Finally, we reviewed the current knowledge on the interaction between dietary patterns and the gut microbiota in IBD and found that dietary patterns modulate the onset and progression of IBD, which is partly attributed to the regulation of the gut microbiota (especially SCFAs-producing bacteria and Escherichia coli). Faecalibacteria as "microbiomarkers" of IBD could be used as a target for dietary interventions to alleviate IBD. A comprehensive understanding of the interplay between dietary intake, gut microbiota, and IBD will facilitate the development of personalized dietary strategies based on the regulation of the gut microbiota in IBD and expedite the era of precision nutritional interventions for IBD.

Functional constipation (FC) is a common bowel disorder that prevails worldwide. In China, although a heterogeneous prevalence of constipation is expected, it is currently not demonstrated. In this study, we aimed to evaluate the prevalence and related risk factors of FC in the Chinese population, according to the Rome criteria.

We searched the PubMed, the Embase, the Cochrane Library, the Web of Science, the China National Knowledge Infrastructure (CNKI), the Wanfang data knowledge service platform, the VIP information resource integration service platform, and the Chinese Biomedical Literature Service System (SinoMed) databases from the inception of database to July 2021. Population-based cross-section studies that enrolled adults with FC, diagnosed by the Rome criteria, were deemed eligible. We summarized the overall prevalence and detected the subgroup effect per the Rome I, Rome II, Rome III, and Rome IV criteria. We used the generalized linear mixed model (GLMM) with a random-effect intercept to pool the prevalence and performed pairwise meta-analyses for prevalence comparisons by risk factors.

We identified 3,213 records through our database search, and 39 studies from China, comprising 1,240,79 participants, met the eligibility criteria for our study. The pooled overall prevalence of FC using the Rome criteria was 8.5% in China. Heterogeneous prevalence was detected within the Rome criteria (Rome II: 10.6%, 95% CI: 7.2-15.4; Rome III: 6.5%, 95% CI: 3.4-12.0; Rome IV: 8.1%, 95% CI: 5.6-11.8). The prevalence increased between 1991 and 2020 (from 5.5% with 95% CI: 3.6-8.2 between 1991 and 2000 to 10.9% with 95% CI: 5.5-20.4 between 2011 and 2020). Higher prevalence was found in women [odds ratio (OR) = 1.53, 95% CI: 1.31-1.78] and the elderly (≥70 years vs. ≤ 29 years: OR = 3.38, 95% CI: 2.16-5.30) than in men and the younger population. A high-fiber diet was associated with lower prevalence (OR = 0.33, 95% CI: 0.15-0.75), whereas irregular bowel habit and inactivity were associated with higher prevalence (OR = 3.64, 95% CI: 2.64-5.03; OR = 1.97, 95% CI: 1.14-3.43). Unhealthy mental states, such as anxiety and depression, and poor sleep quality led to high prevalence (OR = 3.16, 95%C I: 1.96-5.11; OR = 2.74, 95% CI: 1.76-4.26; OR = 2.14, 95% CI: 1.69-2.72, respectively).

Various types of FC prevail in China based on the different Rome criteria, personal characteristics, and habits. The prevalence also increased over the past three decades. The FC should be included under the primary care setting with uniform diagnosis criteria in China.

http://www.crd.york.ac.uk/PROSPERO, CRD42021277172.