Risk factors associated with intestinal permeability in an adult population: A systematic review.

BACKGROUND: Increased intestinal permeability (IP) involves the loss of integrity between the cells of the small intestine. IP has been suggested to contribute to the pathogenesis and exacerbation of many chronic diseases. Many potential risk factors for IP are proposed in contemporary literature. The purpose of this review is to identify the most significant risk factors for IP. METHODS: A systematic search of literature published up until September 2018 in the PubMed, EMBASE, CINAHL, and Scopus databases was conducted. RESULTS: A total of 47 articles met the inclusion criteria. Elevated levels of proinflammatory markers, dyslipidaemia, hyperglycaemia, insulin resistance, anthropometric measurements resembling obesity, advanced disease severity, comorbidity and the consumption of a Western-style diet were identified as the strongest risk factors for altered intestinal integrity. The risk of IP increases when coupled with a multiple disease state or combined with other environmental risk factors. Furthermore, many of the identified risk factors such as anthropometric measurements and biomarkers were external from intestinal health and rather resembled a metabolic-like condition. CONCLUSIONS: This review identified a number of potential risk factors for IP, ranging from biomarkers to anthropometric measurements, demographics, dietary intake and chronic diseases. These risk factors warrant the attention of clinicians and other healthcare providers to aid the identification of potential patients at risk of altered IP. Further research needs to examine whether the identified risk factors are homogeneous with the diagnosis of IP or whether the disease state influences the association.

The effects of kefir consumption on human health: a systematic review of randomized controlled trials.

CONTEXT: Kefir, a traditional, fermented-milk beverage, has increasingly been promoted for various health benefits. The evidence from systematic reviews, however, is limited. OBJECTIVE: Evidence from randomized controlled trials testing oral consumption of fermented-milk kefir on any outcome of human health or disease. DATA SOURCES: A systematic search of 4 electronic databases (PubMed, Scopus, Allied and Complementary Medicine Database, and Cochrane Trials) from inception to July 31, 2021, was conducted. DATA EXTRACTION: Data extraction and risk-of-bias assessments were conducted by 2 reviewers independently. DATA ANALYSIS: A total of 18 publications reporting the results of 16 studies were included. Per the narrative analysis, fermented-milk kefir may have potential as a complementary therapy in reducing oral Streptococcus mutans, thereby reducing dental caries risk, and in Helicobacter pylori eradication therapy. Kefir may further aid treatment of adult dyslipidemia and hypertension, although evidence was very limited. Safety was only assessed in 5 of the 18 included publications, and 12 of the studies had an overall high risk for bias. CONCLUSION: Kefir is a dairy product with a unique microbiological profile that appears to be a safe for generally healthy populations to consume. However, efficacy and safety data from high-quality human trials are essential before any recommendations may be made for conditions of the oral and gastric microbiota and metabolic health. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42020211494.

Health-seeking behaviour, views and preferences of adults with suspected increased intestinal permeability: A cross-sectional survey of Australian adults.

BACKGROUND: The public health consequence of increased intestinal permeability (IP) is currently limited by the lack of patient-centred research. This study aims to describe the health-seeking behaviour of Australian adults with suspected IP. METHODS: A cross-sectional survey of 589 Australian adults who have been diagnosed with IP or have suspected (undiagnosed) IP. RESULTS: The majority (56.2%) of participants with suspected IP reported self-diagnosing their condition, with the majority (56.7%) of these participants preferring to be assessed using an accurate method by a general practitioner or naturopath. On average, Australian adults with suspected IP spent 11.1 (95% CI: 9.5, 12.8) years between first suspecting IP and receiving a formal diagnosis. Over the previous 12 months, participants spent an average of $699 on consultation fees, $2176 on dietary supplements for the treatment of IP, and an average of $287 on the assessment of IP. Furthermore, participants who find it difficult to live on their available household income spent significantly more (mean=$2963) on dietary supplements compared to participants who find it easy to live on their available household income ($1918) (p=0.015). CONCLUSION: The investigation of Australian adults with suspected IP found the majority of participants experienced a considerable length of time between first suspecting IP and receiving a diagnosis of IP. The out-of-pocket expenditure associated with the management of IP suggests a financial burden for people with suspected IP. The results of this study provide novel patient-centred considerations that can be used to inform a clinical practice guideline for the management of IP.

Design characteristics of comparative effectiveness trials for the relief of symptomatic dyspepsia: A systematic review.

BACKGROUND: Dyspepsia represents a symptom domain rather than a diagnostic condition and covers a wide range of complex, underlying pathophysiologies that are not well understood. The review explores comparative effectiveness interventions for the treatment of symptomatic dyspepsia along a pragmatic-explanatory continuum. The aim is to identify relevant design characteristics applicable to future upper gastrointestinal comparative effectiveness research employing integrative medicine. METHODS: Medline, CINAHL, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL) and WHO Clinical Trials were systematically searched until January 2019. Included articles were original research with two or more comparative intervention arms for the primary outcome; relief of symptomatic dyspepsia. Evaluation of the studies was conducted using the pragmatic-explanatory continuum indicator summary (PRECIS-2) tool. RESULTS: Thirty-six articles were included in the review. A total of 68 Patient Reported Outcome Measurements (PROMs), utilizing 50 different formats were deployed across the studies. The appraisal process revealed eligibility, flexibility in adherence, flexibility in delivery and organization domains further aligned towards an explanatory design. CONCLUSION: This review identified three design characteristics relevant for future comparative effectiveness research for the treatment of upper gastrointestinal disorders in a community setting. Extensive exclusion eligibility criteria limited the generalization of comparative effectiveness study results by removing sub-groups of the target populations more at risk of dyspeptic symptoms. The requirement for entry endoscopy was found to be common and not always pragmatically justifiable. Development of validated PROMs appropriate for a generic application to upper gastrointestinal disorders would be advantageous for future comparative effectiveness research within integrative medicine.

The Subjective Well-being and Health-Related Quality of Life of Australian Adults with Increased Intestinal Permeability and Associations with Treatment Interventions.

Objective: The integrity and function of the gastrointestinal system is important in disease prevention and management. This study aims to describe the management methods used by Australian adults with suspected increased intestinal permeability (IP) and the association with subjective wellbeing (SWB) and health-related quality of life (HRQoL). Design and Setting: Cross-sectional survey of Australian adults diagnosed with IP or have suspected (undiagnosed) IP. Outcome Measures: Questionnaire items investigating demographic characteristics, self-reported outcome of IP and treatment methods used to manage IP. Participants' HRQoL and SWB according to the 20-Item Short Form Health Survey (SF-20) and Personal Wellbeing Index-Adult (PWI-A) scale, respectively. Results: Participants (n = 589) frequently used dietary products (87.9%), dietary supplements (72.9%) and lifestyle therapies (54.6%) for managing IP. Participants had lower (i.e., worse) mean SWB scores for all domains compared to the Australian population (p < 0.001). The number of days IP reported to affect daily living was negatively correlated with SWB and HRQoL (p < 0.001). Participants that reported an improvement in their IP in the previous 12 months were more likely to be treated by a healthcare practitioner (OR = 2.04, p = 0.015), use dietary supplements (OR = 2.66, p = 0.003), participate in vigorous exercise (OR = 2.99, p < 0.001) and employ vagus nerve stimulation (OR = 3.10, p = 0.010). Conversely, they were less likely to consume gluten (OR = 0.35, p < 0.001) or use nonsteroidal anti-inflammatory drugs (OR = 0.35, p = 0.022). Self-reported improvement of IP (ß = 10.70, p < 0.001) and use of dietary products (ß = 12.12, p = 0.008) were predictors of a higher level of SWB. Conclusions: Altered IP may pose a greater health burden than previously thought, with poor SWB and HRQoL reported in Australian adults with self-reported IP. Our results highlight the potential clinical relevance and consequence of altered IP, providing the first indication of a possible relationship between altered IP and both SWB and HRQoL.

Treatment Interventions for the Management of Intestinal Permeability: A Cross-Sectional Survey of Complementary and Integrative Medicine Practitioners.

Objectives: This study aims to explore the treatment interventions complementary and integrative medicine (CIM) practitioners use in the management of an emerging health condition, increased intestinal permeability (IP), and the association these methods have on the observed time to resolve this condition. Design and setting: A cross-sectional survey of Australian naturopaths, nutritionists, and Western herbal medicine practitioners was undertaken (n = 227) through the Practitioner Research and Collaboration Initiative (PRACI) network. Outcome measures: Frequencies and percentages of the treatment methods, including chi-square analysis to examine the associations between treatment methods and observed time to resolve IP. Results: Thirty-six CIM practitioners responded to the survey (response rate 15.9%). CIM practitioners were found to use a multimodal approach in the management of IP with 92.6% of respondents using three or more categories of treatment interventions (nutritional, herbal, dietary, and lifestyle) with a mean total of 43.0 ± 24.89 single treatment interventions frequently prescribed. The main treatments prescribed in the management of IP were zinc (85.2%), probiotics: multistrain (77.8%), vitamin D (75.0%), glutamine (73.1%), Curcuma longa (73.1%), and Saccharomyces boulardii (70.4%). CIM practitioners also advocate patients with IP to reduce alcohol (96.3%), gluten (85.2%), and dairy (75.0%) consumption. Evaluation of antibiotics (75.0%) and nonsteroidal anti-inflammatory drugs (73.1%) prescriptions were frequently advised by CIM practitioners. A longer observed time to resolve IP was seen in CIM practitioners who did not reduce intense exercise in the management of IP (p = 0.02). Conclusions: This study represents the first survey of the treatments prescribed by CIM practitioners for IP and suggests that CIM practitioners use numerous integrative treatment methods for the management of IP. The treatment interventions frequently prescribed by CIM practitioners align with preclinical research, suggesting that CIM practitioners prescribe in accordance with the published literature. The findings of this study contribute to the implementation of clinical research in the management of IP, which considers multiple concurrent treatments.

Investigation into complementary and integrative medicine practitioners' clinical experience of intestinal permeability: A cross-sectional survey.

BACKGROUND: This study aims to explore the conditions complementary and integrative medicine (CIM) practitioners associate with increased intestinal permeability (IP) and the methods they employ to assess IP. METHODS: A cross-sectional survey of naturopaths, nutritionists and Western herbal medicine practitioners was undertaken (n = 227) through the Practitioner Research and Collaboration Initiative (PRACI) network. RESULTS: CIM practitioners (n = 36, response rate 15.9%) associate IP with gastrointestinal (100.0%), autoimmune (91.7%), skin (91.7%), neurological (80.6%), respiratory (55.6%) and liver-related conditions (44.4%). CIM practitioners frequently treat IP (72.7%); observing a minimum 3 months of treatment is required to resolve IP. Patient's signs and symptoms were the main reasons CIM practitioners suspected IP (94.1%). CONCLUSION: CIM practitioners observe a clinical link between IP and a wide range of conditions, including those not yet recognised within the literature. The clinical experience of CIM practitioners holds substantial value to the advancement of research and the clinical management of IP.