Elemental Diet as a Therapeutic Modality: A Comprehensive Review.

Elemental diets have been employed for the management of various diseases for over 50 years, with several mechanisms mediating their beneficial effects. Yet, they are underutilized due to poor palatability, access, cost, and lack of awareness regarding their clinical efficacy. Therefore, in this review, we aimed to systematically search and review the literature to summarize the formulation variability, mechanisms of action, clinical applications, and tolerability of the elemental diets in gastrointestinal diseases. While large prospective trials are lacking, elemental diets appear to exhibit objective and subjective clinical benefit in several diseases, including eosinophilic esophagitis, eosinophilic gastroenteritis, inflammatory bowel diseases, small intestinal bacterial overgrowth, intestinal methanogen overgrowth, chemoradiotherapy-associated mucositis, and celiac disease. Although some data support the long-term use of elemental diets as an add-on supplement for chronic pancreatitis and Crohn's disease, most of the literature on exclusive elemental diets focuses on inducing remission. Therefore, subsequent treatment strategies for maintaining remission need to be adopted in chronic/relapsing diseases. Several mechanistic pathways were identified to mediate the effects of elemental diets, including food additive and allergen-free content, high passive absorption rate, and anti-inflammatory properties. High rates of intolerance up to 40% are seen in the trials where exclusive elemental diets were administered orally due to poor organoleptic acceptability; however, when tolerated, adverse events were rare. Other limitations of elemental diets are cost, access, and lifestyle/social restrictions. Moreover, judicious use is advised in presence of a concomitant restrictive food intake disorders. Elemental diets offer a potentially highly efficacious dietary intervention with minor side effects. Palatability, cost, access, and social restrictions are common barriers of use. Prospective clinical trials are needed to elucidate the role of elemental formulas in the management of individual diseases.

Prevalence of small intestinal bacterial overgrowth in intestinal failure syndrome: A systematic review and meta-analysis.

BACKGROUND AND AIM: Patients with intestinal failure (IF) have abnormal intestinal anatomy, secretion, and dysmotility, which impairs intestinal homeostatic mechanisms and may lead to small intestinal bacterial overgrowth (SIBO). We conducted a systematic review and meta-analysis to determine the prevalence of SIBO in patients with IF and to identify risk factors for SIBO. METHODS: MEDLINE (PubMed) and Embase electronic databases were searched from inception to December 2023 for studies that reported the prevalence of SIBO in IF. The prevalence rates, odds ratio (OR), and 95% confidence intervals of SIBO in IF and the risk factors for SIBO in IF were calculated using random effects model. RESULTS: Final dataset included nine studies reporting on 407 patients with IF. The prevalence of SIBO in IF was 57.5% (95% CI 44.6-69.4), with substantial heterogeneity in this analysis (I2 = 80.9, P = 0.0001). SIBO prevalence was sixfold higher in patients with IF who received parenteral nutrition (PN) compared with IF patients not on PN (OR = 6.0, 95% CI 3.0-11.9, P = 0.0001). Overall, the prevalence of SIBO in patients with IF using PPI/acid-suppressing agents (72.0%, 95% CI 57.5-83.8) was numerically higher compared with IF patients not using these agents (47.6%, 95% CI 25.7-70.2). CONCLUSIONS: This systematic review and meta-analysis suggests that there is an increased risk of SIBO in patients with IF and that PN, and potentially, the use of PPI/acid-suppressing agents is risk factors for SIBO development in patients with IF. However, the quality of evidence is low and can be attributed to lack of case-control studies and clinical heterogeneity seen in the studies.

Development of Polyphosphate/Nanokaolin-Modified Alginate Sponge by Gas-Foaming and Plasma Glow Discharge Methods for Ultrarapid Hemostasis in Noncompressible Bleeding.

Effective bleeding management strategies in uncontrollable and noncompressible massive hemorrhage are becoming important in both clinical and combat situations. Here, a novel approach was developed to create a superporous and highly absorbable hemostatic sponge through a facile chemical gas-foaming method by cross-linking long-chain polyphosphate along with nanokaolin and Ca2+ in an alginate structure to synergistically activate the coagulation pathway. Natural kaolin obtained from the Marand mine in East Azarbaijan was converted into pseudohexagonal-shaped kaolin nanoparticles (30 to 150 nm) using ball milling followed by a newly developed glow discharge plasma treatment method. The obtained ultralight sponges (>90% porosity) exhibit ultrarapid water/blood absorption capacity (∼4000%) and excellent shape memory, which effectively concentrates coagulation factors. The results of in vitro tests demonstrated that the proposed sponges exhibited enhanced blood clotting ability (BCI < 10%) and superior cohesion with red blood cells (∼100) and platelets (∼80%) compared to commercially available hemostatic products. The in vivo host response results exhibited biosafety with no systemic and significant local inflammatory response by hematological, pathological, and biochemical parameter assessments. In a rat femoral artery complete excision model, the application of alginate/k/polyp nanocomposite sponges resulted in a complete hemostasis time of 60 s by significant reduction of hemostasis time (∼6.7-8.3 fold) and blood loss (∼2-2.8-fold) compared to commercially available hemostatic agents (P < 0.001). In conclusion, distinct physical characteristics accompanied by unique chemical composition multifunctional sponges activate hemostasis synergistically by triggering the XII, XI, X, IX, V, and II factors and the contact pathway and have the ability of rapid hemostasis in noncompressible severe bleeding.

Characterization of the Small Bowel Microbiome Reveals Different Profiles in Human Subjects Who Are Overweight or Have Obesity.

INTRODUCTION: Gut microbiome changes are linked to obesity, but findings are based on stool data. In this article, we analyzed the duodenal microbiome and serum biomarkers in subjects with normal weight, overweight, and obesity. METHODS: Duodenal aspirates and serum samples were obtained from subjects undergoing standard-of-care esophagogastroduodenoscopy without colon preparation. Aspirate DNAs were analyzed by 16S rRNA and shotgun sequencing. Predicted microbial metabolic functions and serum levels of metabolic and inflammatory biomarkers were also assessed. RESULTS: Subjects with normal weight (N = 105), overweight (N = 67), and obesity (N = 42) were identified. Overweight-specific duodenal microbial features include lower relative abundance (RA) of Bifidobacterium species and Escherichia coli strain K-12 and higher Lactobacillus intestinalis , L. johnsonii , and Prevotella loescheii RA. Obesity-specific features include higher Lactobacillus gasseri RA and lower L. reuteri (subspecies rodentium ), Alloprevotella rava , and Leptotrichia spp RA. Escalation features (progressive changes from normal weight through obesity) include decreasing Bacteroides pyogenes , Staphylococcus hominis , and unknown Faecalibacterium species RA, increasing RA of unknown Lactobacillus and Mycobacterium species, and decreasing microbial potential for biogenic amines metabolism. De-escalation features (direction of change altered in normal to overweight and overweight to obesity) include Lactobacillus acidophilus , L. hominis , L. iners , and Bifidobacterium dentium . An unknown Lactobacillus species is associated with type IIa dyslipidemia and overweight, whereas Alloprevotella rava is associated with type IIb and IV dyslipidemias. DISCUSSION: Direct analysis of the duodenal microbiome has identified key genera associated with overweight and obesity, including some previously identified in stool, e.g., Bifidobacterium and Lactobacillus . Specific species and strains exhibit differing associations with overweight and obesity, including escalation and de-escalation features that may represent targets for future study and therapeutics.

Antifungal effects of echinocandins diminish when exposed to intestinal lumen contents: a finding with potentially significant clinical implications.

Echinocandins, a prominent class of antifungals, are known for their broad-spectrum activity and favorable safety profiles. However, their bioavailability and efficacy via oral route are suboptimal. In this study, caspofungin and micafungin, the two most commonly used echinocandins, were evaluated in various in vitro environments simulating intestinal lumen. The results revealed that while both antifungals are effective in standard medium, their efficacy significantly diminishes in the presence of human small bowel aspirates and bovine bile. The study suggests that bowel contents and specifically bile acids may be a suppressive component, hindering the antifungal effects of echinocandins. This novel exploration sheds light on the poor oral bioavailability of echinocandins. The findings imply that echinocandins alone, regardless of administration route, may not be optimal for gastrointestinal (GI) fungal infections or invasive fungal infections originating from intestinal translocation. Further clinical investigations are warranted to validate and expand upon these observations.

Extracellular and intracellular antiviral effects of ultraviolet A against severe acute respiratory syndrome coronavirus-2 are variant-independent.

Under controlled settings, narrow-band ultraviolet A (UVA) exposure exerts antiviral effects both in vivo and in vitro. The effect is thought to be mediated via direct effect on viral particles and indirectly, by modulation of metabolic pathways of host cells. We aimed to explore the extracellular and intracellular antiviral effects of UVA exposure against Alpha, Beta, and Delta variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Vero E6 kidney normal epithelial cells and human tracheal epithelial cells were infected with Alpha, Beta, and Delta variants in a BSL-3 laboratory. To assess extracellular effects, SARS-CoV-2 variants were directly exposed to a single dose of UVA prior to infection of the host cells (Vero E6 kidney normal epithelial cells and human tracheal epithelial cells) The intracellular effects of UVA were assessed by first infecting the cells with SARS-CoV-2 variants followed by UVA treatment of infected cell monolayers. Efficacy was quantified by both plaque reduction assay and quantitative real-time polymerase chain reaction. Additionally, transcriptomic analysis was performed on exposed Vero E6 cells to assess differentially expressed genes and canonical pathways as compared to controls. RESULTS: SARS-CoV-2 Alpha, Beta and Delta variants are susceptible to UVA exposure prior to infection of Vero E6 cells. Importantly, the UVA-driven reduction in Delta variant load could be reproduced in human primary tracheal cells. Beta and Delta variants load also significantly decreased during Vero E6 cells intracellular experiments. UVA-driven reductions in viral loads ameliorate several host metabolic pathways, including canonical pathways related to viral infection and interferon signaling. CONCLUSION: Narrow-band UVA exhibits both extracellular effects on SARS-CoV-2 viral particles and intracellular effects on infected cells with SARS-CoV-2. Efficacy appears to be variant independent.

Comparing the Interobserver Reliability of 4 Methods Used to Measure Knee Laxity on Coronal Plane Stress Radiograph.

Background: Varus and valgus knee stress radiographs provide valuable information in the pre- and postoperative evaluation of joint laxity in patients with multiligament knee injuries (MLKIs). Purpose: To review the literature for described techniques of quantifying laxity on coronal stress radiographs of the knee and identify the most reliable method. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: A thorough literature search using the MEDLINE and Embase databases identified 4 studies with distinct methods for objectively measuring laxity on varus and valgus stress radiographs: Heesterbeek et al (2008), Jacobsen (1976), LaPrade et al (2004), and Sawant et al (2004). To compare these methods, 200 coronal plane stress radiographs from 50 patients with MLKIs were retrospectively reviewed from an MLKI database at a single institution. The amount of varus and valgus laxity on each radiograph was measured independently by 4 reviewers using each method. Intraclass correlation coefficients (ICCs) with 95% CIs were calculated to assess the interobserver reliability of each method overall and the varus and valgus measurements individually. Results: For all 4 methods, the overall interobserver reliability was considered at least moderate. The method by Heesterbeek et al proved to have the highest interrater reliability in all domains-overall (ICC, 0.87 [95% CI, 0.85-0.90]), valgus (ICC, 0.83 [95% CI, 0.78-0.88]), and varus (ICC, 0.87 [95% CI, 0.83-0.90])-demonstrating good to excellent reliability both overall and in varus measurements and showing good reliability in valgus measurements. The method by Sawant et al demonstrated good reliability in valgus measurements. All other measures demonstrated moderate reliability. Conclusion: Available methods for measuring knee joint laxity on varus and valgus knee stress radiographs in patients with MLKIs demonstrated moderate to good interobserver reliability. The method described by Heesterbeek et al proved to have the highest reliability overall as well as in measurements on varus and valgus views individually.

Symptomatic Response to Antibiotics in Patients With Small Intestinal Bacterial Overgrowth: A Systematic Review and Meta-analysis.

Background/Aims: We performed a systematic review and meta-analysis evaluating the symptomatic response rate to antibiotics in patients with small intestinal bacterial overgrowth (SIBO). Similarly, we performed a meta-analysis on the symptomatic response to antibiotics in irritable bowel syndrome (IBS) patients with and without SIBO. Methods: MEDLINE, EMBASE, Web of Science, and Cochrane databases were searched from inception to March 2021. Randomized controlled trials and prospective studies reporting dichotomous outcomes were included. Results: There were 6 studies included in the first meta-analysis comparing the efficacy of antibiotics to placebo or no antibiotic. This included 196 patients, of whom 101 received antibiotics and 95 received placebo or no antibiotics. Significantly more patients improved with antibiotics (relative risk [95% CI] = 2.46 [1.33-4.55], P = 0.004). There were 4 studies included in the analysis comparing symptomatic response rates in IBS patients with or without SIBO with 266 IBS patients, of whom 172 had SIBO and 94 did not. The pooled response rate for symptomatic response was 51.2% in the SIBO group vs 23.4% in the no SIBO group, respectively. Significantly more IBS patients with SIBO responded to antibiotics compared to those without SIBO (relative risk [95% CI] = 2.07 [1.40-3.08], P = 0.0003). Conclusions: Antibiotics appear to be efficacious in treating SIBO, although small sample sizes and poor data quality limit this interpretation. Symptomatic response rates also appear to be higher in IBS patients with SIBO. This may be the first example of precision medicine in IBS as opposed to our current empiric treatment approach. Large-multicenter studies are needed to verify the results.

Defining Small Intestinal Bacterial Overgrowth by Culture and High Throughput Sequencing.

BACKGROUND& AIMS: Despite accelerated research in small intestinal bacterial overgrowth (SIBO), questions remain regarding optimal diagnostic approaches and definitions. Here, we aim to define SIBO using small bowel culture and sequencing, identifying specific contributory microbes, in the context of gastrointestinal symptoms. METHODS: Subjects undergoing esophagogastroduodenoscopy (without colonoscopy) were recruited and completed symptom severity questionnaires. Duodenal aspirates were plated on MacConkey and blood agar. Aspirate DNA was analyzed by 16S ribosomal RNA and shotgun sequencing. Microbial network connectivity for different SIBO thresholds and predicted microbial metabolic functions were also assessed. RESULTS: A total of 385 subjects with <103 colony forming units (CFU)/mL on MacConkey agar and 98 subjects with ≥103 CFU/mL, including ≥103 to <105 CFU/mL (N = 66) and ≥105 CFU/mL (N = 32), were identified. Duodenal microbial α-diversity progressively decreased, and relative abundance of Escherichia/Shigella and Klebsiella increased, in subjects with ≥103 to <105 CFU/mL and ≥105 CFU/mL. Microbial network connectivity also progressively decreased in these subjects, driven by the increased relative abundance of Escherichia (P < .0001) and Klebsiella (P = .0018). Microbial metabolic pathways for carbohydrate fermentation, hydrogen production, and hydrogen sulfide production were enhanced in subjects with ≥103 CFU/mL and correlated with symptoms. Shotgun sequencing (N = 38) identified 2 main Escherichia coli strains and 2 Klebsiella species representing 40.24% of all duodenal bacteria in subjects with ≥103 CFU/mL. CONCLUSIONS: Our findings confirm ≥103 CFU/mL is the optimal SIBO threshold, associated with gastrointestinal symptoms, significantly decreased microbial diversity, and network disruption. Microbial hydrogen- and hydrogen sulfide-related pathways were enhanced in SIBO subjects, supporting past studies. Remarkably few specific E coli and Klebsiella strains/species appear to dominate the microbiome in SIBO, and correlate with abdominal pain, diarrhea, and bloating severities.

Hydrogen Sulfide Producers Drive a Diarrhea-Like Phenotype and a Methane Producer Drives a Constipation-Like Phenotype in Animal Models.

BACKGROUND: We recently demonstrated that diarrhea-predominant irritable bowel syndrome (IBS-D) subjects have higher relative abundance (RA) of hydrogen sulfide (H2S)-producing Fusobacterium and Desulfovibrio species, and constipation-predominant IBS (IBS-C) subjects have higher RA of methanogen Methanobrevibacter smithii. AIMS: In this study, we investigate the effects of increased methanogens or H2S producers on stool phenotypes in rat models. METHODS: Adult Sprague-Dawley rats were fed high-fat diet (HFD) for 60 days to increase M. smithii levels, then gavaged for 10 days with water (controls) or methanogenesis inhibitors. To increase H2S producers, rats were gavaged with F. varium or D. piger. Stool consistency (stool wet weight (SWW)) and gas production were measured. 16S rRNA gene sequencing was performed on stool samples. RESULTS: In HFD diet-fed rats (N = 30), stool M. smithii levels were increased (P < 0.001) after 52 days, correlating with significantly decreased SWW (P < 0.0001) at 59 days (R = - 0.38, P = 0.037). Small bowel M. smithii levels decreased significantly in lovastatin lactone-treated rats (P < 0.0006), and SWW increased (normalized) in lovastatin hydroxyacid-treated rats (P = 0.0246), vs. controls (N = 10/group). SWW increased significantly in D. piger-gavaged rats (N = 16) on day 10 (P < 0.0001), and in F. varium-gavaged rats (N = 16) at all timepoints, vs. controls, with increased stool H2S production. 16S sequencing revealed stool microbiota alterations in rats gavaged with H2S producers, with higher relative abundance (RA) of other H2S producers, particularly Lachnospiraceae and Bilophila in F. varium-gavaged rats, and Sutterella in D. piger-gavaged rats. CONCLUSIONS: These findings suggest that increased M. smithii levels result in a constipation-like phenotype in a rat model that is partly reversible with methanogenesis inhibitors, whereas gavage with H2S producers D. piger or F. varium results in increased colonization with other H2S producers and diarrhea-like phenotypes. This supports roles for the increased RA of methanogens and H2S producers identified in IBS-C and IBS-D subjects, respectively, in contributing to stool phenotypes.

Cytolethal distending toxin B inoculation leads to distinct gut microtypes and IBS-D-like microRNA-mediated gene expression changes in a rodent model.

Diarrhea-predominant irritable bowel syndrome (IBS-D), associated with increased intestinal permeability, inflammation, and small intestinal bacterial overgrowth, can be triggered by acute gastroenteritis. Cytolethal distending toxin B (CdtB) is produced by gastroenteritis-causing pathogens and may underlie IBS-D development, through molecular mimicry with vinculin. Here, we examine the effects of exposure to CdtB alone on gut microbiome composition, host intestinal gene expression, and IBS-D-like phenotypes in a rat model. CdtB-inoculated rats exhibited increased anti-CdtB levels, which correlated with increased stool wet weights, pro-inflammatory cytokines (TNFα, IL2) and predicted microbial metabolic pathways including inflammatory responses, TNF responses, and diarrhea. Three distinct ileal microbiome profiles (microtypes) were identified in CdtB-inoculated rats. The first microtype (most like controls) had altered relative abundance (RA) of genera Bifidobacterium, Lactococcus, and Rothia. The second had lower microbial diversity, higher Escherichia-Shigella RA, higher absolute E. coli abundance, and altered host ileal tissue expression of immune-response and TNF-response genes compared to controls. The third microtype had higher microbial diversity, higher RA of hydrogen sulfide (H2S)-producer Desulfovibrio, and increased expression of H2S-associated pain/serotonin response genes. All CdtB-inoculated rats exhibited decreased ileal expression of cell junction component mRNAs, including vinculin-associated proteins. Significantly, cluster-specific microRNA-mRNA interactions controlling intestinal permeability, visceral hypersensitivity/pain, and gastrointestinal motility genes, including several previously associated with IBS were seen. These findings demonstrate that exposure to CdtB toxin alone results in IBS-like phenotypes including inflammation and diarrhea-like stool, decreased expression of intestinal barrier components, and altered ileal microtypes that influenced changes in microRNA-modulated gene expression and predicted metabolic pathways consistent with specific IBS-D symptoms.

Real-Life Patient Educational Recording Before Esophageal Manometry.

High-resolution esophageal manometry (HREM) is a fundamental diagnostic tool in esophagology. Educational tools for this procedure have remained scarce. This quality improvement project aimed to develop an enhanced digital recording about HREM and assess the effect on patient knowledge, anxiety, satisfaction, and procedure abortion rates. The Institute for Healthcare Improvement Model for Improvement and the self-regulation theory guided this project. An interprofessional team was formed. A video recording of the pre-, peri-, and post-HREM care was created. Participants were recruited in the following four cycles: Baseline, Workstation, Manometry, and Home. Questionnaires were collected pre- and postvideo education. The results demonstrated a significant increase in knowledge from 60% to 96% ( p < .001), 58% to 96% ( p < .001), 79% to 96% ( p < .001), and 92% to 97% ( p = .02) and reductions in anxiety from 7.1 to 5.5 ( p = .003), 7.6 to 6.1 ( p = .003), 7.1 to 6.5 ( p < .001), and 6.4 to 6.1 ( p = .03) in all four groups. Almost all (99.5%) participants liked the recorded education and only 2.6% of cases were aborted during the 1-year project implementation period from June 2020 to May 2021. Findings from this project support the positive impact of recorded patient education. An educational recording is standardized and has the potential to be implemented in variable settings.

Consuming artificial sweeteners may alter the structure and function of duodenal microbial communities.

Studies using stool samples suggest that non-sugar sweetener (NSS) consumption affects gut microbiome composition. However, stool does not represent the entire gut. We analyzed the duodenal luminal microbiome in subjects consuming non-aspartame non-sugar sweeteners (NANS, N = 35), aspartame only (ASP, N = 9), and controls (CON, N = 55) and the stool microbiome in a subset (N = 40). Duodenal alpha diversity was decreased in NANS vs. CON. Duodenal relative abundance (RA) of Escherichia, Klebsiella, and Salmonella (all phylum Proteobacteria) was lower in both NANS and ASP vs. CON, whereas stool RA of Escherichia, Klebsiella, and Salmonella was increased in both NANS and ASP vs. CON. Predicted duodenal microbial metabolic pathways altered in NANS vs. CON included polysaccharides biosynthesis and D-galactose degradation, whereas cylindrospermopsin biosynthesis was significantly enriched in ASP vs. CON. These findings suggest that consuming non-sugar sweeteners may significantly alter microbiome composition and function in the metabolically active small bowel, with different alterations seen in stool.

An in-depth investigation of the impact of salt nature on the formulation of microemulsion systems.

Electrolytes have a wide range of technological applications. Despite the recent improvements in characterizing and predicting the phase behavior of microemulsion systems by hydrophilic-lipophilic deviation (HLD) and net-average curvature (NAC) frameworks, they are ineffective in the presence of different salts. This work seeks to bridge this gap by investigating the influence of salt nature on the microemulsion phase formulation. First, a one-dimensional salinity scan on different microemulsion systems consisting of sodium dodecyl benzene sulfonate as a surfactant, hexane as an oil and, several brines was carried out, and the effect of each salt on the phase behavior were precisely evaluated. The results for optimum salinity and solubilization parameter of different salts were consistent with the Hofmeister series. In addition, multiple linear regression model is presented to accurately predicting the optimum salinity of different salts using this research data and all the available experimental data. The results revealed that the values estimated by this model is in significant consistency with the experimental data by correlation coefficient of 0.92. Finally, the effect of salt type on the NAC parameters (length parameter, and characteristic length[Formula: see text] were evaluated to improve the predicting ability of this equation of state in the presence of various salts. We found that salt nature has a significant impact on both these parameters. It was found that the length parameter is linearly dependent on the optimum ionic strength of salts while the salting-out capacity of each salt was predominant factor affecting the characteristic length.

Pros and Cons of Breath Testing for Small Intestinal Bacterial Overgrowth and Intestinal Methanogen Overgrowth.

Breath testing is the most widely utilized modality to diagnose small intestinal bacterial overgrowth (SIBO) and/or intestinal methanogen overgrowth (IMO). Although SIBO can be diagnosed with small bowel aspiration and breath testing, IMO can only be diagnosed with breath testing in clinical practice. Breath testing can tailor antibiotic therapy and predict response to treatment; however, the test is limited by its indirect method of measurement and concerns about the variability of orocecal transit time. Like any clinical test, breath testing has inherent strengths and limitations, and results must be interpreted with consideration of the clinical context and influencing factors. Recent studies have demonstrated the expanding clinical utility of breath testing in the diagnosis, management, and prediction of treatment response in SIBO and particularly in IMO along with the identification of distinct breath test patterns such as flat-line and high baseline hydrogen. This article reviews the strengths and limitations of breath testing in diagnosing SIBO and IMO as well as its expanding utility in clinical practice.