The clinical evidence for postbiotics as microbial therapeutics.

An optimally operating microbiome supports protective, metabolic, and immune functions, but disruptions produce metabolites and toxins which can be involved in many conditions. Probiotics have the potential to manage these. However, their use in vulnerable people is linked to possible safety concerns and maintaining their viability is difficult. Interest in postbiotics is therefore increasing. Postbiotics contain inactivated microbial cells or cell components, thus are more stable and exert similar health benefits to probiotics. To review the evidence for the clinical benefits of postbiotics in highly prevalent conditions and consider future potential areas of benefit. There is growing evidence revealing the diverse clinical benefits of postbiotics in many prevalent conditions. Postbiotics could offer a novel therapeutic approach and may be a safer alternative to probiotics. Establishing interaction mechanisms between postbiotics and commensal microorganisms will improve the understanding of potential clinical benefits and may lead to targeted postbiotic therapy.

Bacillus clausii for Gastrointestinal Disorders: A Narrative Literature Review.

The gut microbiota is intrinsically linked to human health; disturbances in microbial homeostasis are implicated in both intestinal and extraintestinal disorders. Probiotics are "live microorganisms that, when administered in adequate amounts, confer a health benefit on the host," and many commercial preparations comprising a diverse range of species are available. While probiotics have been much researched, better understanding of the probiotic effects and applications of species such as Bacillus clausii is warranted. In this narrative literature review, we review the characteristics and mechanisms of action supporting B. clausii as a probiotic and discuss the evidence from clinical studies evaluating B. clausii probiotics for the management of a variety of gastrointestinal disorders and symptoms in children and adults. Finally, we highlight the challenges of future research and the need for more robust and diverse clinical evidence to guide physicians in the clinical application of probiotics for gastrointestinal disorders and other conditions.

Current Progress and Future Perspectives on the Use of Bacillus clausii

Bacillus clausii is a probiotic that benefits human health. Its key characteristics include the ability to form spores; the resulting tolerance to heat, acid, and salt ensures safe passage through the human gastrointestinal tract with no loss of cells. Although B. clausii has been widely used for many decades, the beneficial properties of other probiotics, such as Lactobacillus spp. and Bifidobacterium spp., are better disseminated in the literature. In this review, we summarize the physiological, antimicrobial, and immunomodulatory properties of probiotic B. clausii strains. We also describe findings from studies that have investigated B. clausii probiotics from the perspective of quality and safety. We highlight innovative properties based on biochemical investigations of non-probiotic strains of B. clausii, revealing that B. clausii may have further health benefits in other therapeutic areas.

Probiotic improves symptomatic and viral clearance in Covid19 outpatients: a randomized, quadruple-blinded, placebo-controlled trial.

Intestinal bacteria may influence lung homeostasis via the gut-lung axis. We conducted a single-center, quadruple-blinded, randomized trial in adult symptomatic Coronavirus Disease 2019 (Covid19) outpatients. Subjects were allocated 1:1 to probiotic formula (strains Lactiplantibacillus plantarum KABP022, KABP023, and KAPB033, plus strain Pediococcus acidilactici KABP021, totaling 2 × 109 colony-forming units (CFU)) or placebo, for 30 days. Co-primary endpoints included: i) proportion of patients in complete symptomatic and viral remission; ii) proportion progressing to moderate or severe disease with hospitalization, or death; and iii) days on Intensive Care Unit (ICU). Three hundred subjects were randomized (median age 37.0 years [range 18 to 60], 161 [53.7%] women, 126 [42.0%] having known metabolic risk factors), and 293 completed the study (97.7%). Complete remission was achieved by 78 of 147 (53.1%) in probiotic group compared to 41 of 146 (28.1%) in placebo (RR: 1.89 [95 CI 1.40-2.55]; P < .001), significant after multiplicity correction. No hospitalizations or deaths occurred during the study, precluding the assessment of remaining co-primary outcomes. Probiotic supplementation was well-tolerated and reduced nasopharyngeal viral load, lung infiltrates and duration of both digestive and non-digestive symptoms, compared to placebo. No significant compositional changes were detected in fecal microbiota between probiotic and placebo, but probiotic supplementation significantly increased specific IgM and IgG against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) compared to placebo. It is thus hypothesized this probiotic primarily acts by interacting with the host's immune system rather than changing colonic microbiota composition. Future studies should replicate these findings and elucidate its mechanism of action (Registration: NCT04517422).Abbreviations: AE: Adverse Event; BMI: Body Mass Index; CONSORT: CONsolidated Standards of Reporting Trials; CFU: Colony-Forming Units; eDRF: Electronic Daily Report Form; GLA: Gut-Lung Axis; GSRS: Gastrointestinal Symptoms Rating Scale; hsCRP: High-sensitivity C-Reactive Protein; HR: Hazard Ratio; ICU: Intensive Care Unit; OR: Odds Ratio; PCoA: Principal Coordinate Analysis; RR: Relative Risk; RT-qPCR: Real-Time Quantitative Polymerase Chain Reaction; SARS-CoV2: Severe acute respiratory syndrome coronavirus 2; SpO2: Peripheral Oxygen Saturation; WHO: World Health Organization.

Dietary fiber and the microbiota: A narrative review by a group of experts from the Asociación Mexicana de Gastroenterología.

Dietary fiber intake is one of the most influential and efficacious strategies for modulating the gut microbiota. Said fiber can be digested by the microbiota itself, producing numerous metabolites, which include the short-chain fatty acids (SCFAs). SCFAs have local and systemic functions that impact the composition and function of the gut microbiota, and consequently, human health. The aim of the present narrative review was to provide a document that serves as a frame of reference for a clear understanding of dietary fiber and its direct and indirect effects on health. The direct benefits of dietary fiber intake can be dependent on or independent of the gut microbiota. The use of dietary fiber by the gut microbiota involves several factors, including the fiber's physiochemical characteristics. Dietary fiber type influences the gut microbiota because not all bacterial species have the same capacity to produce the enzymes needed for its degradation. A low-fiber diet can affect the balance of the SCFAs produced. Dietary fiber indirectly benefits cardiometabolic health, digestive health, certain functional gastrointestinal disorders, and different diseases.

Efficacy and safety of novel probiotic formulation in adult Covid19 outpatients: a randomized, placebo-controlled clinical trial

BackgroundProbiotics have been proposed as adjuvants for Coronavirus Disease 2019 (Covid19) but randomized controlled trials (RCT) are lacking. MethodsSingle-center, quadruple-blinded RCT. Symptomatic Covid 19 outpatients (aged 18 to 60 years) with positive SARS-CoV2 nucleic acids test were randomized to active (n=150; [≥]2x109 colony-forming units (CFU) of probiotic strains Lactiplantibacillus plantarum KABP022, KABP023 and KAPB033, plus strain Pediococcus acidilactici KABP021) or placebo (n=150), take orally once daily for 30 days. Oral acetaminophen was allowed and controlled as co-intervention. Primary endpoint included: i) proportion of patients in complete remission (both symptoms and nucleic acids test) or progressing to moderate or severe disease with hospitalization; ii) death rate and duration on Intensive Care Unit (ICU). Safety was assessed in all patients. This study is registered at ClinicalTrials.gov (NCT04517422). Findings300 subjects were randomized (median age 37.0 years [range 18 to 60], 161 [53.7%] women, 126 [42.0%] having known metabolic risk factors), and 293 completed the study (97.7%). Remission was achieved by 78 of 147 (53.1%) in the active group compared to 41 of 146 (28.1%) in placebo (P<0.0001; ARR=25.0% [95%CI 14.1-35.9%]), still significant after multiplicity correction for the primary endpoint. No hospitalizations or deaths occurred during the study, precluding the assessment of efficacy on these endpoints. No serious adverse events occurred during the study. Replication studies with this probiotic formula are warranted.

Review of the scientific evidence and technical opinion on noncaloric sweetener consumption in gastrointestinal diseases. / Revisión de la evidencia científica y opinión técnica sobre el consumo de edulcorantes no calóricos en enfermedades gastrointestinales.

The present review of noncaloric sweeteners (NCSs) by the Asociación Mexicana de Gastroenterología was carried out to analyze and answer some of the most frequent questions and concerns about NCS consumption in patients with gastrointestinal disorders, through a thorough review of the medical literature. A group of gastroenterologists and experts on nutrition, toxicology, microbiology, and endocrinology reviewed and analyzed the published literature on the topic. The working group formulated conclusions, based on the scientific evidence published, to give an opinion with respect to NCS ingestion. Current evidence does not confirm the carcinogenic potential of NCSs. However, the studies analyzed showed that saccharin could have a proinflammatory effect and that polyols can cause gastrointestinal symptoms and manifestations, depending on the dose and type of compound. The ingestion of xylitol, erythritol, sucralose, aspartame, acesulfame K, and saccharin could increase the secretion of the gastrointestinal hormones that regulate intestinal motility, and stevia and its derivatives could have a favorable effect on the percentage of liver fat. Caution should be taken in recommending aspartame consumption in patients with chronic liver disease because it reduces the ratio of branched-chain amino acids to aromatic amino acids. In addition, NCS ingestion could modify the composition of the intestinal microbiota, having an effect on gastrointestinal symptoms and manifestations. It is important to continue conducting causality studies on humans to be able to establish recommendations on NSC consumption.

The Mexican consensus on non-cardiac chest pain. / Consenso mexicano sobre dolor torácico no cardiaco.

INTRODUCTION: Non-cardiac chest pain is defined as a clinical syndrome characterized by retrosternal pain similar to that of angina pectoris, but of non-cardiac origin and produced by esophageal, musculoskeletal, pulmonary, or psychiatric diseases. AIM: To present a consensus review based on evidence regarding the definition, epidemiology, pathophysiology, and diagnosis of non-cardiac chest pain, as well as the therapeutic options for those patients. METHODS: Three general coordinators carried out a literature review of all articles published in English and Spanish on the theme and formulated 38 initial statements, dividing them into 3 main categories: (i)definitions, epidemiology, and pathophysiology; (ii)diagnosis, and (iii)treatment. The statements underwent 3rounds of voting, utilizing the Delphi system. The final statements were those that reached >75% agreement, and they were rated utilizing the GRADE system. RESULTS AND CONCLUSIONS: The final consensus included 29 statements. All patients presenting with chest pain should initially be evaluated by a cardiologist. The most common cause of non-cardiac chest pain is gastroesophageal reflux disease. If there are no alarm symptoms, the initial approach should be a therapeutic trial with a proton pump inhibitor for 2-4weeks. If dysphagia or alarm symptoms are present, endoscopy is recommended. High-resolution manometry is the best method for ruling out spastic motor disorders and achalasia and pH monitoring aids in demonstrating abnormal esophageal acid exposure. Treatment should be directed at the pathophysiologic mechanism. It can include proton pump inhibitors, neuromodulators and/or smooth muscle relaxants, psychologic intervention and/or cognitive therapy, and occasionally surgery or endoscopic therapy.

Consensus on the prevention, diagnosis, and treatment of Clostridium difficile infection. / Consenso sobre prevención, diagnóstico y tratamiento de la infección por Clostridium difficile.

In recent decades, Clostridium difficile infection (CDI) has become a worldwide health problem. Mexico is no exception, and therefore the Asociación Mexicana de Gastroenterología brought together a multidisciplinary group (gastroenterologists, endoscopists, internists, infectious disease specialists, and microbiologists) to carry out the "Consensus on the prevention, diagnosis, and treatment of Clostridium difficile infection", establishing useful recommendations (in relation to the adult population) for the medical community. Said recommendations are presented herein. Among them, it was recognized that CDI should be suspected in subjects with diarrhea that have a history of antibiotic and/or immunosuppressant use, but that it can also be a community-acquired infection. A 2-step diagnostic algorithm was proposed, in which a highly sensitive test, such as glutamate dehydrogenase (GDH), is first utilized, and if positive, confirmed by the detection of toxins through immunoassay or nucleic acid detection tests. Another recommendation was that CDI based on clinical evaluation be categorized as mild-moderate, severe, and complicated severe, given that such a classification enables better therapeutic decisions to be made. In mild-moderate CDI, oral vancomycin is the medication of choice, and metronidazole is recommended as an alternative treatment. In addition, fecal microbiota transplantation was recognized as an efficacious option in patients with recurrence or in the more severe cases of infection, and surgery should be reserved for patients with severe colitis (toxic megacolon), in whom all medical treatment has failed.

Finding hens in a haystack: Consistency of movement patterns within and across individual laying hens maintained in large groups.

We sought to objectively quantify and compare the recorded movement and location patterns of laying hens within a commercial system. Using a custom tracking system, we monitored the location within five zones of a commercial aviary for 13 hens within a flock of 225 animals for a contiguous period of 11 days. Most hens manifested a hen-specific pattern that was (visually) highly consistent across days, though, within that consistency, manifested stark differences between hens. Three different methods were used to classify individual daily datasets into groups based on their similarity: (i) Linear Discriminant Analysis based on six summary variables (transitions into each zone) and total transitions; (ii) Hierarchical Clustering, a naïve clustering analysis technique, applied to summary variables and iii) Hierarchical Clustering applied to dissimilarity matrices produced by Dynamic Time Warping. The three methods correctly classified more than 85% of the hen days and provided a unique means to assess behaviour of a system indicating a considerable degree of complexity and structure. We believe the current effort is the first to document these location and movement patterns within a large, complex commercial system with a large potential to influence the assessment of animal welfare, health, and productivity.

Experiencia clínica con un simbiótico (Bifidobacterium longum AW11- Fos cc. Actilight) en el alivio del estreñimiento y otros síntomas digestivos / Clinical experience with a synbiotic (Bifidobacterium longum AW11- Fos cc. Actilight) in the relieve of constipation and other digestive symptoms

Resumen: ANTECEDENTES: el estreñimiento, la distensión y el dolor abdominales son muy prevalentes en la población general y representan un reto terapéutico. Los probióticos han mostrado ser efectivos en el control de estos síntomas. OBJETIVO: investigar la utilidad clínica de la administración del simbiótico Bifidobacterium longum AW11 (5x109 UFC) y fructo-oligosacáridos de cadena corta (Fos cc. Actilight 2.5 g) en el alivio del estreñimiento y otros síntomas digestivos. PACIENTES Y MÉTODO: estudio abierto observacional en el que se incluyeron pacientes con síntomas digestivos de más de seis meses de evolución, sin enfermedad orgánica que explicara sus síntomas y que recibieron tratamiento con el simbiótico, un sobre diario durante ocho semanas. La intensidad y frecuencia de los síntomas se evaluaron mediante un cuestionario y las características de las evacuaciones mediante la escala de Bristol al inicio, a las cuatro y a las ocho semanas de tratamiento. RESULTADOS: se incluyeron 361 pacientes con síntomas digestivos. El promedio de la duración de los síntomas fue de 2.3±4.9 años, 96% tenía estreñimiento, 79% cumplió con criterios de síndrome de intestino irritable y 16% de estreñimiento funcional (Roma III). El número de evacuaciones semanales se incrementó de 3.8±3.3 iniciales a 5.9±3.0 en la semana 8 (p<0.00001). También mejoraron significativamente: el número de evacuaciones espontáneas completas, la consistencia de las heces (escala de Bristol) y la sensación global de bienestar y disminuyeron significativamente el esfuerzo al defecar, la distensión abdominal subjetiva, la frecuencia de dolor abdominal y la sensación de malestar abdominal. La proporción de pacientes totalmente satisfechos se incrementó de 6% al inicio a 78% en la semana 8. CONCLUSIONES: la administración diaria del simbiótico con B. longum y Fos cc. es eficaz para aliviar el estreñimiento y el dolor y la distensión abdominales.

Abstract: BACKGROUND: Constipation, abdominal pain and bloating are highly prevalent in general population and they constitute a therapeutic challenge. Probiotics are effective in the management of these symptoms. OBJECTIVE: To investigate in daily clinical practice if the administration of a supplement food containing Bifidobacterium longum AW11 (5x109 FCU) and short chain fructo-oligosaccharides (Fos cc. Actilight 2.5g) can relieve constipation and functional bowel symptoms. PATIENTS AND METHOD: An open and observational study was done including patients with digestive symptoms of more than six months of evolution, without organic disease explaining their symptoms and who received treatment with the synbiotic, daily during eight weeks. Intensity and frequency of symptoms were assessed by a questionnaire and the characteristics of evacuations by Bristol's scale at baseline and after four and eight weeks of treatment. RESULTS: There were included 361 patients with digestive symptoms lasting 2.3±4.9 years; 96% had constipation, 79% fulfilled Rome III criteria for irritable bowel syndrome an 16% for functional constipation. Treatment with the synbiotic increased frequency of bowel movements per week from 3.8±3.3 to 5.9±3.0 at week 8 (p<0.00001). There was a significant improvement also for: complete spontaneous bowel movements, stool consistency (Bristol scale), straining, bloating, frequency of abdominal pain, malaise, and global wellness. Percentage of patients with complete satisfaction increased from 6% in the initial visit to 78% at the week 8. CONCLUSIONS: Daily ingestion of a synbiotic (B. longum and Fos cc.) is effective to relieve constipation, abdominal pain and bloating.

Inter-observer agreement for diagnostic classification of esophageal motility disorders defined in high-resolution manometry.

High-resolution esophageal manometry (HRM) is a recent development used in the evaluation of esophageal function. Our aim was to assess the inter-observer agreement for diagnosis of esophageal motility disorders using this technology. Practitioners registered on the HRM Working Group website were invited to review and classify (i) 147 individual water swallows and (ii) 40 diagnostic studies comprising 10 swallows using a drop-down menu that followed the Chicago Classification system. Data were presented using a standardized format with pressure contours without a summary of HRM metrics. The sequence of swallows was fixed for each user but randomized between users to avoid sequence bias. Participants were blinded to other entries. (i) Individual swallows were assessed by 18 practitioners (13 institutions). Consensus agreement (≤ 2/18 dissenters) was present for most cases of normal peristalsis and achalasia but not for cases of peristaltic dysmotility. (ii) Diagnostic studies were assessed by 36 practitioners (28 institutions). Overall inter-observer agreement was 'moderate' (kappa 0.51) being 'substantial' (kappa > 0.7) for achalasia type I/II and no lower than 'fair-moderate' (kappa >0.34) for any diagnosis. Overall agreement was somewhat higher among those that had performed >400 studies (n = 9; kappa 0.55) and 'substantial' among experts involved in development of the Chicago Classification system (n = 4; kappa 0.66). This prospective, randomized, and blinded study reports an acceptable level of inter-observer agreement for HRM diagnoses across the full spectrum of esophageal motility disorders for a large group of clinicians working in a range of medical institutions. Suboptimal agreement for diagnosis of peristaltic motility disorders highlights contribution of objective HRM metrics.

[Guidelines for diagnosis and treatment of constipation in Mexico. B) Diagnostic approach]. / Guías de diagnóstico y tratamiento del estreñimiento en México. B) Abordaje diagnóstico.

BACKGROUND: Constipation is a heterogeneous symptom so an accurate diagnosis requires an appropriate approach. OBJECTIVE AND METHODS: To establish the clinical guidelines for diagnosis and treatment of chronic constipation in Mexico we have reviewed the diagnostic aspects of constipation according to the availability of resources in our country. In addition, evidence-based recommendations have been provided. RESULTS: The symptoms that best define constipation in our population are infrequent stool, hard stool expulsion, excessive effort and sensation of incomplete evacuation. Digital rectal examination is a useful diagnostic tool to discard organic diseases and pelvic floor dyssynergia. Patients with risk factors such as recent onset of constipation, family history of inflammatory bowel disease or colon cancer and those with alarm signs (unintentional weight loss and significant anemia, blood in stool) should undergo endoscopic diagnostic studies. If they are available, the most useful tests in evaluating patients with functional constipation are colonic transit with radiopaque markers and anorectal manometry with balloon expulsion test. CONCLUSIONS: Patients with symptoms of chronic constipation should undergo advanced colorectal physiological studies to try to establish the cause of constipation.

[Differences between Chicago and traditional classifications in the diagnosis of esophageal motor disorders with high-resolution manometry and topography of esophageal pressure]. / Diferencias entre las clasificaciones de Chicago y la tradicional en el diagnóstico de los trastornos motores del esófago con manometría de alta resolución y topografía de la presión esofágica.

BACKGROUND: With the introduction of high resolution manometry (HRM) and esophageal topography a novel classification (Chicago Classification) has been proposed for the diagnosis of esophageal motor disorders (EMD). Clinical differences with the traditional classification are currently under evaluation. AIM: To investigate differences between the Chicago (CC) and traditional (TC) classifications in the diagnosis of EMD. METHODS: Consecutive patients with indication for esophageal manometry were studied. HRM was performed with a 36 sensors solid-state catheter and Manoview software (V2.0).Conventional manometric tracings were analyzed by an investigator blinded to the results of HRM. Diagnosis by CC and CT were compared. RESULTS: Two hundred patients were studied, 106 (53%) of them women (53%) with a mean patient age of 43.4 (range 16 - 84) years. Preoperative evaluation for GERD 152 (76%) was the most frequent indication. Achalasia (8), scleroderma (2) and peristaltic dysfunction (60 vs. 59) were similarly diagnosed by CC and CT. Spastic disorders were more frequently identified by CC: nutcracker esophagus (NC) in 3, spastic NC in3 and segmental NC in 11 patients versus TC: NC 5. Three patients had spasm with CC and 1 with TC. Non specific motor disorder was diagnosed by TC and 2 patients had functional obstruction with CC. Hypotensive lower esophageal sphincter was identified in 63 patients with CC vs.57 with TC. CONCLUSIONS: Spastic disorders and functional obstruction were the EMD better identified by HRM and CC.

Low levels of urinary iodine excretion in schoolchildren of rural areas in Cuba.

OBJECTIVE: We set up a baseline data on urinary iodine excretion from a nationwide representative sample of rural schoolchildren before instituting iodine supplementation. DESIGN: Stratified multistage cluster sampling in three different strata: lowlands, foothills and mountainous areas. Early morning urine samples were collected for evaluation of iodine status. SETTING: Field study in 25 municipalities in 11 out of 14 provinces. The study was carried out from October to December 1995. SUBJECTS: Three thousand and twenty-seven schoolchildren of either sex, 6 to < 12 y from 87 primary schools. RESULTS: The median urinary iodine excretion was 95 microg/L for the whole sample. The situation in a few foothills and all mountainous areas showed a moderate to severe deficiency. In the mountainous stratum, the median urinary iodine excretion values was less than 20 microg/L. CONCLUSIONS: Cuba has a mild iodine deficiency public health problem with respect to WHO criteria, which in the mountainous areas is severe. The Government of Cuba has started a national Plan of Action and funds are being mobilized to introduce nationwide iodized salt.