Can the Evidence-Based Use of Probiotics (Notably Saccharomyces boulardii CNCM I-745 and Lactobacillus rhamnosus GG) Mitigate the Clinical Effects of Antibiotic-Associated Dysbiosis?

Dysbiosis corresponds to the disruption of a formerly stable, functionally complete microbiota. In the gut, this imbalance can lead to adverse health outcomes in both the short and long terms, with a potential increase in the lifetime risks of various noncommunicable diseases and disorders such as atopy (like asthma), inflammatory bowel disease, neurological disorders, and even behavioural and psychological disorders. Although antibiotics are highly effective in reducing morbidity and mortality in infectious diseases, antibiotic-associated diarrhoea is a common, non-negligible clinical sign of gut dysbiosis (and the only visible one). Re-establishment of a normal (functional) gut microbiota is promoted by completion of the clinically indicated course of antibiotics, the removal of any other perturbing external factors, the passage of time (i.e. recovery through the microbiota's natural resilience), appropriate nutritional support, and-in selected cases-the addition of probiotics. Systematic reviews and meta-analyses of clinical trials have confirmed the strain-specific efficacy of some probiotics (notably the yeast Saccharomyces boulardii CNCM I-745 and the bacterium Lactobacillus rhamnosus GG) in the treatment and/or prevention of antibiotic-associated diarrhoea in children and in adults. Unusually for a probiotic, S. boulardii is a eukaryote and is not therefore directly affected by antibiotics-making it suitable for administration in cases of antibiotic-associated diarrhoea. A robust body of evidence from clinical trials and meta-analyses shows that the timely administration of an adequately dosed probiotic (upon initiation of antibiotic treatment or within 48 h) can help to prevent or resolve the consequences of antibiotic-associated dysbiosis (such as diarrhoea) and promote the resilience of the gut microbiota and a return to the pre-antibiotic state. A focus on the prescription of evidence-based, adequately dosed probiotics should help to limit unjustified and potentially ineffective self-medication.

Gut Microbiota Composition in Long-Remission Ulcerative Colitis is Close to a Healthy Gut Microbiota.

BACKGROUND: Microbiome studies report low gut microbial richness and diversity in ulcerative colitis (UC) patients. We explored whether UC patients who reach long-term clinical, endoscopic, and histological remission show a gut microbial ecosystem that is similar to healthy individuals. METHODS: We collected 184 stool samples from 111 individuals (UC patients in long remission, short remission, flare, and healthy control subjects). Microbiota was analyzed by amplicon sequencing (16S ribosomal RNA) and quantitative polymerase chain reaction for specific taxa. All UC remission patients were followed-up for 2 years. FINDINGS: A drop in species diversity and richness, underrepresentation of butyrate producers, and gain of potentially harmful bacteria were significantly detected in samples from disease-flare and short-remission patients. In contrast, Chao1 and Shannon indexes of diversity did not differ among patients in long remission and healthy control subjects. Long-remission patients also presented fecal bacterial composition closer to that in healthy control subjects. There was a positive correlation between Akkermansia muciniphila abundance and time in remission (rs = 0.53, P < .001). Logistic regression analysis showed that a high Shannon index (odds ratio, 4.83; 95% confidence interval, 1.5-20.6) or presence of A. muciniphila (odds ratio, 4.9; 95% confidence interval, 1.12-29.08) in fecal samples at entry was independently associated with clinical remission over a follow-up period of 24 months. INTERPRETATION: UC patients who achieve long-term remission show evidence of substantial recovery of the gut microbial ecosystem in terms of diversity and composition. Recovery may just reflect adequate control of inflammatory activity, but higher bacterial diversity or the presence of A. muciniphila in fecal samples predicts flare-free outcomes.

Microbiome studies have shown low gut microbial richness and diversity in ulcerative colitis patients. Patients who achieve long-term remission show evidence of substantial recovery of the gut microbial ecosystem in terms of diversity and composition.

Metabolic response of intestinal microbiota to guar gum consumption.

Background: Guar gum is used extensively as a thickening agent in food, but it remains uncertain whether and to what extent it is fermented by colonic microbiota and whether it has microbiota modulatory properties. Aim: To determine the metabolic response of intestinal microbiota to guar gum consumption, specifically, the extent of initial fermentation and subsequent adaptation. Methods: Single-center, single arm, open label, proof-of-concept study testing the effect of guar gum on microbiota metabolism and adaptation. Healthy male subjects (n = 12) were administered gum guar (8 g/day) for 18 days. Outcomes were measured before, at initial and late administration: (a) anal gas evacuations (number/day); (b) digestive sensations (daily scales); and (c) fecal gut microbiota taxonomy and metabolic functions by shotgun sequencing. Results: At initial consumption, guar gum induced a transient increase in anal gas evacuations and digestive sensations; gas evacuation completely reverted upon continuous administration, whereas sensations reverted only in part. Guar gum induced moderate changes in human microbiota composition at both taxonomic and functional levels. Positive associations between effects on microbiota (proliferation of Agathobaculum butyriciproducens and Lachnospira pectinoschiza) and hedonic sensations were detected. Conclusion: Guar gum is metabolized by intestinal microbiota, and, upon continuous consumption, induces a selective adaptation of microbial taxonomy and function. These data highlight the potential interest of guar gum for novel prebiotic ingredient formulation.

Effect of Resistant Dextrin on Intestinal Gas Homeostasis and Microbiota.

Previous studies have shown that a resistant dextrin soluble fibre has prebiotic properties with related health benefits on blood glucose management and satiety. Our aim was to demonstrate the effects of continuous administration of resistant dextrin on intestinal gas production, digestive sensations, and gut microbiota metabolism and composition. Healthy subjects (n = 20) were given resistant dextrin (14 g/d NUTRIOSE®, Roquette Frères, Lestrem, France) for four weeks. Outcomes were measured before, at the beginning, end, and two weeks after administration: anal evacuations of gas during daytime; digestive perception, girth, and gas production in response to a standard meal; sensory and digestive responses to a comfort meal; volume of colonic biomass by magnetic resonance; taxonomy and metabolic functions of fecal microbiota by shotgun sequencing; metabolomics in urine. Dextrin administration produced an initial increase in intestinal gas production and gas-related sensations, followed by a subsequent decrease, which magnified after discontinuation. Dextrin enlarged the volume of colonic biomass, inducing changes in microbial metabolism and composition with an increase in short chain fatty acids-producing species and modulation of bile acids and biotin metabolism. These data indicate that consumption of a soluble fibre induces an adaptative response of gut microbiota towards fermentative pathways with lower gas production.

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.

Macrogol: evaluación de la percepción de efectividad y calidad de vida en individuos con estreñimiento / Macrogol: evaluation of the perception of effectiveness and quality of life in individuals with constipation

Introducción: El estreñimiento tiene una prevalencia del 14-30% en España, su causa es multifactorial y afecta negativamente al bienestar y a la calidad de vida de las personas. Entre los tratamientos para el estreñimiento funcional se encuentran los laxantes osmóticos como Macrogol 4000. El grado de satisfacción con los laxantes es proporcional a la efectividad y mejora de la calidad de vida percibidas. Método: se realizó una encuesta en farmacias españolas a 100 consumidores que adquirían Macrogol 4000 como producto sanitario, con objeto de tratar los síntomas del estreñimiento. Se midieron los cambios en la calidad de vida y la percepción subjetiva de la efectividad a los 4, 8 y 14 días de tratamiento empleando la metodología CATI, basada en encuestas telefónicas. Resultados: Tras 14 días de consumo se observó una reducción significativa (p<0,05) del malestar físico y psicosocial. Las respuestas a los cuestionarios de percepción de efectividad mejoraron a partir del octavo día. Aumentó el acuerdo con las percepciones subjetivas de alivio del estreñimiento (81%-97%), de bienestar (90%-96%) y mejora de las sensaciones físicas (77%-97%). Al final del estudio, el 95% de los sujetos estaba satisfecho o muy satisfecho con el tratamiento elegido. Conclusiones: El uso del producto sanitario Macrogol 4000 durante 14 días mejora el malestar físico y psicosocial al mismo tiempo que se produce un incremento de la percepción de su efectividad en individuos con estreñimiento funcional. (AU)

Introduction: Constipation has a prevalence of 14-30% in Spain, its cause is multifactorial and negatively affects people’s well-being and quality of life. Treatments for functional constipation include osmotic laxatives such as Macrogol 4000. The degree of satisfaction with laxatives is proportional to the perceived effectiveness and improvement in quality of life. Method: a survey was conducted in Spanish pharmacies among 100 consumers who purchased Macrogol 4000 as a medical device, in order to treat the symptoms of constipation. Changes in quality of life and subjective perception of effectiveness were measured after 4, 8 and 14 days of treatment using CATI methodology, based on telephone surveys.Results: After 14 days of consumption, a significant reduction (p<0.05) in physical and psychosocial discomfort was observed. Responses on the effectiveness perception questionnaires improved after day 8. The number of responses expressing agreement with subjective perceptions of relief from constipation (81%-97%), of well-being (90%-96%) and of improved physical sensations (77%-97%) increased. At the end of the study, 95% of participants were satisfied or very satisfied with the chosen treatment. Conclusions: The use of Macrogol 4000 for 14 days improves physical and psychosocial discomfort at the same time as there is an increase in the perception of its effectiveness in individuals with functional constipation. (AU)

Colonic bacterial diversity and dysbiosis in active microscopic colitis as compared to chronic diarrhoea and healthy controls: effect of polyethylene glycol after bowel lavage for colonoscopy.

BACKGROUND: Most microbiota studies in microscopic colitis patients are performed after diagnostic colonoscopy without considering the potential effect of colonic lavage. Patients may achieve clinical remission after colonoscopy and it is unknown whether lavage-induced changes play a role. AIM: To assess the effect of polyethylene glycol (PEG) colonic lavage on clinical remission rate, microbial diversity, microbial dysbiosis index and specific microbial changes in patients with active microscopic colitis as compared to other diarrhoeal diseases and healthy controls. METHODS: Fifty-five consecutive patients presenting chronic watery diarrhoea and 12 healthy controls were included. Faecal samples were collected three days before and 30 days after PEG in patients and controls for microbiome analysis. RESULTS: Clinical remission was observed in 53% of microscopic colitis patients, and in 32% of non-microscopic colitis patients (p = 0.16). Considering patients with persisting diarrhoea after colonoscopy, 71% of non-microscopic colitis patients had bile acid diarrhoea. Baseline Shannon Index was lower in diarrhoea groups than in healthy controls (p = 0.0025); there were no differences between microscopic colitis, bile-acid diarrhoea and functional diarrhoea. The microbial dysbiosis index was significantly higher in microscopic colitis than in bile acid diarrhoea plus functional diarrhoea (p = 0.0095), but no bacterial species showed a significantly different relative abundance among the diarrheal groups. CONCLUSIONS: Dysbiosis is a feature in active microscopic colitis, but loss of microbial diversity was similar in all diarrheal groups, suggesting that faecal microbial changes are not due to microscopic colitis itself but associated with stool form. A considerable number of microscopic colitis patients achieved clinical remission after colonoscopy, but we were unable to demonstrate related PEG-induced changes in faecal microbiome.

Antibiotics, gut microbiota, and irritable bowel syndrome: What are the relations?

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder in which recurrent abdominal pain is associated with defecation or a change in bowel habits (constipation, diarrhea, or both), and it is often accompanied by symptoms of abdominal bloating and distension. IBS is an important health care issue because it negatively affects the quality of life of patients and places a considerable financial burden on health care systems. Despite extensive research, the etiology and underlying pathophysiology of IBS remain incompletely understood. Proposed mechanisms involved in its pathogenesis include increased intestinal permeability, changes in the immune system, visceral hypersensitivity, impaired gut motility, and emotional disorders. Recently, accumulating evidence has highlighted the important role of the gut microbiota in the development of IBS. Microbial dysbiosis within the gut is thought to contribute to all aspects of its multifactorial pathogenesis. The last few decades have also seen an increasing interest in the impact of antibiotics on the gut microbiota. Moreover, antibiotics have been suggested to play a role in the development of IBS. Extensive research has established that antibacterial therapy induces remarkable shifts in the bacterial community composition that are quite similar to those observed in IBS. This suggestion is further supported by data from cohort and case-control studies, indicating that antibiotic treatment is associated with an increased risk of IBS. This paper summarizes the main findings on this issue and contributes to a deeper understanding of the link between antibiotic use and the development of IBS.

Anti-Inflammatory Effect of an O-2-Substituted (1-3)-ß-D-Glucan Produced by Pediococcus parvulus 2.6 in a Caco-2 PMA-THP-1 Co-Culture Model.

Bacterial ß-glucans are exopolysaccharides (EPSs), which can protect bacteria or cooperate in biofilm formation or in bacterial cell adhesion. Pediococcus parvulus 2.6 is a lactic acid bacterium that produces an O-2-substituted (1-3)-ß-D-glucan. The structural similarity of this EPS to active compounds such as laminarin, together with its ability to modulate the immune system and to adhere in vitro to human enterocytes, led us to investigate, in comparison with laminarin, its potential as an immunomodulator of in vitro co-cultured Caco-2 and PMA-THP-1 cells. O-2-substituted (1-3)-ß-D-glucan synthesized by the GTF glycosyl transferase of Pediococcus parvulus 2.6 or that by Lactococcus lactis NZ9000[pGTF] were purified and used in this study. The XTT tests revealed that all ß-glucans were non-toxic for both cell lines and activated PMA-THP-1 cells' metabolisms. The O-2-substituted (1-3)-ß-D-glucan modulated production and expression of IL-8 and the IL-10 in Caco-2 and PMA-THP-1 cells. Laminarin also modulated cytokine production by diminishing TNF-α in Caco-2 cells and IL-8 in PMA-THP-1. All these features could be considered with the aim to produce function foods, supplemented with laminarin or with another novel ß-glucan-producing strain, in order to ameliorate an individual's immune system response toward pathogens or to control mild side effects in remission patients affected by inflammatory bowel diseases.

Dysbiosis and relapse-related microbiome in inflammatory bowel disease: A shotgun metagenomic approach.

Crohn's disease (CD) and ulcerative colitis (UC), the two main forms of inflammatory bowel disease (IBD), affect several million people worldwide. CD and UC are characterized by periods of clinical remission and relapse. Although IBD patients present chronic alterations of the gut microbiome, called dysbiosis, little attention has been devoted to the relapse-related microbiome. To address this gap, we generated shotgun metagenomic data from the stools of two European cohorts-134 Spanish (followed up for one year) and 49 Belgian (followed up for 6 months) subjects-to characterize the microbial taxonomic and metabolic profiles present. To assess the predictive value of microbiome data, we added the taxonomic profiles generated from a previous study of 130 Americans. Our results revealed that CD was more dysbiotic than UC compared to healthy controls (HC) and that strategies for energy extraction and propionate production were different in CD compared to UC and HC. Remarkably, CD and UC relapses were not associated with alpha- or beta-diversity, or with a dysbiotic score. However, CD relapse was linked to alterations at the species and metabolic pathway levels, including those involved in propionate production. The random forest method using taxonomic profiles allowed the prediction of CD vs. non-CD with an AUC = 0.938, UC vs. HC with an AUC = 0.646, and CD relapse vs. remission with an AUC = 0.769. Our study validates previous taxonomic findings, points to different relapse-related growth and defence mechanisms in CD compared to UC and HC and provides biomarkers to discriminate IBD subtypes and predict disease activity.

A Fermented Milk Product Containing B. lactis CNCM I-2494 Improves the Tolerance of a Plant-Based Diet in Patients with Disorders of Gut-Brain Interactions.

Healthy, plant-based diets, rich in fermentable residues, may induce gas-related symptoms. The aim of this exploratory study was to assess the effects of a fermented milk product, containing probiotics, on the tolerance of a healthy diet in patients with disorders of gut-brain interactions (DGBI), complaining of excessive flatulence. In an open design, a 3-day healthy, mostly plant-based diet was administered to patients with DGBI (52 included, 43 completed) before and at the end of 28 days of consumption of a fermented milk product (FMP) containing Bifidobacterium animalis subsp. lactis CNCM I-2494 and lactic acid bacteria. As compared to a habitual diet, the flatulogenic diet increased the perception of digestive symptoms (flatulence score 7.1 ± 1.6 vs. 5.8 ± 1.9; p < 0.05) and the daily number of anal gas evacuations (22.4 ± 12.5 vs. 16.5 ± 10.2; p < 0.0001). FMP consumption reduced the flatulence sensation score (by -1.6 ± 2.2; p < 0.05) and the daily number of anal gas evacuations (by -5.3 ± 8.2; p < 0.0001). FMP consumption did not significantly alter the overall gut microbiota composition, but some changes in the microbiota correlated with the observed clinical improvement. The consumption of a product containing B. lactis CNCM I-2494 improved the tolerance of a healthy diet in patients with DGBI, and this effect may be mediated, in part, by the metabolic activity of the microbiota.

Microbiota intestinal y salud / Gut microbes and health

El cuerpo humano está poblado por miríadas de microorganismos en toda su superficie y en las cavidades conectadas con el exterior. Los colonizadores microbianos del intestino (microbiota) son parte funcional y no prescindible del organismo humano: aportan genes (microbioma) y funciones adicionales a los recursos de nuestra especie, y participan en múltiples procesos fisiológicos (desarrollo somático, nutrición, inmunidad, etc.). Algunas enfermedades crónicas no transmisibles de la sociedad desarrollada (atopias, síndrome metabólico, enfermedades inflamatorias, cáncer y algunos trastornos de la conducta) se asocian a disbiosis: pérdida de riqueza de especies en la microbiota intestinal y desviación del entorno microbiano ancestral. Los cambios en la transmisión vertical del microbioma, el uso de antisépticos y antibióticos y los hábitos dietéticos de la sociedad industrializada parecen estar en el origen de la disbiosis. Generar y mantener diversidad en la microbiota es un nuevo objetivo clínico para la promoción de salud y la prevención de enfermedades.(AU)

The human body is populated by myriads of microorganisms throughout its surface and in the cavities connected to the outside. The microbial colonisers of the intestine (microbiota) are a functional and non-expendable part of the human organism: they provide genes (microbiome) and additional functions to the resources of our species and participate in multiple physiological processes (somatic development, nutrition, immunity, etc.). Some chronic non-communicable diseases of developed society (atopias, metabolic syndrome, inflammatory diseases, cancer and some behaviour disorders) are associated with dysbiosis: loss of species richness in the intestinal microbiota and deviation from the ancestral microbial environment. Changes in the vertical transmission of the microbiome, the use of antiseptics and antibiotics, and dietary habits in industrialised society appear to be at the origin of dysbiosis. Generating and maintaining diversity in the microbiota is a new clinical target for health promotion and disease prevention.(AU)

Differential Effects of Western and Mediterranean-Type Diets on Gut Microbiota: A Metagenomics and Metabolomics Approach.

Our aim was to determine the effect of diet on gut microbiota, digestive function and sensations, using an integrated clinical, metagenomics and metabolomics approach. We conducted a cross-over, randomised study on the effects of a Western-type diet versus a fibre-enriched Mediterranean diet. In 20 healthy men, each diet was administered for 2 weeks preceded by a 2-week washout diet. The following outcomes were recorded: (a) number of anal gas evacuations; (b) digestive sensations; (c) volume of gas evacuated after a probe meal; (d) colonic content by magnetic resonance imaging; (e) gut microbiota taxonomy and metabolic functions by shotgun sequencing of faecal samples; (f) urinary metabolites using untargeted metabolomics. As compared to a Western diet, the Mediterranean diet was associated with (i) higher number of anal gas evacuations, (ii) sensation of flatulence and borborygmi, (iii) larger volume of gas after the meal and (iv) larger colonic content. Despite the relatively little difference in microbiota composition between both diets, microbial metabolism differed substantially, as shown by urinary metabolite profiles and the abundance of microbial metabolic pathways. The effects of the diet were less evident in individuals with robust microbiotas (higher beta-diversity). To conclude, healthy individuals tolerate dietary changes with minor microbial modifications at the composition level but with remarkable variation in microbial metabolism.

Long-Term Safety and Efficacy of Prebiotic Enriched Infant Formula-A Randomized Controlled Trial.

The present study aims to evaluate the effects of an infant formula supplemented with a mixture of prebiotic short and long chain inulin-type oligosaccharides on health outcomes, safety and tolerance, as well as on fecal microbiota composition during the first year of life. In a prospective, multicenter, randomized, double-blind study, n = 160 healthy term infants under 4 months of age were randomized to receive either an infant formula enriched with 0.8 g/dL of Orafti®Synergy1 or an unsupplemented control formula until the age of 12 months. Growth, fever (>38 °C) and infections were regularly followed up by a pediatrician. Digestive symptoms, stool consistency as well as crying and sleeping patterns were recorded during one week each study month. Fecal microbiota and immunological biomarkers were determined from a subgroup of infants after 2, 6 and 12 months of life. The intention to treat (ITT) population consisted of n = 149 infants. Both formulae were well tolerated. Mean duration of infections was significantly lower in the prebiotic fed infants (p < 0.05). The prebiotic group showed higher Bifidobacterium counts at month 6 (p = 0.006), and higher proportions of Bifidobacterium in relation to total bacteria at month 2 and 6 (p = 0.042 and p = 0.013, respectively). Stools of infants receiving the prebiotic formula were softer (p < 0.05). Orafti®Synergy1 tended to beneficially impact total daily amount of crying (p = 0.0594). Supplementation with inulin-type prebiotic oligosaccharides during the first year of life beneficially modulates the infant gut microbiota towards higher Bifidobacterium levels at the first 6 months of life, and is associated with reduced duration of infections.

Gut microbes and health. / Microbiota intestinal y salud.

The human body is populated by myriads of microorganisms throughout its surface and in the cavities connected to the outside. The microbial colonisers of the intestine (microbiota) are a functional and non-expendable part of the human organism: they provide genes (microbiome) and additional functions to the resources of our species and participate in multiple physiological processes (somatic development, nutrition, immunity, etc.). Some chronic non-communicable diseases of developed society (atopias, metabolic syndrome, inflammatory diseases, cancer and some behaviour disorders) are associated with dysbiosis: loss of species richness in the intestinal microbiota and deviation from the ancestral microbial environment. Changes in the vertical transmission of the microbiome, the use of antiseptics and antibiotics, and dietary habits in industrialised society appear to be at the origin of dysbiosis. Generating and maintaining diversity in the microbiota is a new clinical target for health promotion and disease prevention.

Evaluation of an O2-Substituted (1-3)-ß-D-Glucan, Produced by Pediococcus parvulus 2.6, in ex vivo Models of Crohn's Disease.

1,3-ß-glucans are extracellular polysaccharides synthesized by microorganisms and plants, with therapeutic potential. Among them, the O2-substituted-(1-3)-ß-D-glucan, synthesized by some lactic acid bacteria (LAB), has a prebiotic effect on probiotic strains, an immunomodulatory effect on monocyte-derived macrophages, and potentiates the ability of the producer strain to adhere to Caco-2 cells differentiated to enterocytes. In this work, the O2-substituted-(1-3)-ß-D-glucan polymers produced by GTF glycoyltransferase in the natural host Pediococcus parvulus 2.6 and in the recombinant strain Lactococcus lactis NZ9000[pNGTF] were tested. Their immunomodulatory activity was investigated in an ex vivo model using human biopsies from patients affected by Crohn's disease (CD). Both polymers had an anti-inflammatory effect including, a reduction of Interleukine 8 both at the level of its gene expression and its secreted levels. The overall data indicate that the O2-substituted-(1-3)-ß-D-glucan have a potential role in ameliorating inflammation via the gut immune system cell modulation.

[Symbiosis in the human gastrointestinal tract]. / Simbiosis en el tracto gastrointestinal humano.

INTRODUCTION: The human body is a planet populated by myriads of microorganisms all over its surface and in cavities connected to the outside. Experimental and clinical research is showing that microbial colonizers are a functional and essential part of the human organism. The microbial ecosystem, which is housed in the gastrointestinal tract, provides a "metagenome": genes and additional functions to the genetic resources of the species, which are involved in multiple physiological processes (somatic development, nutrition, immunity, etc.). The human intestine houses lymphoid structures specialized in the induction and regulation of adaptive immunity, and the interaction of the intestinal microbiota with the immune system of the digestive mucosa plays a key role for the individual's homeostasis with the outside world. Some chronic non-communicable inflammatory diseases in developed society are associated with dysbiosis: loss of species richness in the gut microbiota and deviation from the ancestral microbial environment. Generating and maintaining diversity in the gut microbiota is a new clinical goal for health promotion and disease prevention.

INTRODUCCIÓN: El cuerpo humano es un planeta poblado por miríadas de microorganismos en toda su superficie y en las cavidades conectadas con el exterior. La investigación experimental y clínica está demostrando que los colonizadores microbianos constituyen parte funcional y no prescindible del organismo humano. El ecosistema microbiano que se aloja en el tracto gastrointestinal aporta un "metagenoma": genes y funciones adicionales a los recursos genéticos de la especie, que participan en múltiples procesos fisiológicos (desarrollo somático, nutrición, inmunidad, etc.). El intestino humano alberga estructuras linfoides especializadas en la inducción y regulación de la inmunidad adaptativa. Asimismo, la interacción de la microbiota intestinal con el sistema inmunitario de la mucosa digestiva juega un papel clave para la homeostasis del individuo con el mundo exterior. Algunas enfermedades inflamatorias crónicas no transmisibles de la sociedad desarrollada se asocian a disbiosis: pérdida de riqueza de especies en la microbiota intestinal y desviación del entorno microbiano ancestral. Generar y mantener diversidad en la microbiota intestinal es un nuevo objetivo clínico para la promoción de salud y prevención de enfermedades.

Alterations in Gut Microbiome in Cirrhosis as Assessed by Quantitative Metagenomics: Relationship With Acute-on-Chronic Liver Failure and Prognosis.

BACKGROUND AND AIMS: Cirrhosis is associated with changes in gut microbiome composition. Although acute-on-chronic liver failure (ACLF) is the most severe clinical stage of cirrhosis, there is lack of information about gut microbiome alterations in ACLF using quantitative metagenomics. We investigated the gut microbiome in patients with cirrhosis encompassing the whole spectrum of disease (compensated, acutely decompensated without ACLF, and ACLF). A group of healthy subjects was used as control subjects. METHODS: Stool samples were collected prospectively in 182 patients with cirrhosis. DNA library construction and sequencing were performed using the Ion Proton Sequencer (ThermoFisher Scientific, Waltham, MA). Microbial genes were grouped into clusters, denoted as metagenomic species. RESULTS: Cirrhosis was associated with a remarkable reduction in gene and metagenomic species richness compared with healthy subjects. This loss of richness correlated with disease stages and was particularly marked in patients with ACLF and persisted after adjustment for antibiotic therapy. ACLF was associated with a significant increase of Enterococcus and Peptostreptococcus sp and a reduction of some autochthonous bacteria. Gut microbiome alterations correlated with model for end-stage liver disease and Child-Pugh scores and organ failure and was associated with some complications, particularly hepatic encephalopathy and infections. Interestingly, gut microbiome predicted 3-month survival with good stable predictors. Functional analysis showed that patients with cirrhosis had enriched pathways related to ethanol production, γ-aminobutyric acid metabolism, and endotoxin biosynthesis, among others. CONCLUSIONS: Cirrhosis is characterized by marked alterations in gut microbiome that parallel disease stages with maximal changes in ACLF. Altered gut microbiome was associated with complications of cirrhosis and survival. Gut microbiome may contribute to disease progression and poor prognosis. These results should be confirmed in future studies.

Antibiotics as Major Disruptors of Gut Microbiota.

Advances in culture-independent research techniques have led to an increased understanding of the gut microbiota and the role it plays in health and disease. The intestine is populated by a complex microbial community that is organized around a network of metabolic interdependencies. It is now understood that the gut microbiota is vital for normal development and functioning of the human body, especially for the priming and maturation of the adaptive immune system. Antibiotic use can have several negative effects on the gut microbiota, including reduced species diversity, altered metabolic activity, and the selection of antibiotic-resistant organisms, which in turn can lead to antibiotic-associated diarrhea and recurrent Clostridioides difficile infections. There is also evidence that early childhood exposure to antibiotics can lead to several gastrointestinal, immunologic, and neurocognitive conditions. The increase in the use of antibiotics in recent years suggests that these problems are likely to become more acute or more prevalent in the future. Continued research into the structure and function of the gut microbiota is required to address this challenge.