Alterations In Intestinal Microbiome Research Articles

Astragaloside IV Mitigated Diabetic Nephropathy by Restructuring Intestinal Microflora and Ferroptosis.

To investigate the underlying mechanism of Astragaloside IV (AS-IV) in ameliorating diabetic nephropathy (DN) by regulating intestinal microbiota ecology and intestinal mucosal barrier. Genetically db/db mice are used to establish DN mouse model to monitor the therapeutic effects of AS-IV and fecal microbiota transplantation (FMT) against DN. Supplementation with AS-IV dramatically attenuates several clinical indicators of DN in db/db mice. In addition, AS-IV markedly improves intestinal barrier function, modifies intestinal permeability, and reduces inflammation. Moreover, AS-IV treatment remarkably improves intestinal dysbiosis in db/db mice, characterized by an elevated abundance of Akkermansia, Ligilactobacillus, and Lactobacillus, indicating the fundamental role of the microbiome in DN progression. Furthermore, FMT derived from AS-IV-treated db/db mice is potentially efficient in antagonizing renal dysfunction, rebalancing gut microbiota, and improving intestinal permeability in recipient db/db mice. AS-IV-enriched Akkermansia muciniphila dramatically alleviates DN and intestinal mucosal barrier dysfunction in db/db mice. Intriguingly, AS-IV intervention dramatically diminishes ferroptosis in the kidney and colon tissues. CONCLUSION: Intestinal microbiome alterations and ferroptosis modulation by AS-IV may play instrumental roles in this mechanism, providing compelling evidence for the role of the gut-renal axis in DN.

S-amlodipine induces liver inflammation and dysfunction through the alteration of intestinal microbiome in a rat model.

S-amlodipine, a commonly prescribed antihypertensive agent, is widely used in clinical settings to treat hypertension. However, the potential adverse effects of long-term S-amlodipine treatment on the liver remain uncertain, given the cautionary recommendations from clinicians regarding its administration in individuals with impaired liver function. To address this, we conducted a study using an eight-week-old male rat model and administered a daily dose of 0.6 ~ 5 mg/kg of S-amlodipine for 7 weeks. Our findings demonstrated that 1.2 ~ 5 mg/kg of S-amlodipine treatment induced liver inflammation and associated dysfunction in rats, further in vitro experiments revealed that the observed liver inflammation and dysfunction were not attributable to direct effects of S-amlodipine on the liver. Metagenome sequencing analysis revealed that S-amlodipine treatment led to alterations in the gut microbiome of rats, with the bloom of E. coli (4.5 ~ 6.6-fold increase) and a decrease in A. muciniphila (1,613.4 ~ 2,000-fold decrease) and B. uniformis (20.6 ~ 202.7-fold decrease), subsequently causing an increase in the gut bacterial lipopolysaccharide (LPS) content (1.4 ~ 1.5-fold increase in feces). S-amlodipine treatment also induced damage to the intestinal barrier and increased intestinal permeability, as confirmed by elevated levels of fecal albumin; furthermore, the flux of gut bacterial LPS into the bloodstream through the portal vein resulted in an increase in serum LPS content (3.3 ~ 4-fold increase). LPS induces liver inflammation and subsequent dysfunction in rats by activating the TLR4 pathway. This study is the first to show that S-amlodipine induces liver inflammation and dysfunction by perturbing the rat gut microbiome. These results indicate the adverse effects of S-amlodipine on the liver and provide a rich understanding of the safety of long-term S-amlodipine administration.

The Role of Intestinal Microbiota in Celiac Disease and Further Therapeutic Perspectives.

Celiac disease (CD) is an immune-mediated enteropathy caused by exposure to gluten and related prolamins in genetically susceptible individuals. It is a complex genetic disorder with multiple contributing genes. Linkage studies have identified several genomic regions that probably contain CD susceptibility genes. The most important genetic factors are HLA-DQ2 and DQ8. Several known environmental triggers promote the onset of CD at any age after gluten introduction in individuals with a genetic background, such as viral infections and intestinal dysbiosis. Recent publications have described the interference of the intestinal microbiome in gluten metabolism, modulation of local immune reactions, and in maintaining normal gut permeability. These results have promoted further lines of research on the benefit of probiotic administration to prevent disease onset or alleviate clinical symptoms along with a gluten-free diet (GFD). The relationship between gut microbiome changes and the onset of CD is incompletely understood, still being the subject of current research. This narrative review analyzes the interplay between environmental factors, intestinal microbiome alterations, and the course of CD. Furthermore, this review sets out to discuss if modulation of intestinal microflora with pre- and probiotics along with a GFD could represent a reliable therapeutic target for celiac patients.

From Dysbiosis to Neurodegenerative Diseases through Different Communication Pathways: An Overview

The microbiome research field has rapidly evolved over the last few decades, becoming a major topic of scientific and public interest. The gut microbiota (GM) is the microbial population living in the gut. The GM has many functions, such as maintaining gut homeostasis and host health, providing defense against enteric pathogens, and involvement in immune system development. Several studies have shown that GM is implicated in dysbiosis and is presumed to contribute to neurodegeneration. This review focuses mainly on describing the connection between the intestinal microbiome alterations (dysbiosis) and the onset of neurodegenerative diseases to explore the mechanisms that link the GM to nervous system health, such as the gut-brain axis, as well as the mitochondrial, the adaptive humoral immunity, and the microvesicular pathways. The gut-brain communication depends on a continuous bidirectional flow of molecular signals exchanged through the neural and the systemic circulation. These pathways represent a possible new therapeutic target against neuroinflammation and neurodegeneration. Progress in this context is desperately needed, considering the severity of most neurodegenerative diseases and the current lack of effective treatments.

Gut microbiota is associated with response to 131I therapy in patients with papillary thyroid carcinoma

PurposeRadioactive iodine (131I) therapy is a conventional post-surgery treatment widely used for papillary thyroid carcinoma (PTC). Since 131I is orally administered, we hypothesize that it may affect gut microbiome. This study aims to investigate alterations of intestinal microbiome caused by 131I therapy in PTC patients and explore its association with response to 131I therapy.MethodsFecal samples of 60 PTC patients pre- and post-131I therapy were collected to characterize the 131I therapy-induced gut microbiota alterations using 16S rRNA gene sequencing. According to the inclusion criteria, sequence data of 40 out of the 60 patients, divided into excellent response (ER) group and non-excellent response (NER) group, were recruited to investigate the possible connection between gut microbiota and response to 131I therapy. Multivariate binary logistic regression was employed to construct a predictive model for response to 131I therapy.ResultsMicrobial richness, diversity, and composition were tremendously altered by 131I therapy. A significant decline of Firmicutes to Bacteroides (F/B) ratio was observed post-131I therapy. 131I therapy also led to changes of gut microbiome-related metabolic pathways. Discrepancies in β diversity were found between ER and NER groups both pre- and post-131I therapy. Furthermore, a predictive model for response to 131I therapy with a p value of 0.003 and an overall percentage correct of 80.0% was established, with three variables including lymph node metastasis, relative abundance of g_Bifidobacterium and g_Dorea. Among them, g_Dorea was identified to be an in independent predictor of response to 131I therapy (p = 0.04).ConclusionFor the first time, the present study demonstrates the gut microbial dysbiosis caused by 131I therapy in post-surgery PTC patients and reveals a previously undefined role of gut microbiome as predictor for 131I ablation response. G_Dorea and g_Bifidobacterium may be potential targets for clinical intervention to improve response to 131I in post-operative PTC patients.Trial registrationChiCTR2100048000. Registered 28 June 2021.

Colorectal microbiota after removal of colorectal cancer.

The colonic microbiome has been implicated in the pathogenesis of colorectal cancer (CRC) and intestinal microbiome alterations are not confined to the tumour. Since data on whether the microbiome normalises or remains altered after resection of CRC are conflicting, we studied the colonic microbiota of patients after resection of CRC. We profiled the microbiota using 16S rRNA gene amplicon sequencing in colonic biopsies from patients after resection of CRC (n = 63) in comparison with controls (n = 52), subjects with newly diagnosed CRC (n = 93) and polyps (i = 28). The colonic microbiota after surgical resection remained significantly different from that of controls in 65% of patients. Genus-level profiling and beta-diversity confirmed two distinct groups of patients after resection of CRC: one with an abnormal microbiota similar to that of patients with newly diagnosed CRC and another similar to non-CRC controls. Consumption levels of several dietary ingredients and cardiovascular drugs co-varied with differences in microbiota composition suggesting lifestyle factors may modulate differential microbiome trajectories after surgical resection. This study supports investigation of the colonic microbiota as a marker of risk for development of CRC.

Autonomic Nervous System Neuroanatomical Alterations Could Provoke and Maintain Gastrointestinal Dysbiosis in Autism Spectrum Disorder (ASD): A Novel Microbiome-Host Interaction Mechanistic Hypothesis.

Dysbiosis secondary to environmental factors, including dietary patterns, antibiotics use, pollution exposure, and other lifestyle factors, has been associated to many non-infective chronic inflammatory diseases. Autism spectrum disorder (ASD) is related to maternal inflammation, although there is no conclusive evidence that affected individuals suffer from systemic low-grade inflammation as in many psychological and psychiatric diseases. However, neuro-inflammation and neuro–immune abnormalities are observed within ASD-affected individuals. Rebalancing human gut microbiota to treat disease has been widely investigated with inconclusive and contradictory findings. These observations strongly suggest that the forms of dysbiosis encountered in ASD-affected individuals could also originate from autonomic nervous system (ANS) functioning abnormalities, a common neuro–anatomical alteration underlying ASD. According to this hypothesis, overactivation of the sympathetic branch of the ANS, due to the fact of an ASD-specific parasympathetic activity deficit, induces deregulation of the gut–brain axis, attenuating intestinal immune and osmotic homeostasis. This sets-up a dysbiotic state, that gives rise to immune and osmotic dysregulation, maintaining dysbiosis in a vicious cycle. Here, we explore the mechanisms whereby ANS imbalances could lead to alterations in intestinal microbiome–host interactions that may contribute to the severity of ASD by maintaining the brain–gut axis pathways in a dysregulated state.

Characterization and predictive functional profiles on metagenomic 16S rRNA data of liver transplant recipients: A longitudinal study.

Long-term survival after Liver Transplantation (LT) is often compromised by infectious and metabolic complications. We aimed to delineate alterations in intestinal microbiome (IM) over time that could contribute to medical complications compromising long-term survival following LT. Fecal samples from LT recipients were collected at 3 months (3M) and 6 months (6M) post-LT. The bacterial DNA was extracted using E.Z.N.A. Stool DNA Kit and 16S rRNA gene sequencing at V4 hypervariable region was performed. DADA2 and Phyloseq was implemented to analyze the taxonomic composition. Differentially abundant taxa were identified by metagenomeSeq and LEfSe. Piphillin, an Inferred functional metagenomic analysis tool was used to study the bacterial functional content. For comparison, healthy samples were extracted from NCBI and analyzed similarly. The taxonomic & functional profiles of LT recipients were validated with metagenomic sequencing data from animals exposed to immunosuppressants using Venny. Our findings provide a new perspective on longitudinal increase in specific IM communities post-LT along with an increase in bacterial genes associated with metabolic and infectious disease.

Impact of non-antibiotic drugs on the human intestinal microbiome

Introduction The gut microbiota is composed of trillions of microbial cells and viruses that interact with hosts. The composition of the gut microbiota is influenced by several factors including age, diet, diseases or medications. The impact of drugs on the microbiota is not limited to antibiotics and many non-antibiotic molecules significantly alter the composition of the intestinal microbiota. Areas covered This review focuses on the impact of four of the most widely prescribed non-antibiotic drugs in the world: Proton-pump inhibitors, metformin, statins and non-steroidal anti-inflammatory. We conducted a systematic review by searching online databases including Medline, Web of science and Scopus for indexed articles published in English until February 2021. We included studies assessing the intestinal microbiome alterations associated with proton pump inhibitors (PPIs), metformin, statins and nonsteroidal anti-inflammatory drugs (NSAIDs). Only studies using culture-independent molecular techniques were included. Expert opinion The taxonomical signature associated with non-antibiotic drugs are not yet fully described, especially in the field of metabolomic. The identification of taxonomic profiles associated a specific molecule provides information on its mechanism of action through interaction with the intestinal microbiota. Many side effects could be related to the dysbiosis induced by these molecules.

Developmental intestinal microbiome alterations in canine fading puppy syndrome: a prospective observational study

Fading puppy syndrome (FPS) is a fatal condition in neonatal dogs. Intestinal microbial alterations, although never investigated, may be involved in its pathophysiology. The study examined the occurrence of FPS and its associations with dam, puppy, and husbandry characteristics, compared the intestinal microbial diversity of healthy puppies and those with FPS, and examined whether intestinal microbiomes are predictive of FPS. Day 1 and 8 post-partum (PP) rectal swabs were collected from healthy puppies and puppies which later developed FPS. Microbial compositional structure, including alpha and beta diversities and relative abundance of specific taxa were compared between groups, and microbial data was applied to a machine-learning model to assess the predictive performance of microbial indices of FPS or death. FPS occurred in 22/165 puppies (13%), with a 100% mortality rate. FPS was associated (P < 0.001) with decreased Day 1 PP puppy activity. Day 1 (P = 0.003) and 8 (P = 0.005) PP rectal beta diversities were different in puppies with FPS vs healthy ones. Increased Proteobacteria/Firmicutes ratio, increased relative abundance of Pasteurellaceae, and decreased relative abundance of Clostridia and Enterococcus were associated with FPS. A machine-learning model showed that Day 1 PP rectal microbiome composition accurately predicted FPS-related death. We found that specific rectal microbial phenotypes are associated with FPS, reflecting the significant role of microbiome alterations in this phenomenon. These findings may serve as useful microbial indices for early diagnosis of puppies at risk of FPS and may provide specific therapeutic targets.

Alteration of Intestinal Microbiome of Clostridioides difficile-Infected Hamsters during the Treatment with Specific Cow Antibodies.

Clostridioides difficile infection (CDI) often develops after pretreatment with antibiotics, which can lead to damage of the intestinal microbiome. The approach of this study was to use specific polyclonal antibodies isolated from the milk of immunized cows to treat CDI, in contrast to the standard application of nonspecific antibiotics. To gain a deeper understanding of the role of the microbiome in the treatment of CDI with bovine antibodies, stool and intestinal fluid samples of hamsters were collected in large quantities from various treatments (>400 samples). The results show that the regeneration of the microbiome instantly begins with the start of the antibody treatment, in contrast to the Vancomycin-treated group where the diversity decreased significantly during the treatment duration. All antibody-treated hamsters that survived the initial phase also survived the entire study period. The results also show that the regeneration of the microbiome was not an antibody-induced regeneration, but a natural regeneration that occurred because no microbiota-inactivating substances were administered. In conclusion, the treatment with bovine antibodies is a functional therapy for both the acute treatment and the prevention of recurrence in hamsters and could meet the urgent need for CDI treatment alternatives in humans.

Sodium Butyrate Ameliorates Gut Microbiota Dysbiosis in Lupus-Like Mice.

Gut microbiota has a strong influence on the onset and development of systemic lupus erythematosus (SLE), and several studies have demonstrated the effectiveness of microbiota-derived butyrate to ameliorate SLE. However, the roles of butyrate on gut microbiota in SLE are not understood. Using MRL/lpr lupus-prone mice, we examined gut microbiota profiles after butyrate treatment by 16S rRNA sequencing. Alterations in intestinal microbiome in mice with lupus-like disease were mainly characterized by a reduction in microbial diversity, with an increased abundance of Bacteroidetes and a decrease of Firmicutes. Treatment of lupus-prone mice with butyrate resulted in increased abundance of Firmicutes (P = 0.003), Clostridia (P = 0.005), Clostridiales (P = 0.005), Lachnospiraceae (P = 0.009), Ruminococcaceae (P = 0.021), Peptostreptococcaceae (P = 0.021), Ruminiclostridium (P = 0.016), Oscillibacter (P = 0.048), Romboutsia (P = 0.025), Lachnoclostridium (P = 0.012), Coprococcus (P = 0.015), Ruminococcus (P = 0.011), Clostridium leptum (P < 0.05), and Dorea_spp. (P = 0.019), and a reduced proportion of Bacteroidetes (P = 0.004), Bacteroidia (P = 0.004), and Bacteroidales (P = 0.004). Further, butyrate supplementation could ameliorate kidney damage. Overall, this study suggests that gut microbiota alterations occur in MRL/lpr lupus-prone mice following treatment with butyrate. Butyrate supplementation ameliorated gut microbiota dysbiosis. These findings support the use of butyrate and butyrate-producing bacteria as potential treatments for SLE.

The Impact of Air Pollution on Intestinal Microbiome of Asthmatic Children: A Panel Study.

Air pollution could impact on the alteration of intestinal microbiome. Maturation of intestinal microbiome in early life played an important role in the development of allergic diseases, including asthma. Recent studies presented an increase in the evidence of association between the shift of gut microbiota and asthma. This article is aimed at exploring whether the alteration in the intestinal microbiome triggered by a short wave of air pollution could influence the colonization of bacteria that have been related to the immunological mechanisms of the asthma attack. The impact of air pollution on intestinal microbiome was assessed by longitudinal comparison. Fecal samples were collected twice for twenty-one children in clean and smog days, respectively, including eleven asthmatic children and ten healthy children. Intestinal bacteria were discriminated by using the method of 16S rRNA gene sequence. The results showed that the composition of intestinal microbiome changed between clean and smog days among all children (PERMANOVA, P = 0.03). During smog days, Bifidobacteriaceae, Erysipelotrichaceae, and Clostridium sensu stricto 1 decreased, and Streptococcaceae, Porphyromonadaceae, Rikenellaceae, Bacteroidales S24-7 group, and Bacteroides increased in asthmatic children (Wilcoxon test, P < 0.05), while Fusicatenibacter decreased and Rikenellaceae and Terrisporobacter increased in healthy children (Wilcoxon test, P < 0.05). After controlling for food consumption, the relative abundance of some bacteria belonging to Firmicutes negatively associated with concentration of PM2.5, PM10, NO2, and SO2 (multiple linear regression, P < 0.05). This study demonstrated that short wave of air pollution had an impact on the intestinal microbiome of asthmatic children. Intestinal bacteria, which have been related to immunological mechanisms of asthma attack, were also found to be associated with air pollution. This finding suggested that a short wave of air pollution may trigger asthma by impacting on intestinal bacteria.

Psoriasis Is Associated With Elevated Gut IL-1α and Intestinal Microbiome Alterations.

BackgroundPsoriasis is a chronic inflammatory condition that predominantly affects the skin and is associated with extracutaneous disorders, such as inflammatory bowel disease and arthritis. Changes in gut immunology and microbiota are important drivers of proinflammatory disorders and could play a role in the pathogenesis of psoriasis. Therefore, we explored whether psoriasis in a Central Asian cohort is associated with alterations in select immunological markers and/or microbiota of the gut.MethodsWe undertook a case-control study of stool samples collected from outpatients, aged 30–45 years, of a dermatology clinic in Kazakhstan presenting with plaque, guttate, or palmoplantar psoriasis (n = 20), and age-sex matched subjects without psoriasis (n = 20). Stool supernatant was subjected to multiplex ELISA to assess the concentration of 47 cytokines and immunoglobulins and to 16S rRNA gene sequencing to characterize microbial diversity in both psoriasis participants and controls.ResultsThe psoriasis group tended to have higher concentrations of most analytes in stool (29/47 = 61.7%) and gut IL-1α was significantly elevated (4.19-fold, p = 0.007) compared to controls. Levels of gut IL-1α in the psoriasis participants remained significantly unaltered up to 3 months after the first sampling (p = 0.430). Psoriasis was associated with alterations in gut Firmicutes, including elevated Faecalibacterium and decreased Oscillibacter and Roseburia abundance, but no association was observed between gut microbial diversity or Firmicutes/Bacteroidetes ratios and disease status.ConclusionsPsoriasis may be associated with gut inflammation and dysbiosis. Studies are warranted to explore the use of gut microbiome-focused therapies in the management of psoriasis in this under-studied population.

High-fat diet induces depression-like behaviour in mice associated with changes in microbiome, neuropeptide Y, and brain metabolome

Objectives: The biological mechanisms linking diet-related obesity and depression remain unclear. Therefore, we examined the impact of high-fat diet (HFD) on murine behaviour, intestinal microbiome, brain metabolome, neuropeptide Y (NPY) expression, and dipeptidyl peptidase-4 (DPP-4) activity.Methods: Male C57Bl/6J mice were fed an HFD (60 kJ% from fat) or control diet (12 kJ% from fat) for 8 weeks, followed by behavioural phenotyping. Caecal microbiome was analysed by 16S rDNA sequencing, brain metabolome by 1H nuclear magnetic resonance, NPY expression by PCR and immunoassay, and dipeptidyl peptidase-4 (DPP-4) activity by enzymatic assay. The effect of a 4-week treatment with imipramine (7 mg/kg/day) and the DPP-4 inhibitor sitagliptin (50 mg/kg/day) on HFD-induced behavioural changes was also tested.Results: HFD led to a depression-like phenotype as revealed by reduced sociability and sucrose preference. In the caecum, HFD diminished the relative abundance of Bacteroidetes and increased the relative abundance of Firmicutes and Cyanobacteria. In the brain, HFD modified the metabolome of prefrontal cortex and striatum, changing the relative concentrations of molecules involved in energy metabolism (e.g. lactate) and neuronal signalling (e.g. γ-aminobutyric acid). The expression of NPY in hypothalamus and hippocampus was decreased by HFD, whereas plasma NPY and DPP-4-like activity were increased. The HFD-induced anhedonia remained unaltered by imipramine and sitagliptin.Discussion: The depression-like behaviour induced by prolonged HFD in mice is associated with distinct alterations of intestinal microbiome, brain metabolome, NPY system, and DPP-4-like activity. Importantly, the HFD-evoked behavioural disturbance remains unaltered by DPP-4 inhibition and antidepressant treatment with imipramine.

Smoking and the intestinal microbiome.

Studies are emerging alluding to the role of intestinal microbiome in the pathogenesis of diseases. Intestinal microbiome is susceptible to the influence of environmental factors such as smoking, and recent studies have indicated microbiome alterations in smokers. The aim of the study was to review the literature regarding the impact of smoking on the intestinal microbiome. A literature review of publications in PUBMED was performed using combinations of the terms "Intestinal/Gut/Gastrointestinal/Colonic" with "Microbiome/Microbiota/Microbial/Flora" and "Smoking/Smoker/Tobacco". We selected studies that were published between the years 2000 and 2016 as our inclusion criteria. Observational and interventional studies suggest that the composition of intestinal microbiome is altered due to smoking. In these studies, Proteobacteria and Bacteroidetes phyla were increased, as well as the genera of Clostridium, Bacteroides and Prevotella. On the other hand, Actinobacteria and Firmicutes phyla as well as the genera Bifidobacteria and Lactococcus were decreased. Smoking also decreased the diversity of the intestinal microbiome. Mechanisms that have been suggested to explain the effect of smoking on intestinal microbiome include: oxidative stress enhancement, alterations of intestinal tight junctions and intestinal mucin composition, and changes in acid-base balance. Interestingly, some smoking-induced alterations of intestinal microbiome resemble those demonstrated in conditions such as inflammatory bowel disease and obesity. Further studies should be performed to investigate this connection. Smoking has an effect on intestinal microbiome and is suggested to alter its composition. This interaction may contribute to the development of intestinal and systemic diseases, particularly inflammatory bowel diseases.

The Artificial Sweetener Splenda Promotes Gut Proteobacteria, Dysbiosis, and Myeloperoxidase Reactivity in Crohn's Disease-Like Ileitis.

BackgroundEpidemiological studies indicate that the use of artificial sweeteners doubles the risk for Crohn’s disease (CD). Herein, we experimentally quantified the impact of 6-week supplementation with a commercial sweetener (Splenda; ingredients sucralose maltodextrin, 1:99, w/w) on both the severity of CD-like ileitis and the intestinal microbiome alterations using SAMP1/YitFc (SAMP) mice.MethodsMetagenomic shotgun DNA sequencing was first used to characterize the microbiome of ileitis-prone SAMP mice. Then, 16S rRNA microbiome sequencing, quantitative polymerase chain reaction, fluorescent in situ hybridization (FISH), bacterial culture, stereomicroscopy, histology, and myeloperoxidase (MPO) activity analyses were then implemented to compare the microbiome and ileitis phenotype in SAMP with that of control ileitis-free AKR/J mice after Splenda supplementation.ResultsMetagenomics indicated that SAMP mice have a gut microbial phenotype rich in Bacteroidetes, and experiments showed that Helicobacteraceae did not have an exacerbating effect on ileitis. Splenda did not increase the severity of (stereomicroscopic/histological) ileitis; however, biochemically, ileal MPO activity was increased in SAMP treated with Splenda compared with nonsupplemented mice (P < 0.022) and healthy AKR mice. Splenda promoted dysbiosis with expansion of Proteobacteria in all mice, and E. coli overgrowth with increased bacterial infiltration into the ileal lamina propria of SAMP mice. FISH showed increase malX gene–carrying bacterial clusters in the ilea of supplemented SAMP (but not AKR) mice.ConclusionsSplenda promoted gut Proteobacteria, dysbiosis, and biochemical MPO reactivity in a spontaneous model of (Bacteroidetes-rich) ileal CD. Our results indicate that although Splenda may promote parallel microbiome alterations in CD-prone and healthy hosts, this did not result in elevated MPO levels in healthy mice, only CD-prone mice. The consumption of sucralose/maltodextrin-containing foods might exacerbate MPO intestinal reactivity only in individuals with a pro-inflammatory predisposition, such as CD.

Systematic review: human gut dysbiosis induced by non-antibiotic prescription medications.

Global prescription drug use has been increasing continuously for decades. The gut microbiome, a key contributor to health status, can be altered by prescription drug use, as antibiotics have been repeatedly described to have both short-term and long-standing effects on the intestinal microbiome. To summarise current findings on non-antibiotic prescription-induced gut microbiome changes, focusing on the most frequently prescribed therapeutic drug categories. We conducted a systematic review by first searching in online databases for indexed articles and abstracts in accordance with PRISMA guidelines. Studies assessing the intestinal microbiome alterations associated with proton pump inhibitors (PPIs), metformin, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, statins and antipsychotics were included. We only included studies using culture-independent molecular techniques. Proton pump inhibitors and antipsychotic medications are associated with a decrease in α diversity in the gut microbiome, whereas opioids were associated with an increase in α diversity. Metformin and NSAIDs were not associated with significant changes in α diversity. β diversity was found to be significantly altered with all drugs, except for NSAIDs. PPI use was linked to a decrease in Clotridiales and increase in Actinomycetales, Micrococcaceae and Streptococcaceae, which are changes previously implicated in dysbiosis and increased susceptibility to Clostridium difficile infection. Consistent results showed that PPIs, metformin, NSAIDs, opioids and antipsychotics were either associated with increases in members of class Gammaproteobacteria (including Enterobacter, Escherichia, Klebsiella and Citrobacter), or members of family Enterococcaceae, which are often pathogens isolated from bloodstream infections in critically ill patients. We also found that antipsychotic treatment, usually associated with an increase in body mass index, was marked by a decreased ratio of Bacteroidetes:Firmicutes in the gut microbiome, resembling trends seen in obese patients. Non-antibiotic prescription drugs have a notable impact on the overall architecture of the intestinal microbiome. Further explorations should seek to define biomarkers of dysbiosis induced by specific drugs, and potentially tailor live biotherapeutics to counter this drug-induced dysbiosis. Many other frequently prescribed drugs should also be investigated to better understand the link between these drugs, the microbiome and health status.

Alterations of Intestinal Microbiome by Antibiotic Therapy in Hospitalized Children.

The administration of antimicrobial agents leads to an ecological imbalance of the host-microorganisms relationship, and it causes a rapid and significant reduction in the microbial diversity. The aim of the current study was to evaluate the impact of antibiotic therapy on intestinal microbiota of children between 3 and 12 years of age. The fecal samples were collected from hospitalized children (n = 31) and from healthy untreated children (n = 30). The presence of bacteria and their quantities were assessed by culture-based methods and quantitative polymerase chain reaction (qPCR). By culture method, in the children receiving antibiotics, a low recovery of Bifidobacterium spp. (54.8%), Bacteroides spp./Parabacteroides spp. (54.8%), Clostridium spp. (35.5%), and Escherichia coli (74.2%) was observed compared with the children without antibiotic therapy (100%, 80%, 63.3%, and 86.6%, respectively). By qPCR, the children receiving antibiotics showed a lower copy number for all microorganisms, except to Lactobacillus spp. (p = 0.0092). In comparison to the nontreated children, the antibiotic-treated children showed a significantly lower copy number of Bifidobacterium spp. (p = 0.0002), Clostridium perfringens (p < 0.0001), E. coli (p = 0.0268), Methanobrevibacter smithii (p = 0.0444), and phylum Firmicutes (p = 0.0009). In conclusion, our results obtained through qualitative and quantitative analyses, demonstrate that antibiotic therapy affect the intestinal microbiome of children.

Probiotics: current evidences and new perspectives

Probiotics are viable microorganisms that can exert potential benefits to human health. Use of probiotics in different human diseases and clinical conditions has gained much attention in the last decades. Several data exist about the potential benefits of probiotics in pediatric age for the management of some clinical conditions, with different and sometimes contrasting results. Currently, strong evidences support the use of probiotics for treatment of acute infectious diarrhoea and prevention of antibiotic-associated diarrhoea: bacteria belonging to the genus of lactobacilli and Saccharomyces boulardii showed the stronger evidences of benefits in different clinical trials and meta-analysis [1,2]. For other pediatric diseases and clinical conditions, evidences of the benefits of a probiotic supplementation are still not so strong. The recommendation to administer a probiotics supplementation in preterm, very low birth weight neonates at risk of developing necrotizing enterocolitis has recently been criticized by a critical review of the literature that conclude that well-designed clinical trials are still needed for suggesting its routinely use in these neonates [3]. Discussion is still ongoing about the benefits of probiotics in prevention or treatment of other pediatric diseases such as respiratory tract infections, urinary tract infections, Helicobacter pylori infection or allergic diseases. Clinical trials and meta-analysis about the use of probiotics in these pediatric clinical conditions have been published and still continued to be published; however, study designs are not always comparable and sometimes inadequate, species of probiotics used in the studies are different and the benefits demonstrated for one microorganism are not generalizable to other bacteria, results of the studies are still often not unequivocal or contrasting so that strong recommendations are still lacking. The use of probiotics has been suggested to be potentially beneficial for the management of gastrointestinal functional disorders, such as irritable bowel syndrome, again, with different results. These clinical conditions are supposed to be the result of a perturbation of the microbiota balance that leads to dysbiosis, responsible for the appearance of the characteristic symptoms. However, pathogenesis of gastrointestinal functional disorders appear to be much more complex and involve the nervous system and its bidirectional interactions with the intestine. Moreover, it has been hypothesized that intestinal microbial composition may itself influence end-points related to mood state, brain function, and mental outlook. A new fascinating perspective in studies about microbiota and probiotics is the characterization of the alterations of intestinal microbiome and their correlation with abnormalities in the bidirectional gut-brain interactions.