Plasma bile acids in association with Crohn's disease.

BACKGROUND: In addition to facilitating lipid digestions, bile acids (BA) are signalling molecules acting on receptors on immune cells and along the gastrointestinal (GI) tract. The aim of this study was to assess if altered bile acid profiles in plasma are associated with Crohn's disease (CD). METHOD: This cross-sectional study included individuals (aged ≥18 years) referred for colonoscopy at a tertiary centre in Stockholm between 2016 and 2019. All participants received bowel preparation, completed a lifestyle questionnaire and provided blood samples for analysis. During colonoscopy, severity of disease was graded, and biopsies were taken from colonic mucosa. In the current substudy, 88 individuals with CD and 88 age-matched controls were selected for analysis of BA in plasma with ultra performance liquid chromatography (UPLC). Linear regression models were then used to compare mean bile acid concentrations and concentration ratios between CD and controls. RESULTS: Individuals with CD had lower plasma concentrations of the majority of secondary BA compared to controls, in total CD/CC ratio 0.60 (SE 0.12), p = 0.001. The most prominent observations were lower levels of deoxycolic acid derivates and lithocolic acid derivates among participants with CD. Moreover, plasma concentration for secondary BA among participants with active CD was significantly lower compared to those with CD in remission, CD active/CD remission ratio 0.65 (SE 0.11), p < 0.002. CONCLUSION: Crohn's disease may be associated with altered plasma bile acid composition. The significance of colonic bacterial diversity in this context needs to be investigated in further studies.

It is known that Crohn's disease is associated with dysbiosis in the gut microbiota and that primary bile acids are transformed to secondary bile acids by bacterial enzymes in the gut before reabsorbed and transported back to the liver.In this cross-sectional study, Crohn's disease was associated with lower concentrations of secondary bile acids in blood plasmaThe findings should encourage further studies the role of the gut microbiome and bile acid metabolism in development of Crohn's disease and bile acid profile as a biomarker for bowel inflammation.

Clostridioides difficile recurrence in individuals with and without cancer: a Swedish population-based cohort study.

PURPOSE: Patients with cancer are vulnerable to Clostridioides difficile infection (CDI) due to their disease, treatment and regular hospital contact, yet if CDI-recurrence is more common remains unclear, and differences among cancer types remain unexplored. METHODS: This Swedish nationwide population-based cohort included all 43,150 individuals with recorded CDI (2006-2019) to assess CDI-recurrence in individuals with and without cancer, with binary multivariable logistic regression, stratified by anatomical location, and survival status. RESULTS: Compared to those without cancer (N = 29,543), ongoing cancer (diagnosis < 12 months; N = 3,882) was associated with reduced recurrence (OR = 0.81, 95% CI 0.73-0.89), while there was no association with cancer history (diagnosis ≥ 12 months; N = 9,725). There was an increased 8-week all-cause mortality (Ongoing cancer: OR = 1.58, 95% CI 1.43-1.74; Cancer history: OR = 1.45, 95% CI 1.36-1.55) compared to those without cancer. Among CDI-survivors, those with ongoing cancer presented with a decreased odds of recurrence (OR = 0.84, 95% CI 0.76-0.94), compared to those without cancer history, with no association for those with cancer history (OR = 1.04, 95% CI 0.97-1.1). Large variations were seen across cancer types, with the highest observed proportion of recurrence in oral and mesothelial cancer, and the lowest for esophageal cancer, although no statistically significant OR were found. CONCLUSION: The population-based study indicates that individuals with cancer may have fewerrecurrences than expected, yet variations by cancer type were large, and mortality was high.

The combined effect of systemic antibiotics and proton pump inhibitors on Clostridioides difficile infection and recurrence.

BACKGROUND: Antibiotics and proton pump inhibitors (PPI) are recognized risk factors for acquisition and recurrence of Clostridioides difficile infection (CDI), yet combined effects remain unclear. OBJECTIVES: To assess the short- and long-term effects of antibiotics and PPIs on CDI risk and recurrence. METHODS: Population-based study including all 43 152 patients diagnosed with CDI in Sweden (2006-2019), and 355 172 matched population controls without CDI. The impact of antibiotics and PPIs on CDI risk and recurrence was explored for recent (0-30 days) and preceding (31-180 days) use prior to their first CDI diagnosis, using multivariable conditional logistic regression presented as odds ratios (ORs) and 95% confidence interval, adjusted for demographics, comorbidities and other drugs. RESULTS: Compared to controls, the combined effect of recent PPIs and antibiotics [ORAB+PPI = 17.51 (17.48-17.53)] on CDI risk was stronger than the individual effects [ORAB = 15.37 (14.83-15.93); ORPPI = 2.65 (2.54-2.76)]. Results were less pronounced for exposure during the preceding months. Dose-response analyses showed increasing exposure correlated with CDI risk [recent use: ORAB = 6.32 (6.15-6.49); ORPPI = 1.65 (1.62-1.68) per prescription increase].Compared to individuals without recurrence (rCDI), recent [ORAB = 1.30 (1.23-1.38)] and preceding [ORAB = 1.23 (1.16-1.31); ORPPI = 1.12 (1.03-1.21)] use also affected the risk of recurrence yet without significant interaction between both. Recent macrolides/lincosamides/streptogramins; other antibacterials including nitroimidazole derivates; non-penicillin beta lactams and quinolones showed the strongest association with CDI risk and recurrence, particularly for recent use. PPI use, both recent and preceding, further increased the CDI risk associated with almost all antibiotic classes. CONCLUSION: Recent and less recent use of PPIs and systemic antibiotics was associated with an increased risk of CDI, particularly in combination.

Precision microbial intervention improves social behavior but not autism severity: A pilot double-blind randomized placebo-controlled trial.

Autism spectrum disorder (ASD) is characterized by the presence of restricted/repetitive behaviors and social communication deficits. Because effective treatments for ASD remain elusive, novel therapeutic strategies are necessary. Preclinical studies show that L. reuteri selectively reversed social deficits in several models for ASD. Here, in a double-blind, randomized, placebo-controlled trial, we tested the effect of L. reuteri (a product containing a combination of strains ATCC-PTA-6475 and DSM-17938) in children with ASD. The treatment does not alter overall autism severity, restricted/repetitive behaviors, the microbiome composition, or the immune profile. However, L. reuteri combination yields significant improvements in social functioning that generalized across different measures. Interestingly, ATCC-PTA-6475, but not the parental strain of DSM-17938, reverses the social deficits in a preclinical mouse model for ASD. Collectively, our findings show that L. reuteri enhances social behavior in children with ASD, thereby warranting larger trials in which strain-specific effects should also be investigated.

Alterations in the gut microbiome and its metabolites are associated with the immune response to mucosal immunization with Lactiplantibacillus plantarum-displaying recombinant SARS-CoV-2 spike epitopes in mice.

Lactic acid bacteria (LAB) expressing foreign antigens have great potential as mucosal vaccines. Our previous study reported that recombinant Lactiplantibacillus plantarum SK156 displaying SARS-CoV-2 spike S1 epitopes elicited humoral and cell-mediated immune responses in mice. Here, we further examined the effect of the LAB-based mucosal vaccine on gut microbiome composition and function, and gut microbiota-derived metabolites. Forty-nine (49) female BALB/c mice were orally administered L. plantarum SK156-displaying SARS-CoV-2 spike S1 epitopes thrice (at 14-day intervals). Mucosal immunization considerably altered the gut microbiome of mice by enriching the abundance of beneficial gut bacteria, such as Muribaculaceae, Mucispirillum, Ruminococcaceae, Alistipes, Roseburia, and Clostridia vadinBB60. Moreover, the predicted function of the gut microbiome showed increased metabolic pathways for amino acids, energy, carbohydrates, cofactors, and vitamins. The fecal concentration of short-chain fatty acids, especially butyrate, was also altered by mucosal immunization. Notably, alterations in gut microbiome composition, function, and butyrate levels were positively associated with the immune response to the vaccine. Our results suggest that the gut microbiome and its metabolites may have influenced the immunogenicity of the LAB-based SARS-CoV-2 vaccine.

Safety and tolerability of frozen, capsulized autologous faecal microbiota transplantation. A randomized double blinded phase I clinical trial.

BACKGROUND: Faecal microbiota transplantation (FMT) is recommended treatment for recurrent Clostridioides difficile infection and is studied as a potential modifier of other gastrointestinal and systemic disorders. Autologous FMT limits the potential risks of donor transplant material and enables prophylactic treatment. Capsulized FMT is convenient and accessible, but safety data are lacking. AIMS: To describe safety and tolerability of capsules containing autologous FMT, compared to placebo, in healthy volunteers treated with antibiotics. METHOD: Healthy volunteers without antibiotic exposure during the past three months, that had a negative Clostridioides difficile stool sample, were recruited. Study persons donated faeces for production of capsules containing autologous microbiota. They were then given Clindamycin for seven days to disrupt the intestinal microbiota, which was followed by a two-day washout. Study persons were then randomized (1:1) to unsupervised treatment with autologous faecal matter or placebo, with two capsules twice daily for five days. A standardized questionnaire about side effects and tolerability, daily until day 28, and on days 60 and 180, was completed. RESULTS: Twenty-four study persons were included, all completed the treatment. One person from the placebo and FMT groups each, were lost to follow up from days 21 and 60, respectively. No study person experienced serious side effects, but severe fatigue was reported during the antibiotic period (n = 2). Reported side effects were mild to moderate and there were no significant differences between the groups. Reported general and intestinal health improved significantly and similarly in both groups after the antibiotic treatment. Time to normalized intestinal habits were 17 and 19 days from study start in the placebo group and the FMT group, respectively (p = 0.8). CONCLUSION: Capsulized frozen autologous faecal microbiota transplantation was safe and well tolerated but did not affect time to normalized intestinal habits compared to placebo. TRIAL REGISTRATION: EudraCT 2017-002418-30.

Clostridioides difficile infection-associated cause-specific and all-cause mortality: a population-based cohort study.

OBJECTIVES: Clostridioides difficile infection (CDI) is a common healthcare-associated infection and leading cause of gastroenteritis-related mortality worldwide. However, data on CDI-associated mortality are scarce. We aimed to examine the association between CDI and all-cause and cause-specific mortality. We additionally explored contributing causes of mortality, including recurrent CDI, hospital- or community-acquired CDI, chronic comorbidities, and age. METHODS: This nationwide population-based cohort study (from 2006 to 2019) compared individuals with CDI with the entire Swedish background population using standardized mortality ratios. In addition, a matched-cohort design (1:10), utilizing multivariable Poisson-regression models, provided incidence rate ratios (IRRs) with 95% CIs. RESULTS: This study included 43 150 individuals with CDI and 355 172 controls. In total, 69.7% were ≥65 years, and 54.9% were female. CDI was associated with a 3- to 7-fold increased mortality rate (IRR = 3.5, 95% CI: 3.3-3.6; standardized mortality ratio = 6.8, 95% CI: 6.7-6.9) compared with the matched controls and Swedish background population, respectively. Mortality rates were highest for hospital-acquired CDI (IRR = 2.4, 95% CI: 1.9-3.2) and during the first CDI episode (IRR = 0.2, 95% CI: 0.2-0.3 for recurrent versus first CDI). Individuals with CDI had more chronic comorbidities than controls, yet mortality remained higher among CDI cases even after adjustment and stratification for comorbidity; CDI was associated with increased mortality (IRR = 6.1, 95% CI: 5.5-6.8), particularly among those without any chronic comorbidities. DISCUSSION: CDI was associated with elevated all-cause and cause-specific mortality, despite possible confounding by ill health. Mortality rates were consistently increased across sexes, all age groups, and comorbidity groups.

Helicobacter pylori attachment-blocking antibodies protect against duodenal ulcer disease.

The majority of the world population carry the gastric pathogen Helicobacter pylori. Fortunately, most individuals experience only low-grade or no symptoms, but in many cases the chronic inflammatory infection develops into severe gastric disease, including duodenal ulcer disease and gastric cancer. Here we report on a protective mechanism where H. pylori attachment and accompanying chronic mucosal inflammation can be reduced by antibodies that are present in a vast majority of H. pylori carriers. These antibodies block binding of the H. pylori attachment protein BabA by mimicking BabA's binding to the ABO blood group glycans in the gastric mucosa. However, many individuals demonstrate low titers of BabA blocking antibodies, which is associated with an increased risk for duodenal ulceration, suggesting a role for these antibodies in preventing gastric disease.

Evaluation of plasma Short chain fatty acid levels as markers for Inflammatory bowel disease.

BACKGROUND: Specific variations of short chain fatty acids in fecal samples have been shown for patients with inflammatory bowel disease. The aim of this study was to assess if Crohn's disease and ulcerative colitis are associated with altered concentrations of short chain fatty acids also in blood plasma. METHOD: Between 2016-2019, Swedish adults referred to a tertiary center for colonoscopy were asked to participate in a cross-sectional study. Individuals with Crohn's disease or ulcerative colitis as well as individuals with no findings on the colonoscopy (defined as clean colon) were included in the study. Data on colonoscopy findings, blood samples (including haemoglobin, C-reactive protein and short chain fatty acid analysis) as well as a validated lifestyle questionnaire including 277 questions were collected from all participants. Linear regression was used to compare mean concentrations of short chain fatty acids between Crohn's disease, ulcerative colitis and clean colon. RESULTS: The cohort consisted of 132 individuals with Crohn's disease, 119 with ulcerative colitis and 205 with clean colon. In the crude model, succinic acid was significantly lower (p < 0.05) among patients with Crohn's disease (mean 3.00 µM SE 0.10) and ulcerative colitis (mean 3.13 µM SE 0.10) in comparison to clean colon (mean 3.41 µM SE 0.08), however when adjusting for sex, age and diet the results did not remain statistically significant. No differences in plasma concentration of the other measured short chain fatty acids were detected. CONCLUSION: Crohn's disease and ulcerative colitis are not associated with altered short chain fatty acid concentrations in plasma. Further research is needed to confirm or refute our findings.

In this cross-sectional study including individuals with inflammatory bowel disease and healthy subjects we found no association between Crohn's disease and ulcerative colitis and short chain fatty acid concentrations in plasma.

Antibiotic use and development of nonalcoholic fatty liver disease: A population-based case-control study.

BACKGROUND AND AIMS: Antibiotics affect the gut microbiome. Preclinical studies suggest a role of gut dysbiosis in the development of nonalcoholic fatty liver disease (NAFLD), but data from large cohorts with liver histology are lacking. METHODS: In this nationwide case-control study, Swedish adults with histologically confirmed early-stage NAFLD (total n = 2584; simple steatosis n = 1435; steatohepatitis (NASH) n = 383; non-cirrhotic fibrosis n = 766) diagnosed January 2007-April 2017 were included and matched to ≤5 population controls (n = 12 646) for age, sex, calendar year and county of residence. Data for cumulative antibiotic dispensations and defined daily doses were accrued until 1 year before the matching date. Using conditional logistic regression, multivariable-adjusted odds ratios (aORs) were calculated. In a secondary analysis, NAFLD patients were compared with their full siblings (n = 2837). RESULTS: Previous antibiotic use was seen in 1748 (68%) NAFLD patients versus 7001 (55%) controls, corresponding to 1.35-fold increased odds of NAFLD (95% CI = 1.21-1.51) in a dose-dependent manner (pfor trend < .001). Estimates were comparable for all histologic stages (p > .05). The highest risk of NAFLD was observed after treatment with fluoroquinolones (aOR 1.38; 95% CI = 1.17-1.59). Associations remained robust when patients were compared with their full siblings (aOR 1.29; 95% CI = 1.08-1.55). Antibiotic treatment was only linked to NAFLD in patients without metabolic syndrome (aOR 1.63; 95% CI = 1.35-1.91) but not in those with metabolic syndrome (aOR 1.09; 95% CI = 0.88-1.30). CONCLUSIONS: Antibiotic use may be a risk factor for incident NAFLD, especially in individuals without the metabolic syndrome. The risk was highest for fluoroquinolones and remained robust in sibling comparisons with whom individuals share genetic and early environmental susceptibilities.

Mucosal immunization with lactiplantibacillus plantarum-displaying recombinant SARS-CoV-2 epitopes on the surface induces humoral and mucosal immune responses in mice.

BACKGROUND: The use of probiotic lactic acid bacteria as a mucosal vaccine vector is considered a promising alternative compared to the use of other microorganisms because of its "Generally Regarded as Safe" status, its potential adjuvant properties, and its tolerogenicity to the host. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease (COVID-19), is highly transmissible and pathogenic. This study aimed to determine the potential of Lactiplantibacillus plantarum expressing SARS-CoV-2 epitopes as a mucosal vaccine against SARS-CoV-2. RESULTS: In this study, the possible antigenic determinants of the spike (S1-1, S1-2, S1-3, and S1-4), membrane (ME1 and ME2), and envelope (E) proteins of SARS-CoV-2 were predicted, and recombinant L. plantarum strains surface-displaying these epitopes were constructed. Subsequently, the immune responses induced by these recombinant strains were compared in vitro and in vivo. Most surface-displayed epitopes induced pro-inflammatory cytokines [tumor necrosis factor alpha (TNF-α and interleukin (IL)-6] and anti-inflammatory cytokines (IL-10) in lipopolysaccharide-induced RAW 264.7, with the highest anti-inflammatory to pro-inflammatory cytokine ratio in the S1-1 and S1-2 groups, followed by that in the S1-3 group. When orally administered of recombinant L. plantarum expressing SARS-CoV-2 epitopes in mice, all epitopes most increased the expression of IL-4, along with induced levels of TNF-α, interferon-gamma, and IL-10, specifically in spike protein groups. Thus, the surface expression of epitopes from the spike S1 protein in L. plantarum showed potential immunoregulatory effects, suggesting its ability to potentially circumvent hyperinflammatory states relevant to monocyte/macrophage cell activation. At 35 days post immunization (dpi), serum IgG levels showed a marked increase in the S1-1, S1-2, and S1-3 groups. Fecal IgA levels increased significantly from 21 dpi in all the antigen groups, but the boosting effect after 35 dpi was explicitly observed in the S1-1, S1-2, and S1-3 groups. Thus, the oral administration of SARS-CoV-2 antigens into mice induced significant humoral and mucosal immune responses. CONCLUSION: This study suggests that L. plantarum is a potential vector that can effectively deliver SARS-CoV-2 epitopes to intestinal mucosal sites and could serve as a novel approach for SARS-CoV-2 mucosal vaccine development.

Atlas of mRNA translation and decay for bacteria.

Regulation of messenger RNA stability is pivotal for programmed gene expression in bacteria and is achieved by a myriad of molecular mechanisms. By bulk sequencing of 5' monophosphorylated mRNA decay intermediates (5'P), we show that cotranslational mRNA degradation is conserved among both Gram-positive and -negative bacteria. We demonstrate that, in species with 5'-3' exonucleases, the exoribonuclease RNase J tracks the trailing ribosome to produce an in vivo single-nucleotide toeprint of the 5' position of the ribosome. In other species lacking 5'-3' exonucleases, ribosome positioning alters endonucleolytic cleavage sites. Using our metadegradome (5'P degradome) sequencing approach, we characterize 5'P mRNA decay intermediates in 96 species including Bacillus subtilis, Escherichia coli, Synechocystis spp. and Prevotella copri and identify codon- and gene-level ribosome stalling responses to stress and drug treatment. We also apply 5'P sequencing to complex clinical and environmental microbiomes and demonstrate that metadegradome sequencing provides fast, species-specific posttranscriptional characterization of responses to drug or environmental perturbations. Finally we produce a degradome atlas for 96 species to enable analysis of mechanisms of RNA degradation in bacteria. Our work paves the way for the application of metadegradome sequencing to investigation of posttranscriptional regulation in unculturable species and complex microbial communities.

A 3D Bioprinted Gut Anaerobic Model for Studying Bacteria-Host Interactions.

The role of the human intestinal tract in host-microbe interactions has been highlighted in recent years. Several 3-dimensional (3D) models have been developed to reproduce the physiological characteristics of the human gut and to investigate the function of the gut microbiota. One challenge for 3D models is to recapitulate the low oxygen concentrations in the intestinal lumen. Moreover, most earlier 3D culture systems used a membrane to physically separate bacteria from the intestinal epithelium, which has sometimes made the studies of bacteria adhering to or invading cells less feasible. We report the establishment of a 3D gut epithelium model and cultured it at high cell viability under an anaerobic condition. We further cocultured intestinal bacteria including both commensal and pathogen directly with epithelial cells in the established 3D model under the anaerobic condition. We subsequently compared the gene expression differences of aerobic and anaerobic conditions for cell and bacterial growth via dual RNA sequencing. Our study provides a physiologically relevant 3D gut epithelium model that mimics the anaerobic condition in the intestinal lumen and supplies a powerful system for future in-depth gut-microbe interactional investigations.

The Local Tumor Microbiome Is Associated with Survival in Late-Stage Colorectal Cancer Patients.

The gut microbiome is associated with survival in colorectal cancer. Single organisms have been identified as markers of poor prognosis. However, in situ imaging of tumors demonstrate a polymicrobial tumor-associated community. To understand the role of these polymicrobial communities in survival, we conducted a nested case-control study in late-stage cancer patients undergoing resection for primary adenocarcinoma. The microbiome of paired tumor and adjacent normal tissue samples was profiled using 16S rRNA sequencing. We found a consistent difference in the microbiome between paired tumor and adjacent tissue, despite strong individual microbial identities. Furthermore, a larger difference between normal and tumor tissue was associated with prognosis: patients with shorter survival had a larger difference between normal and tumor tissue. Within the tumor tissue, we identified a 39-member community statistic associated with survival; for every log2-fold increase in this value, an individual's odds of survival increased by 20% (odds ratio survival 1.20; 95% confidence interval = 1.04 to 1.33). Our results suggest that a polymicrobial tumor-specific microbiome is associated with survival in late-stage colorectal cancer patients. IMPORTANCE Microbiome studies in colorectal cancer (CRC) have primarily focused on the role of single organisms in cancer progression. Recent work has identified specific organisms throughout the intestinal tract, which may affect survival; however, the results are inconsistent. We found differences between the tumor microbiome and the microbiome of the rest of the intestine in patients, and the magnitude of this difference was associated with survival, or, the more like a healthy gut a tumor looked, the better a patient's prognosis. Our results suggest that future microbiome-based interventions to affect survival in CRC will need to target the tumor community.

Identification of three bacterial species associated with increased appendicular lean mass: the HUNT study.

Appendicular lean mass (ALM) associates with mobility and bone mineral density (BMD). While associations between gut microbiota composition and ALM have been reported, previous studies rely on relatively small sample sizes. Here, we determine the associations between prevalent gut microbes and ALM in large discovery and replication cohorts with information on relevant confounders within the population-based Norwegian HUNT cohort (n = 5196, including women and men). We show that the presence of three bacterial species - Coprococcus comes, Dorea longicatena, and Eubacterium ventriosum - are reproducibly associated with higher ALM. When combined into an anabolic species count, participants with all three anabolic species have 0.80 kg higher ALM than those without any. In an exploratory analysis, the anabolic species count is positively associated with femoral neck and total hip BMD. We conclude that the anabolic species count may be used as a marker of ALM and BMD. The therapeutic potential of these anabolic species to prevent sarcopenia and osteoporosis needs to be determined.

Maternal and Early-Life Exposure to Antibiotics and the Risk of Autism and Attention-Deficit Hyperactivity Disorder in Childhood: a Swedish Population-Based Cohort Study.

INTRODUCTION: Antibiotics represent the most common type of medication used during pregnancy and infancy. Antibiotics have been proposed as a possible factor in changes in microbiota composition, which may play a role in the aetiology of autism and attention deficit/hyperactivity disorder (ADHD). Our aim was to investigate the association between maternal and early-life antibiotic use and autism and ADHD in childhood. METHODS: This Swedish nation-wide population-based cohort study included all first live singleton births (N = 483,459) between January 2006 and December 2016. The association of dispensed antibiotics with autism and ADHD in children aged ≤ 11 years was estimated by applying multivariable logistic regression and generalised estimating equations models. RESULTS: Of the mothers, 25.9% (n = 125,106) were dispensed ≥1 antibiotic during the exposure period (from 3 months pre-conception to delivery), and 41.6% (n = 201,040) of the children received ≥ 1 antibiotic in early life (aged ≤ 2 years). Penicillin was the most prescribed antibiotic class (17.9% of mothers, 38.2% of children). Maternal antibiotic use was associated with an increased risk of autism [odds ratio (OR) = 1.16, 95% confidence interval (CI) 1.09-1.23] and ADHD (OR = 1.29, 95% CI 1.21-1.36) in childhood. Early-life exposure to antibiotics showed an even stronger association [autism (OR = 1.46, 95% CI 1.38-1.55); ADHD (OR = 1.90, 95% CI 1.80-2.00)]. Both maternal and childhood-exposure sub-analyses suggested a dose-response relationship. CONCLUSION: Maternal and early-life antibiotic use was associated with an increased risk of autism and ADHD in childhood. However, differences were noted by exposure period and antibiotic classes.

Antibiotics are commonly prescribed to pregnant women, infants, and toddlers. Antibiotic use during pregnancy may alter the maternal microbiota, which can influence the microbial colonisation of the gastrointestinal system of the foetus. It has been claimed that antibiotic use during pregnancy may have an effect on the gut-brain axis and, as a result, neurodevelopment. Neurodevelopmental disorder (NDD) is a category of illnesses characterised by functional impairments that manifest early in development. The most frequent NDDs are autism and attention-deficit/hyperactivity disorder (ADHD). In this large Swedish nation-wide study, we assessed whether antibiotic use during pregnancy and/or early in life affects the risk of developing autism and ADHD. The study found that both maternal antibiotic usage, as well as early childhood antibiotic use, were associated with an increased risk of autism and ADHD in children. These associations were altered by the quantity, type, and timing of antibiotic exposure.

Sensitive quantification of short-chain fatty acids combined with global metabolomics in microbiome cultures.

The microbiome has been identified to have a key role for the physiology of their human host. One of the major impacts is the clearance of bacterial pathogens. We have now developed a chemoselective probe methodology for the absolute quantification of short-chain fatty acids at low nM concentrations, with high reproducibility and spiked isotope labelled internal standards. Immobilization to magnetic beads allows for separation from the matrix and the tagged metabolites upon bioorthogonal cleavage can be analyzed via UHPLC-MS. The major advantage of our sensitive method is the simple combination with global metabolomics analysis as only a small sample volume is required. We have applied this chemical metabolomics strategy for targeted SCFA analysis combined with global metabolomics on gut microbiome co-cultures with Salmonella and investigated the effect of antibiotic treatment.

Diverticulosis is not associated with altered gut microbiota nor is it predictive of future diverticulitis: a population-based colonoscopy study.

BACKGROUND: The etiopathogenesis of diverticular disease is unknown. OBJECTIVE: To compare the fecal and mucosa-associated microbiota between participants with and without diverticulosis and participants who later developed diverticulitis versus those that did not from a population-based study. METHODS: The PopCol study, conducted in Stockholm, Sweden, invited a random sample of 3556 adults to participate, of which 745 underwent colonoscopy. Overall, 130 participants (17.5%) had diverticulosis. 16S rRNA gene sequencing was conducted on available sigmoid biopsy samples from 529 and fecal samples from 251 individuals. We identified individuals who subsequently developed acute diverticulitis up to 13 years after sample collection. In a case-control design matching for gender, age (+/-5 years), smoking and antibiotic exposure, we compared taxonomic composition, richness and diversity of the microbiota between participants with or without diverticulosis, and between participants who later developed acute diverticulitis versus those who did not. RESULTS: No differences in microbiota richness or diversity were observed between participants with or without diverticulosis, nor for those who developed diverticulitis compared with those who did not. No bacterial taxa were significantly different between participants with diverticulosis compared with those without diverticulosis. Individuals who later developed acute diverticulitis (2.8%) had a higher abundance of genus Comamonas than those who did not (p = .027). CONCLUSIONS: In a population-based cohort study the only significant difference was that those who later develop diverticulitis had more abundance of genus Comamonas. The significance of Comamonas is unclear, suggesting a limited role for the gut microbiota in the etiopathogenesis of diverticular disease.