The intestinal microbiota is integral to host health, metabolism, and colonization resistance. Antibiotics can disrupt microbial homeostasis, leading to dysbiosis and altered colonization resistance. While antibiotic-induced microbiota disruption is well-documented, less is known about how host genetics shapes post-antibiotic recovery. Here, we investigate the impact of B4galnt2, a blood-group-related glycosyltransferase gene, on microbiota recovery following antibiotic treatment. Using a longitudinal, multi-omic approach-including 16S rRNA gene sequencing, metagenomics, and metatranscriptomics-we compare the microbiota dynamics of B4galnt2+/- and B4galnt2-/- mice after treatment with streptomycin, kanamycin, and vancomycin. Our findings reveal that B4galnt2-/- mice exhibit faster recovery of microbial diversity and composition following streptomycin treatment compared to their B4galnt2+/- counterparts. This accelerated recovery is associated with higher relative abundance of taxa such as Blautia, Dorea, and other Lachnospiraceae, and increased expression of motility-related genes, and differential regulation of antibiotic resistance genes (ARGs), including the aminoglycoside nucleotidyltransferase genes aadA and aadE. Genotype-dependent differences in recovery were most pronounced following streptomycin and were not consistently observed with kanamycin or vancomycin, indicating an antibiotic-by-genotype interaction shaped by the B4galnt2-associated microbiota. These results underscore the role of host genetics in shaping microbiota response and recovery following antibiotic exposure. By demonstrating the interplay between glycosylation-mediated microbiota composition, antibiotic response, and microbial recovery, our study may provide insights into the potential for personalized approaches to mitigate dysbiosis-related health outcomes. IMPORTANCE:Antibiotic treatments disrupt the gut microbiome, often leading to long-term alterations that potentially affect host health. While much is known about how antibiotics cause microbial dysbiosis, little is understood about the factors that could influence the speed of microbial community recovery, such as host genetic differences. Using a mouse model, this study reveals that genetic variation at the blood group-related B4galnt2 gene significantly alters recovery after streptomycin treatment. Mice lacking intestinal B4galnt2 expression recover faster, with distinct changes in microbial composition, activity, and antibiotic resistance gene expression. These findings highlight how a single host gene can shape microbiota dynamics following antibiotic-induced disruption. The work emphasizes the importance of considering host genetic factors when predicting microbiome responses to antibiotics and suggests potential for genotype-guided strategies to reduce the adverse effects of microbiome-targeted therapies.

Diets based on dairy or seafood proteins are reported to be less obesogenic than diets based on terrestrial meat proteins. The metabolic pathways underlying these differences, including processes related to thermogenesis, remain incompletely understood. Here, we investigated responses at levels of the transcriptome and the metabolome associated with potentially obesogenic high-fat, high-protein diets using casein, cod, or chicken as protein sources in mice kept at thermoneutral conditions or room temperature to evaluate metabolic responses to different housing temperatures. By performing plasma metabolomics analyses combined with RNA sequencing and gene set enrichment analyses of liver, muscle, white- and brown adipose tissue, we aimed to decipher the metabolic output and pathways modulated by intake of different dietary proteins. Dietary protein intake of casein, cod, or chicken led to differences in obesity development independent of housing temperature. The diet-specific phenotype was associated with a distinct plasma lipid profile and transcriptomic profile in liver and adipose tissue. One-carbon metabolism emerged as a potentially affected key pathway, and the mechanistic target of rapamycin complex 1/2 appeared as a predicted upstream regulator and accordingly suggested to be associated with protein source-dependent differences in obesity development and related metabolic disturbances.

The prospective Kiel Inflammatory Bowel Disease (IBD) Family Cohort Study (KINDRED cohort) was initiated in 2013 to systematically and extensively collect data and biosamples from index IBD patients and their relatives, a population at high risk for IBD development. Regular follow-ups were conducted to collect updated health and lifestyle information, to obtain new biosamples, and to capture the incidence of IBD during development. By combining microbial data collected at successive time points with extensive anthropometric, medical, nutritional, and social information, this study aimed to characterize the factors influencing the microbiota in health and disease via detailed ecological analyses. Using a microbial dysbiosis metric based on the German KINDRED cohort, we identified strong and generalizable gradients within and across different external IBD cohorts for validation. These community gradients correspond strongly with IBD pathologies, physiological manifestations of inflammation (e.g. Bristol stool score, ASCA IgA, ASCA IgG), and genetic risk for IBD. Anthropometric and medical factors influencing fecal transit time strongly modify bacterial communities. Various Enterobacteriaceae (e.g. Klebsiella sp.) and opportunistic Clostridia pathogens (e.g. C. XIVa clostridioforme), characterize in combination with ectopically colonizing oral taxa (e.g. Veillonella sp. Cand. Saccharibacteria sp. Fusobacterium nucleatum) the distinct and chaotic IBD-specific communities. Weak community and physiological changes are further traceable in a small number of individuals, who developed IBD in the study's runtime. Our findings demonstrate broad-scale ecological patterns which indicate drastic state transitions of communities in IBD patients. These patterns appear to be universal across cohorts and influence physiological signs of inflammation, display increased resilience, but show only limited heritability/intrafamily transmission.

Metaorganism research contributes substantially to our understanding of the interaction between microbes and their hosts, as well as their co-evolution. Most research is currently focused on the bacterial community, while archaea often remain at the sidelines of metaorganism-related research. Here, we describe the archaeome of a total of eleven classical and emerging multicellular model organisms across the phylogenetic tree of life. To determine the microbial community composition of each host, we utilized a combination of archaea and bacteria-specific 16S rRNA gene amplicons. Members of the two prokaryotic domains were described regarding their community composition, diversity, and richness in each multicellular host. Moreover, association with specific hosts and possible interaction partners between the bacterial and archaeal communities were determined for the marine models. Our data show that the archaeome in marine hosts predominantly consists of Nitrosopumilaceae and Nanoarchaeota, which represent keystone taxa among the porifera. The presence of an archaeome in the terrestrial hosts varies substantially. With respect to abundant archaeal taxa, they harbor a higher proportion of methanoarchaea over the aquatic environment. We find that the archaeal community is much less diverse than its bacterial counterpart. Archaeal amplicon sequence variants are usually host-specific, suggesting adaptation through co-evolution with the host. While bacterial richness was higher in the aquatic than the terrestrial hosts, a significant difference in diversity and richness between these groups could not be observed in the archaeal dataset. Our data show a large proportion of unclassifiable archaeal taxa, highlighting the need for improved cultivation efforts and expanded databases.

OBJECTIVE:Patients with Crohn's disease (CD) exhibit great heterogeneity in disease presentation and treatment responses, where distinct gut bacteria and immune interactions may play part in the yet unresolved disease aetiology. Given the role of antibodies in the barrier defence against microbes, we hypothesised that gut bacterial antibody-coating patterns may influence underlying disease-mediated processes. DESIGN:Absolute and relative single and multicoating of gut bacteria with IgA, IgG1, IgG2, IgG3 and IgG4 in patients with CD and healthy controls were characterised and compared with disease activity. IgG2-coated and non-coated taxa from patients with severe CD were identified, profiled for pathogenic characteristics and monitored for enrichment during active disease across cohorts. RESULTS:Patients with severe CD exhibited higher gut bacterial IgG2-coating. Supervised clustering identified 25 bacteria to be enriched in CD patients with high IgG2-coating. Sorting, sequencing and in silico-based assessments of the virulent potential of IgG2-coated and bulk stool bacteria were performed to evaluate the nature and pathogenicity of IgG2-coated and non-coated bacteria. The analyses demonstrated IgG2-coating of both known pathogenic and non-pathogenic bacteria that co-occurred with two non-coated pathobionts, Campylobacter and Mannheimia. The two non-coated pathobionts exhibited low prevalence, rarely coincided and were strongly enriched during disease flares in patients with CD across independent and geographically distant cohorts. CONCLUSION:Distinct gut bacterial IgG2-coating was demonstrated in patients with severe CD and during disease flares. Co-occurrence of non-coated pathobionts with IgG2-coated bacteria points to an uncontrolled inflammatory condition in severe CD mediated via escape from antibody coating by two gut pathobionts.

Inflammatory bowel disease (IBD) is associated with dysbiotic microbiomes. However, whether microbiomes of family members of IBD patients harbour microbial disease signatures of IBD is unknown. Here, we generate shotgun metagenomic data of an IBD family cohort and treatment-naive IBD cases, which we combine with published IBD metagenomes, to perform a meta-analysis of IBD-microbiome associations. Our study reveals microbial shifts that are specific to IBD or IBD subtypes (Crohn’s disease and ulcerative colitis). We find that IBD cohorts share signatures of association with disease irrespective of geography, and we report novel species-level identifications of microbial taxa that are universal markers of Crohn’s disease. We further demonstrate that the microbiome of healthy family members at high risk for IBD represent transitional states between the microbiome of unrelated healthy controls and IBD cases, and harbor diversity, compositional and ecological features that are also observed among IBD microbiomes. Overall, our study provides valuable insights into the intricate relationship between the gut microbiome and IBD, with implications for better predicting disease onset among individuals with high susceptibility for IBD. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was financed through the EU Horizon miGut-Health project (Personalised blueprint of chronic inflammation in health-to-disease transition; Grant agreement ID: 101095470, AF, MG) and the DFG-sequencing grant Identification of early fine-scale microbial signatures in inflammatory bowel disease (project 433152305, CB, AF, WL). Microbiome sequencing and data analysis received infrastructure support from the DFG Excellence Cluster 2167 (Precision Medicine in Chronic Inflammation (PMI)) and the DFG Research Unit 5042 miTarget. MR was supported by the Bruhn foundation for the advancement of medical research. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee of the Medical Faculty of Kiel University gave ethical approval for this work (AZ A117/13 & AZ A103/14) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data and material of the IBD-FC cohort are available upon the submission of a research proposal to https://portal.popgen.de/. Data of the ITM cohort will be uploaded to ENA upon acceptance of this manuscript at a peer-reviewed journal.

Abstract Background Microbial communities have long been suspected to influence inflammatory processes in the gastrointestinal tract of patients with inflammatory bowel disease. However, these effects are often influenced by treatments and can rarely be analyzed in treatment-naïve onset cases. Specifically, microbial differences between IBD pathologies in new onset cases have rarely been investigated and can provide novel insight into the dynamics of the microbiota in Crohn’s disease (CD) and ulcerative colitis (UC). Methods Fifty-six treatment-naïve IBD onset patients (67.3% CD, 32.7% UC) and 97 healthy controls were recruited from the Maltese population. Stool samples were collected after diagnosis but before administration of anti-inflammatory treatments. Fecal microbial communities were assessed via 16S rRNA gene sequencing and subjected to ecological analyses to determine disease-specific differences between pathologies and disease subtypes or to predict future treatment options. Results We identified significant differences in community composition, variability, and diversity between healthy and diseased individuals—but only small to no differences between the newly diagnosed, treatment-naïve UC and CD cohorts. Network analyses revealed massive turnover of bacterial interactions between healthy and diseased communities, as well as between CD and UC communities, as signs of disease-specific changes of community dynamics. Furthermore, we identified taxa and community characteristics serving as predictors for prospective treatments. Conclusion Untreated and newly diagnosed IBD shows clear differences from healthy microbial communities and an elevated level of disturbance, but only the network perspective revealed differences between pathologies. Furthermore, future IBD treatment is to some extent predictable by microbial community characteristics.

Background and Objectives Anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) is the most common form of autoimmune encephalitis in children and adults. Although our understanding of the disease mechanisms has progressed, little is known about estimating patient outcomes. Therefore, the NEOS (anti-NMDAR Encephalitis One-Year Functional Status) score was introduced as a tool to predict disease progression in NMDARE. Developed in a mixed-age cohort, it currently remains unclear whether NEOS can be optimized for pediatric NMDARE. Methods This retrospective observational study aimed to validate NEOS in a large pediatric-only cohort of 59 patients (median age of 8 years). We reconstructed the original score, adapted it, evaluated additional variables, and assessed its predictive power (median follow-up of 20 months). Generalized linear regression models were used to examine predictability of binary outcomes based on the modified Rankin Scale (mRS). In addition, neuropsychological test results were investigated as alternative cognitive outcome. Results The NEOS score reliably predicted poor clinical outcome (mRS ≥3) in children in the first year after diagnosis (p = 0.0014) and beyond (p = 0.036, 16 months after diagnosis). A score adapted to the pediatric cohort by adjusting the cutoffs of the 5 NEOS components did not improve predictive power. In addition to these 5 variables, further patient characteristics such as the "Herpes simplex virus encephalitis (HSE) status" and "age at disease onset" influenced predictability and could potentially be useful to define risk groups. NEOS also predicted cognitive outcome with higher scores associated with deficits of executive function (p = 0.048) and memory (p = 0.043). Discussion Our data support the applicability of the NEOS score in children with NMDARE. Although not yet validated in prospective studies, NEOS also predicted cognitive impairment in our cohort. Consequently, the score could help identify patients at risk of poor overall clinical outcome and poor cognitive outcome and thus aid in selecting not only optimized initial therapies for these patients but also cognitive rehabilitation to improve long-term outcomes.

Microbial communities in the intestinal tract are suggested to impact the ethiopathogenesis of Alzheimer's disease (AD). The human microbiome might modulate neuroinflammatory processes and contribute to neurodegeneration in AD. However, the microbial compositions in patients with AD at different stages of the disease are still not fully characterized. We used 16S rRNA analyses to investigate the oral and fecal microbiota in patients with AD and mild cognitive impairment (MCI; n = 84), at-risk individuals (APOE4 carriers; n = 17), and healthy controls (n = 50) and investigated the relationship of microbial communities and disease-specific markers via multivariate- and network-based approaches. We found a slightly decreased diversity in the fecal microbiota of patients with AD (average Chao1 diversity for AD = 212 [SD = 66]; for controls = 215 [SD = 55]) and identified differences in bacterial abundances including Bacteroidetes, Ruminococcus, Sutterella, and Porphyromonadaceae. The diversity in the oral microbiota was increased in patients with AD and at-risk individuals (average Chao1 diversity for AD = 174 [SD = 60], for at-risk group = 195 [SD = 49]). Gram-negative proinflammatory bacteria including Haemophilus, Neisseria, Actinobacillus, and Porphyromonas were dominant oral bacteria in patients with AD and MCI and the abundance correlated with the cerebrospinal fluid biomarker. Taken together, we observed a strong shift in the fecal and the oral communities of patients with AD already prominent in prodromal and, in case of the oral microbiota, in at-risk stages. This indicates stage-dependent alterations in oral and fecal microbiota in AD which may contribute to the pathogenesis via a facilitated intestinal and systemic inflammation leading to neuroinflammation and neurodegeneration.

SCOPE:The gut microbiome regulates various metabolic pathways in the host and its dysbiosis is involved in the pathogenesis of diverse diseases. One of the major factors triggering gut microbiome establishment is diet. This study aims to unravel interactions and changes between diet and gut microbiome over a period of 3 years. METHODS AND RESULTS:This study investigates the relation between diet and the microbiome of 75 individuals over a 3-year time period. Shotgun metagenomic sequencing is performed to profile gut microbial composition and function. This study shows that there are significant changes in gut microbiome taxonomy and functional composition between two time points. Whereas microbial taxonomy is found to be highly individualized, overall microbial functions stay relatively stable. Moreover, in silico metabolic modeling of microbial communities indicates that changes in dietary intake of medium-chain saturated fatty acids is accompanied by an altered utilization of amino acids by the gut microbiome. CONCLUSION:The study design allows us to validate functional stability within the gut microbiome of healthy subjects over a 3-year period. However, enduring changes in nutrition such as increased alcohol consumption or decreased intake of vegetables come along with enhanced microbial functions that are associated with disease etiology.

Background Human well-being has been linked to the composition and functional capacity of the intestinal microbiota. As regular exercise is known to improve human health, it is not surprising that exercise was previously described to positively modulate the gut microbiota, too. However, most previous studies mainly focused on either elite athletes or animal models. Thus, we conducted a randomised intervention study that focused on the effects of different types of training (endurance and strength) in previously physically inactive, healthy adults in comparison to controls that did not perform regular exercise. Overall study duration was ten weeks including six weeks of intervention period. In addition to 16S rRNA gene amplicon sequencing of longitudinally sampled faecal material of participants (six time points), detailed body composition measurements and analysis of blood samples (at baseline and after the intervention) were performed to obtain overall physiological changes within the intervention period. Activity tracker devices (wrist-band wearables) provided activity status and sleeping patterns of participants as well as exercise intensity and heart measurements. Results Different biometric responses between endurance and strength activities were identified, such as a significant increase of lymphocytes and decrease of mean corpuscular haemoglobin concentration (MCHC) only within the strength intervention group. In the endurance group, we observed a significant reduction in hip circumference and an increase in physical working capacity (PWC). Though a large variation of microbiota changes were observed between individuals of the same group, we did not find specific collective alterations in the endurance nor the strength groups, arguing for microbiome variations specific to individuals, and therefore, were not captured in our analysis. Conclusions We could show that different types of exercise have distinct but moderate effects on the overall physiology of humans and very distinct microbial changes in the gut. The observed overall changes during the intervention highlight the importance of physical activity on well-being. Future studies should investigate the effect of exercise on a longer timescale, investigate different training intensities and consider high-resolution shotgun metagenomics technology. Trial registration DRKS, DRKS00015873 . Registered 12 December 2018; Retrospectively registered.

Abstract Background The role of microbiome with the alteration between commensal and pathogenic bacteria, has been linked to IBD. Meanwhile Escherichia coli Nissle 1917, Lactobacillus rhamnosus GG (LGG) and faecal transplantation are used in IBD. The aim of this study was to prospectively determine faecal microbiota composition of newly diagnosed treatment naïve IBD patients. Methods Patients diagnosed with IBD between January 2018-September 2019 were recruited. Clinical data was collected and patients asked to submit stool samples for microbiome analysis. Stool samples from a control population were recruited and analysed via the bacterial 16s rRNA gene sequencing on illumine MiSeq. Results 100 IBD patients (CD: n=46, UC: n=53 & IBDU: n=1) and 97 controls with specific inclusion and exclusion criteria collected. IBD patients were noted to display reduced average species richness and community evenness compared to healthy controls (Alpha- Diversity) (Figure 1). Beta-diversity between microbial communities of healthy individuals and IBD patients was significantly different, but no observed separation between the two types of IBD was noted (Figure 2). 11 ASVs were abundant in CD patients including: ASV-70 – Lactobacillus gasseri, Klebsiella uncl., Candidatus-saccharibacteria, ASV-157 - Acteroides clarus and ASV 249- Parasutterella uncl. In UC cohort, 10 ASVs were abundant including: ASV 6-Escherichia/Shigella uncl., ASB-41-Sutterella wadsworthensis, ASV 44- Bacteroides faecis and Actinobacteria. An association between UC and ASV 313 (Faecalibacteria) was present. In the microbiome of healthy controls, 20 ASVs were abundant, including: ASV-14 G-Alistipes uncl., ASV 20-(Akkermansia muciniphila),(bacterium belonging to the phylum Verrucomicrobia), ASV 321 (Clostridia uncl.), ASV 96 (Rumminococcaceae uncl.), Alistepes uncl. (ASV 61), Subdoligranulum uncl. (ASV 453) and the unclassifiable bacteria. A higher amount of Verrucomicrobia was present in the healthy group as opposed to the IBD. Conclusion ASV 249- Parasutterella unlc., was indicative of CD associated microbiome through the indicator species analysis. Typical microbiome changes in IBD patients include increased abundance of the pro-inflammatory species with a reduction in anti-inflammatory bacterial species, with a noticeable reduction in alpha and beta diversity. In the local cohort, a particular change in the local α- and β diversity was noted to be present between healthy controls and IBD cohort. This could be a potential way in which targeted therapeutic approaches using specific dosage and durations of probiotic or faecal transplant can be used to alter faecal microbiome using specific bacteria present in healthy controls and with elimination of potentially harmful bacteria in IBD patients. Figure 1: Alpha diversity between different Groups using Chao1 species richness and Simpson 1-D Figure 2: Beta diversity between different groups using Bray-Curtis dissimilarity, Jaccard distance.

Abstract Background Correlation networks are employed to assess the interactions between different bacteria. The aim of this study was to assess which bacterial species had central positions in a network analysis in faecal samples of patients with IBD who are in remission. Methods The fecal microbiota of 98 Maltese patients with IBD who were in remission and a control group (97 controls) were analyzed by 16S rRNA sequencing. To generate co-abundance networks the SparCC algorithm as implemented in mothur was employed (50 samplings, 100 iterations, 10,000 permutations) based on Amplicon sequence variants (ASV) abundances (shared among 10% samples) at a P-value cutoff of PFDR≤0.05 and a correlation strength above the median of non-zero correlations. Results Correlation network analysis identified two flavonoid-degrading bacteria to be more important than expected by chance. Flavonifractor plautii (previously known as Clostridium Orbiscindens and Eubacterium plautii) which associated to IBD more than to controls and Eggertella lenta, which associated to patients with Ulcerative colitis (UC), had a high network importance on several levels, with a very central position (betweenness) and many associations to other community members (node degree), which are themselves important mediators (PageRank®) (Figure 1) Other bacteria occupying highly central positions in the community network included Oscillibacter uncl., Alistipes shahii and members of the order Clostridiales. These associated to controls and are known butyrate producers, usually associated with a beneficial effect on gut homeostasis. Eigenvalue centrality identified a strongly correlated group of Enterobacteriaceae. Figure 1: The barplots show the top 50 bacteria within the network based on their centrality measures (Betweenness, Degree, Eigenvalue centrality, PageRank). Highlighted in red are network members with a higher importance than expected by chance, based on a Z-test against 10’000 randomized networks (P ≤ 0.05). Highlighted as well are the associations of the respective ASVs to various factors, as detected by indicator species analysis (p≤0.05). Conclusion Flavonoids have been described to have anti-inflammatory properties and flavonoid-degrading bacteria have been associated with the prevention of malignancy, cardiovascular disease, diabetes type 2 and cognitive decline. In mice studies, oral administration of Flavinofractor plautii was noted to suppress Th2 immune responses. Thus, one may postulate that their presence may be important in the maintenance of IBD, although in a state of remission. Future studies should provide more evidence on their role and whether the colonization of flavonoid degrading bacteria can induce remission or conversely increase chronicity or severity of IBD.

Little is known about the involvement of type 2 immune response-promoting intestinal tuft cells in metabolic regulation. We here examined the temporal changes in small intestinal tuft cell number and activity in response to high-fat diet-induced obesity in mice and investigated the relation to whole-body energy metabolism and the immune phenotype of the small intestine and epididymal white adipose tissue. Intake of high fat diet resulted in a reduction in overall numbers of small intestinal epithelial and tuft cells and reduced expression of the intestinal type 2 tuft cell markers Il25 and Tslp. Amongst >1,700 diet-regulated transcripts in tuft cells, we observed an early association between body mass expansion and increased expression of the gene encoding the serine protease inhibitor neuroserpin. By contrast, tuft cell expression of genes encoding gamma aminobutyric acid (GABA)-receptors was coupled to Tslp and Il25 and reduced body mass gain. Combined, our results point to a possible role for small intestinal tuft cells in energy metabolism via coupled regulation of tuft cell type 2 markers and GABA signaling receptors, while being independent of type 2 immune cell involvement. These results pave the way for further studies into interventions that elicit anti-obesogenic circuits via small intestinal tuft cells.

Compared to the huge microbial diversity in most mammals, human gut microbiomes have lost diversity while becoming specialized for animal-based diets – especially compared to chimps, their genetically closest ancestors. The lowered microbial diversity within the gut of westernized populations has also been associated with different kinds of chronic inflammatory diseases in humans. To further deepen our knowledge on phylogenetic and ecologic impacts on human health and fitness, we established the herein presented biobank as well as its comprehensive microbiota analysis. In total, 368 stool samples from 38 different animal species, including Homo sapiens, belonging to four diverse mammalian orders were collected at seven different locations and analyzed by 16S rRNA gene amplicon sequencing. Comprehensive data analysis was performed to (i) determine the overall impact of host phylogeny vs. diet, location, and ecology and to (ii) examine the general pattern of fecal bacterial diversity across captive mammals

Abstract Background Members of the Enterobacteriaceae have been associated with active Crohn’s Disease (CD), possibly as a result of intestinal inflammation via production of a lipopolysaccharide that can trigger TLR4 signalling. This study aims to assess whether this association persists in remission of CD patients and whether correlation with disease phenotype is present. Methods Stool samples of 32 CD patients in remission and 97 healthy controls were analyzed by 16S rRNA sequencing. High quality Amplicon sequence variants (ASV) were derived and classified via DADA2. Results ASV 6-Escherichia/Shigella uncl. was found to be more abundant in CD (padj=0.0003) while ASV 24, another member of the Escherichia/Shigella cluster was identified as being an indicator species for CD (padj=0.09). Differential abundance analysis according to phenotype as per Montreal classification revealed that, compared to patients with the B1 phenotype, patients with the B2 and/or B3 have a higher abundance of Escherichia/Shigella uncl. (ASVs 13, 31, 282 and 422), Klebsiella uncl. (ASVs 75 and 101) and Enterobacter uncl. (ASV 219) (Figure 1). Furthermore, patients with L3 involvement had higher abundances of Klebsiella uncl. (ASVs 75 and 101) and Parasutturella uncl. (ASVs 22, 53, 120, 199, 249 and 510), the latter being a Proteobacteria, compared to patients with L1 and/or L2 involvement. No significant association with “Age of Onset” was identified. In addition, network analyses revealed a strongly correlated group of Enterobacteriaceae ASVs (Klebsiella, Escherichia/Shigella, Enterobacter, Citrobacter) which appear to collectively associate to CD. Abstract DOP25 – Figure 1: Heatmap visualizing significant differentially abundant ASVs in CD patients with respect to behaviour subgroups Conclusion Enterobacteriaceae persist in the faecal microbiota in significantly higher levels than controls despite remission and furthermore are associated with the more severe phenotypes of stricturing and penetrating disease. Further studies might indicate whether microbiota assessment on diagnosis might predict CD subtypes and therefore influence therapeutic choices.

Dysbiosis in inflammatory bowel disease (IBD) has been implicated as a causal or contributory factor to the pathogenesis of the disease. This study, done on patients in remission while accounting for various confounding factors, shows significant community differences and altered community dynamics, even after acute inflammation has subsided.

Abstract Background Comprehensive knowledge of the types and ratios of microbes present in the healthy gastrointestinal human gut is required before any study is attempted to alter the microbiome to treat one condition. Akkermansia muciniphila, a mucin-degrading bacterium, belonging to the phylum Verrucomicrobia, has been inversely associated with inflammation and diabetes whilst it has been internationally proposed as one of the contributors for maintaining a healthy gut and glucose homeostasis. Studies noted that higher amounts of this microorganism in the gut microbiota was linked to a metabolically healthier lifestyle; therefore, linking an interaction between the gut bacterial richness and abundance of A. muciniphila. This organism was noted to improve the gut barrier using its outer membrane protein Amuc 1100, which seems to interact with Toll-like receptor 2, whilst potentially adhering to intestinal epithelial cells, leading its role in balancing the human immunological homeostasis whilst strengthening the monolayer integrity of the wall. The aim of this study was to assess if there is any difference in the presence of Akkermansia muciniphila between IBD patients and controls. Methods Faecal microbiota from newly diagnosed treatment naïve IBD patients and controls were analysed via the bacterial 16s rRNA gene sequencing on illumine MiSeq. Results 100 patients with IBD and 97 controls were recruited. Forty-one different ASVs were identified from our cohort, all of which being differentially abundant between the different health conditions present. From these, 20 ASVs such as ASV-14 G-Alistipes uncl., and ASV 20-Akkermansia muciniphila, were found to be more abundant in healthy individuals than in IBD patients. There was no dietary association. Conclusion In this study Akkermansia muciniphila was significantly found in higher amount in the healthy control population than in the IBD cohort. The potential role of repopulating the gut bacteria with Akkermansia muciniphila needs to be investigated as to reduce the burden of disease, medications prescribed and the clinical outcome.

The microbiota and the gastrointestinal mucus layer play a pivotal role in protection against non-typhoidal Salmonella enterica serovar Typhimurium (S. Tm) colitis. Here, we analyzed the course of Salmonella colitis in mice lacking a functional mucus layer in the gut. Unexpectedly, in contrast to mucus-proficient littermates, genetically deficient mice were protected against Salmonellainduced gut inflammation in the streptomycin colitis model. This correlated with microbiota alterations and enrichment of the bacterial phylum Deferribacteres. Using gnotobiotic mice associated with defined bacterial consortia, we causally linked Mucispirillum schaedleri, currently the sole known representative of Deferribacteres present in the mammalian microbiota, to host protection against S. Tm colitis. Inhibition by M. schaedleri involves interference with S. Tm invasion gene expression, partly by competing for anaerobic electron acceptors. In conclusion, this study establishes M. schaedleri, a core member of the murine gut microbiota, as a key antagonist of S. Tm virulence in the gut.