TY  - JOUR
AB  - Bile acids (BAs) undergo extensive microbial metabolism in the gut and exert hormone-like functions on physiological processes underlying metabolic risk. However, the extent to which gut BA profiles predict cardiometabolic risk and explain individual responses to dietary interventions in humans is still unclear. In the DIRECT-PLUS Trial, we conducted a multi-omics analysis of 284 participants randomized into three groups: healthy dietary guidelines and two Mediterranean diet (MedDiet) groups. We longitudinally measured 44 fecal BAs using liquid chromatography-mass spectrometry, the gut microbiome through shotgun metagenomic sequencing, and body adiposity and serum lipids at baseline, 6, and 18 months. Fecal levels of 14 BAs, such as lithocholic acid and ursodeoxycholic acid, were prospectively associated with body mass index (BMI) and serum lipid profiles (false discovery rate [q]<0.05). Baseline fecal BA levels significantly modified the beneficial effects of the MedDiet; for example, BMI reduction induced by MedDiet interventions was more pronounced in individuals with lower 12-dehydrocholic acid levels (q-interaction <0.001). We confirmed that the gut microbiome is a major modifier of the secondary BA pool in humans. Furthermore, the association of fecal BAs with body adiposity and serum lipids varied significantly in individuals with different abundances of gut microbes carrying BA metabolism enzymes, e.g. several Ruminococcus spp. In summary, our study identifies novel predictive biomarkers for cardiometabolic risk and offers new mechanistic insights to guide personalized dietary interventions.
AU  - Gao, P.*
AU  - Rinott, E.*
AU  - Dong, D.*
AU  - Mei, Z.*
AU  - Wang, F.*
AU  - Liu, Y.*
AU  - Kamer, O.*
AU  - Yaskolka Meir, A.*
AU  - Tuohy, K.M.*
AU  - Blüher, M.
AU  - Stumvoll, M.
AU  - Stampfer, M.J.*
AU  - Shai, I.*
AU  - Wang, D.D.*
C1  - 72293
C2  - 56553
TI  - Gut microbial metabolism of bile acids modifies the effect of Mediterranean diet interventions on cardiometabolic risk in a randomized controlled trial.
JO  - Gut Microbes
VL  - 16
IS  - 1
PY  - 2024
SN  - 1949-0976
ER  - 

TY  - JOUR
AB  - Gut microbiota-derived metabolites play a pivotal role in the maintenance of intestinal immune homeostasis. Here, we demonstrate that the human commensal Clostridium sporogenes possesses a specific metabolic fingerprint, consisting predominantly of the tryptophan catabolite indole-3-propionic acid (IPA), the branched-chain acids (BCFAs) isobutyrate and isovalerate and the short-chain fatty acids (SCFAs) acetate and propionate. Mono-colonization of germ-free mice with C. sporogenes (CS mice) affected colonic mucosal immune cell phenotypes, including up-regulation of Il22 gene expression, and increased abundance of transcriptionally active colonic tuft cells and Foxp3+ regulatory T cells (Tregs). In DSS-induced colitis, conventional mice suffered severe inflammation accompanied by loss of colonic crypts. These symptoms were absent in CS mice. In conventional, but not CS mice, bulk RNAseq analysis of the colon revealed an increase in inflammatory and Th17-related gene signatures. C. sporogenes-derived IPA reduced IL-17A protein expression by suppressing mTOR activity and by altering ribosome-related pathways in Th17 cells. Additionally, BCFAs and SCFAs generated by C. sporogenes enhanced the activity of Tregs and increased the production of IL-22, which led to protection from colitis. Collectively, we identified C. sporogenes as a therapeutically relevant probiotic bacterium that might be employed in patients with inflammatory bowel disease (IBD).
AU  - Krause, F.F.*
AU  - Mangold, K.I.*
AU  - Ruppert, A.L.*
AU  - Leister, H.*
AU  - Hellhund-Zingel, A.*
AU  - Lopez Krol, A.*
AU  - Pesek, J.*
AU  - Watzer, B.*
AU  - Winterberg, S.*
AU  - Raifer, H.*
AU  - Binder, K.*
AU  - Kinscherf, R.*
AU  - Walker, A.
AU  - Nockher, W.A.*
AU  - Taudte, R.V.*
AU  - Bertrams, W.*
AU  - Schmeck, B.*
AU  - Kühl, A.A.*
AU  - Siegmund, B.*
AU  - Romero, R.*
AU  - Luu, M.*
AU  - Göttig, S.*
AU  - Bekeredjian-Ding, I.*
AU  - Steinhoff, U.*
AU  - Schütz, B.*
AU  - Visekruna, A.*
C1  - 72005
C2  - 56545
TI  - Clostridium sporogenes-derived metabolites protect mice against colonic inflammation.
JO  - Gut Microbes
VL  - 16
IS  - 1
PY  - 2024
SN  - 1949-0976
ER  - 

TY  - JOUR
AB  - We previously reported that autologous-fecal-microbiota-transplantation (aFMT), following 6 m of lifestyle intervention, attenuated subsequent weight regain and insulin rebound for participants consuming a high-polyphenol green-Mediterranean diet. Here, we explored whether specific changes in the core (abundant) vs. non-core (low-abundance) gut microbiome taxa fractions during the weight-loss phase (0-6 m) were differentially associated with weight maintenance following aFMT. Eighty-two abdominally obese/dyslipidemic participants (age = 52 years; 6 m weightloss = -8.3 kg) who provided fecal samples (0 m, 6 m) were included. Frozen 6 m's fecal samples were processed into 1 g, opaque and odorless aFMT capsules. Participants were randomly assigned to receive 100 capsules containing their own fecal microbiota or placebo over 8 m-14 m in ten administrations (adherence rate > 90%). Gut microbiome composition was evaluated using shotgun metagenomic sequencing. Non-core taxa were defined as ≤ 66% prevalence across participants. Overall, 450 species were analyzed. At baseline, 13.3% were classified as core, and Firmicutes presented the highest core proportion by phylum. During 6 m weight-loss phase, abundance of non-core species changed more than core species (P < .0001). Subject-specific changes in core and non-core taxa fractions were strongly correlated (Jaccard Index; r = 0.54; P < .001). Following aFMT treatment, only participants with a low 6 m change in core taxa, and a high change in non-core taxa, avoided 8-14 m weight regain (aFMT = -0.58 ± 2.4 kg, corresponding placebo group = 3.18 ± 3.5 kg; P = .02). In a linear regression model, low core/high non-core 6 m change was the only combination that was significantly associated with attenuated 8-14 m weight regain (P = .038; P = .002 for taxa patterns/treatment intervention interaction). High change in non-core, low-abundance taxa during weight-loss might mediate aFMT treatment success for weight loss maintenance.ClinicalTrials.gov: NCT03020186.
AU  - Kamer, O.*
AU  - Rinott, E.*
AU  - Tsaban, G.*
AU  - Kaplan, A.*
AU  - Yaskolka Meir, A.*
AU  - Zelicha, H.*
AU  - Knights, D.*
AU  - Tuohy, K.*
AU  - Fava, F.*
AU  - Uwe Scholz, M.*
AU  - Ziv, O.*
AU  - Rubin, E.*
AU  - Blüher, M.
AU  - Stumvoll, M.
AU  - Ceglarek, U.*
AU  - Clément, K.*
AU  - Koren, O.*
AU  - Hu, F.B.*
AU  - Stampfer, M.J.*
AU  - Wang, D.D.*
AU  - Youngster, I.*
AU  - Shai, I.*
C1  - 68630
C2  - 54806
CY  - 530 Walnut Street, Ste 850, Philadelphia, Pa 19106 Usa
TI  - Successful weight regain attenuation by autologous fecal microbiota transplantation is associated with non-core gut microbiota changes during weight loss; randomized controlled trial.
JO  - Gut Microbes
VL  - 15
IS  - 2
PB  - Taylor & Francis Inc
PY  - 2023
SN  - 1949-0976
ER  - 

TY  - JOUR
AB  - Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide. While a close correlation between chronic Helicobacter pylori infection and CRC has been reported, the role of the virome has been overlooked. Here, we infected Apc-mutant mouse models and C57BL/6 mice with H. pylori and conducted a comprehensive metagenomics analysis of H. pylori-induced changes in lower gastrointestinal tract bacterial and viral communities. We observed an expansion of temperate phages in H. pylori infected Apc +/1638N mice at the early stage of carcinogenesis. Some of the temperate phages were predicted to infect bacteria associated with CRC, including Enterococcus faecalis. We also observed a high prevalence of virulent genes, such as flgJ, cwlJ, and sleB, encoded by temperate phages. In addition, we identified phages associated with pre-onset and onset of H. pylori-promoted carcinogenesis. Through co-occurrence network analysis, we found strong associations between the viral and bacterial communities in infected mice before the onset of carcinogenesis. These findings suggest that the expansion of temperate phages, possibly caused by prophage induction triggered by H. pylori infection, may have contributed to the development of CRC in mice by interacting with the bacterial community.
AU  - Luo, S.
AU  - Ru, J.
AU  - Mirzaei, M.K.
AU  - Xue, J.
AU  - Peng, X.
AU  - Ralser, A.*
AU  - Luque, R.M.*
AU  - Gerhard, M.*
AU  - Deng, L.
C1  - 68238
C2  - 54843
CY  - 530 Walnut Street, Ste 850, Philadelphia, Pa 19106 Usa
TI  - Gut virome profiling identifies an association between temperate phages and colorectal cancer promoted by Helicobacter pylori infection.
JO  - Gut Microbes
VL  - 15
IS  - 2
PB  - Taylor & Francis Inc
PY  - 2023
SN  - 1949-0976
ER  - 

TY  - JOUR
AB  - Bacteriophages play central roles in the maintenance and function of most ecosystems by regulating bacterial communities. Yet, our understanding of their diversity remains limited due to the lack of robust bioinformatics standards. Here we present ViroProfiler, an in-silico workflow for analyzing shotgun viral metagenomic data. ViroProfiler can be executed on a local Linux computer or cloud computing environments. It uses the containerization technique to ensure computational reproducibility and facilitate collaborative research. ViroProfiler is freely available at https://github.com/deng-lab/viroprofiler.
AU  - Ru, J.
AU  - Khan Mirzaei, M.
AU  - Xue, J.
AU  - Peng, X.
AU  - Deng, L.
C1  - 67642
C2  - 53949
CY  - 530 Walnut Street, Ste 850, Philadelphia, Pa 19106 Usa
TI  - ViroProfiler: A containerized bioinformatics pipeline for viral metagenomic data analysis.
JO  - Gut Microbes
VL  - 15
IS  - 1
PB  - Taylor & Francis Inc
PY  - 2023
SN  - 1949-0976
ER  - 

TY  - JOUR
AB  - Shigella spp. are the causative agents of bacterial dysentery and shigellosis, mainly in children living in developing countries. The study of Shigella entire life cycle in vivo and the evaluation of vaccine candidates' protective efficacy have been hampered by the lack of a suitable animal model of infection. None of the studies evaluated so far (rabbit, guinea pig, mouse) allowed the recapitulation of full shigellosis symptoms upon Shigella oral challenge. Historical reports have suggested that dysentery and scurvy are both metabolic diseases associated with ascorbate deficiency. Mammals, which are susceptible to Shigella infection (humans, non-human primates and guinea pigs) are among the few species unable to synthesize ascorbate. We optimized a low-ascorbate diet to induce moderate ascorbate deficiency, but not scurvy, in guinea pigs to investigate whether poor vitamin C status increases the progression of shigellosis. Moderate ascorbate deficiency increased shigellosis symptom severity during an extended period of time (up to 48 h) in all strains tested (Shigella sonnei, Shigella flexneri 5a, and 2a). At late time points, an important influx of neutrophils was observed both within the disrupted colonic mucosa and in the luminal compartment, although Shigella was able to disseminate deep into the organ to reach the sub-mucosal layer and the bloodstream. Moreover, we found that ascorbate deficiency also increased Shigella penetration into the colon epithelium layer in a Gulo-/- mouse infection model. The use of these new rodent models of shigellosis opens new doors for the study of both Shigella infection strategies and immune responses to Shigella infection.
AU  - Skerniskyte, J.*
AU  - Mulet, C.*
AU  - André, A.C.*
AU  - Anderson, M.C.*
AU  - Injarabian, L.*
AU  - Buck, A.
AU  - Prade, V.M.
AU  - Sansonetti, P.J.*
AU  - Reibel-Foisset, S.*
AU  - Walch, A.K.
AU  - Lebel, M.*
AU  - Lykkesfeldt, J.*
AU  - Marteyn, B.S.*
C1  - 68700
C2  - 54909
CY  - 530 Walnut Street, Ste 850, Philadelphia, Pa 19106 Usa
TI  - Ascorbate deficiency increases progression of shigellosis in guinea pigs and mice infection models.
JO  - Gut Microbes
VL  - 15
IS  - 2
PB  - Taylor & Francis Inc
PY  - 2023
SN  - 1949-0976
ER  - 

TY  - JOUR
AB  - Inflammatory bowel disease (IBD) is a persistent inflammatory condition that affects the gastrointestinal tract and presents significant challenges in its management and treatment. Despite the knowledge that within-host bacterial evolution occurs in the intestine, the disease has rarely been studied from an evolutionary perspective. In this study, we aimed to investigate the evolution of resident bacteria during intestinal inflammation and whether- and how disease-related bacterial genetic changes may present trade-offs with potential therapeutic importance. Here, we perform an in vivo evolution experiment of E. coli in a gnotobiotic mouse model of IBD, followed by multiomic analyses to identify disease-specific genetic and phenotypic changes in bacteria that evolved in an inflamed versus a non-inflamed control environment. Our results demonstrate distinct evolutionary changes in E. coli specific to inflammation, including a single nucleotide variant that independently reached high frequency in all inflamed mice. Using ex vivo fitness assays, we find that these changes are associated with a higher fitness in an inflamed environment compared to isolates derived from non-inflamed mice. Further, using large-scale phenotypic assays, we show that bacterial adaptation to inflammation results in clinically relevant phenotypes, which intriguingly include collateral sensitivity to antibiotics. Bacterial evolution in an inflamed gut yields specific genetic and phenotypic signatures. These results may serve as a basis for developing novel evolution-informed treatment approaches for patients with intestinal inflammation.
AU  - Unni, R.*
AU  - Andreani, N.A.*
AU  - Vallier, M.*
AU  - Heinzmann, S.S.
AU  - Taubenheim, J.*
AU  - Guggeis, M.A.*
AU  - Tran, F.*
AU  - Vogler, O.*
AU  - Künzel, S.*
AU  - Hövener, J.B.*
AU  - Rosenstiel, P.*
AU  - Kaleta, C.*
AU  - Dempfle, A.*
AU  - Unterweger, D.*
AU  - Baines, J.F.*
C1  - 68940
C2  - 53782
CY  - 530 Walnut Street, Ste 850, Philadelphia, Pa 19106 Usa
TI  - Evolution of E. coli in a mouse model of inflammatory bowel disease leads to a disease-specific bacterial genotype and trade-offs with clinical relevance.
JO  - Gut Microbes
VL  - 15
IS  - 2
PB  - Taylor & Francis Inc
PY  - 2023
SN  - 1949-0976
ER  - 

TY  - JOUR
AB  - There is a growing debate about the involvement of the gut microbiome in COVID-19, although it is not conclusively understood whether the microbiome has an impact on COVID-19, or vice versa, especially as analysis of amplicon data in hospitalized patients requires sophisticated cohort recruitment and integration of clinical parameters. Here, we analyzed fecal and saliva samples from SARS-CoV-2 infected and post COVID-19 patients and controls considering multiple influencing factors during hospitalization. 16S rRNA gene sequencing was performed on fecal and saliva samples from 108 COVID-19 and 22 post COVID-19 patients, 20 pneumonia controls and 26 asymptomatic controls. Patients were recruited over the first and second corona wave in Germany and detailed clinical parameters were considered. Serial samples per individual allowed intra-individual analysis. We found the gut and oral microbiota to be altered depending on number and type of COVID-19-associated complications and disease severity. The occurrence of individual complications was correlated with low-risk (e.g., Faecalibacterium prausznitzii) and high-risk bacteria (e.g., Parabacteroides ssp.). We demonstrated that a stable gut bacterial composition was associated with a favorable disease progression. Based on gut microbial profiles, we identified a model to estimate mortality in COVID-19. Gut microbiota are associated with the occurrence of complications in COVID-19 and may thereby influencing disease severity. A stable gut microbial composition may contribute to a favorable disease progression and using bacterial signatures to estimate mortality could contribute to diagnostic approaches. Importantly, we highlight challenges in the analysis of microbial data in the context of hospitalization.
AU  - Schult, D.*
AU  - Reitmeier, S.*
AU  - Koyumdzhieva, P.*
AU  - Lahmer, T.*
AU  - Middelhof, M.*
AU  - Erber, J.*
AU  - Schneider, J.*
AU  - Kager, J.*
AU  - Frolova, M.*
AU  - Horstmann, J.*
AU  - Fricke, L.*
AU  - Steiger, K.*
AU  - Jesinghaus, M.*
AU  - Janssen, K.P.*
AU  - Protzer, U.
AU  - Neuhaus, K.*
AU  - Schmid, R.M.*
AU  - Haller, D.*
AU  - Quante, M.*
C1  - 64355
C2  - 52198
CY  - 530 Walnut Street, Ste 850, Philadelphia, Pa 19106 Usa
TI  - Gut bacterial dysbiosis and instability is associated with the onset of complications and mortality in COVID-19.
JO  - Gut Microbes
VL  - 14
IS  - 1
PB  - Taylor & Francis Inc
PY  - 2022
SN  - 1949-0976
ER  - 

TY  - JOUR
AB  - Although it is generally accepted that dietary fiber is health promoting, the underlying immunological and molecular mechanisms are not well defined, especially with respect to cellulose, the most ubiquitous dietary fiber. Here, the impact of dietary cellulose on intestinal microbiota, immune responses and gene expression in health and disease was examined. Lack of dietary cellulose disrupted the age-related diversification of the intestinal microbiota, which subsequently remained in an immature state. Interestingly, one of the most affected microbial genera was Alistipes which is equipped with enzymes to degrade cellulose. Absence of cellulose changed the microbial metabolome, skewed intestinal immune responses toward inflammation, altered the gene expression of intestinal epithelial cells and mice showed increased sensitivity to colitis induction. In contrast, mice with a defined microbiota including A. finegoldii showed enhanced colonic expression of intestinal IL-22 and Reg3 gamma restoring intestinal barrier function. This study supports the epidemiological observations and adds a causal explanation for the health promoting effects of the most common biopolymer on earth.
AU  - Fischer, F.*
AU  - Romero, R.*
AU  - Hellhund, A.*
AU  - Linne, U.*
AU  - Bertrams, W.*
AU  - Pinkenburg, O.*
AU  - Eldin, H.S.*
AU  - Binder, K.*
AU  - Jacob, R.*
AU  - Walker, A.
AU  - Stecher, B.*
AU  - Basic, M.*
AU  - Luu, M.*
AU  - Mahdavi, R.*
AU  - Heintz-Buschart, A.*
AU  - Visekruna, A.*
AU  - Steinhoff, U.*
C1  - 60369
C2  - 49391
CY  - 530 Walnut Street, Ste 850, Philadelphia, Pa 19106 Usa
SP  - 1-17
TI  - Dietary cellulose induces anti-inflammatory immunity and transcriptional programs via maturation of the intestinal microbiota.
JO  - Gut Microbes
VL  - 12
IS  - 1
PB  - Taylor & Francis Inc
PY  - 2020
SN  - 1949-0976
ER  -