Effect of oral multispecies probiotic on wound healing, periodontitis and quality of life on patients with diabetes.

OBJECTIVE: Hard-to-heal (chronic) wounds are common in patients with diabetes and are associated with a decrease in quality of life (QoL). Pathogenic bacteria often colonise hard-to-heal wounds and hinder the healing process which poses a high risk for (systemic) infections. In this study, we aim to prove that probiotics are capable of displacing human pathogenic bacteria, ameliorating inflammation and positively influencing the microenvironment/microbiome of skin and mucosa. METHOD: In this pilot study, patients with diabetes and hard-to-heal wounds with a duration of 2-120 months received an oral multispecies probiotic daily for six months. Changes in oral, stool and wound microbiome were investigated, and the effects of the probiotic intervention on wound healing, periodontitis and wound-specific quality of life (Wound-QOL-17) were analysed throughout the course of this clinical study. RESULTS: In total, seven of the 20 patients included were unable to complete the study. After six months of oral probiotic intake supplementation in five out of the remaining 13 patients, the wounds had healed completely. Most patients reported an improvement in wound-specific QoL, with particular positive effects on pain and mobility. Microbiome analysis revealed a reduction in Staphylococcus aureus and Pseudomonas aeruginosa, and Staphylococcus epidermis in healed wounds. CONCLUSION: This findings of this study provide evidence for the beneficial effects of the oral application of a multispecies probiotic over six months in patients with diabetes and hard-to-heal wounds on wound closure, wound microbial pattern, QoL, and on dental health. A randomised, placebo-controlled, double-blinded clinical trial is required to verify the results.

Oral microbiota of patients with phenylketonuria: A nation-based cross-sectional study.

AIM: The oral microenvironment contributes to microbial composition and immune equilibrium. It is considered to be influenced by dietary habits. Phenylketonuria (PKU) patients, who follow a lifelong low-protein diet, exhibit higher prevalence of oral diseases such as periodontitis, offering a suitable model to explore the interplay between diet, oral microbiota and oral health. MATERIALS AND METHODS: We conducted 16S rDNA sequencing on saliva and subgingival plaque from 109 PKU patients (ages 6-68 years) and 114 age-matched controls and correlated oral microbial composition and dental health. RESULTS: PKU patients exhibited worse dental health, reduced oral microbial diversity and a difference in the abundance of specific taxa, especially Actinobacteriota species, compared to controls. PKU patients with poor periodontal health exhibited higher alpha diversity than the orally healthy ones, marked by high abundance of the genus Tannerella. Notably, the observed taxonomic differences in PKU patients with normal indices of decayed/missing/filled teeth, plaque control record, gingival bleeding index and periodontal screening and recording index generally differed from microbial signatures of periodontitis. CONCLUSIONS: PKU patients' reduced microbial diversity may be due to their diet's metabolic challenges disrupting microbial and immune balance, thus increasing oral inflammation. Higher alpha diversity in PKU patients with oral inflammation is likely related to expanded microbial niches.

Investigating the metabolite signature of an altered oral microbiota as a discriminant factor for multiple sclerosis: a pilot study.

In multiple sclerosis (MS), alterations of the gut microbiota lead to inflammation. However, the role of other microbiomes in the body in MS has not been fully elucidated. In a pilot case-controlled study, we carried out simultaneous characterization of faecal and oral microbiota and conducted an in-depth analysis of bacterial alterations associated with MS. Using 16S rRNA sequencing and metabolic inference tools, we compared the oral/faecal microbiota and bacterial metabolism pathways in French MS patients (n = 14) and healthy volunteers (HV, n = 21). A classification model based on metabolite flux balance was established and validated in an independent German cohort (MS n = 12, HV n = 38). Our analysis revealed decreases in diversity indices and oral/faecal compartmentalization, the depletion of commensal bacteria (Aggregatibacter and Streptococcus in saliva and Coprobacter and Roseburia in faeces) and enrichment of inflammation-associated bacteria in MS patients (Leptotrichia and Fusobacterium in saliva and Enterobacteriaceae and Actinomyces in faeces). Several microbial pathways were also altered (the polyamine pathway and remodelling of bacterial surface antigens and energetic metabolism) while flux balance analysis revealed associated alterations in metabolite production in MS (nitrogen and nucleoside). Based on this analysis, we identified a specific oral metabolite signature in MS patients, that could discriminate MS patients from HV and rheumatoid arthritis patients. This signature allowed us to create and validate a discrimination model on an independent cohort, which reached a specificity of 92%. Overall, the oral and faecal microbiomes were altered in MS patients. This pilot study highlights the need to study the oral microbiota and oral health implications in patients with autoimmune diseases on a larger scale and suggests that knowledge of the salivary microbiome could help guide the identification of new pathogenic mechanisms associated with the microbiota in MS patients.

Assessment of the Inflammatory Effects of Gut Microbiota from Human Twins Discordant for Ulcerative Colitis on Germ-free Mice.

Disturbances in gut microbiota are prevalent in inflammatory bowel disease (IBD), which includes ulcerative colitis (UC). However, whether these disturbances contribute to development of the disease or are a result of the disease is unclear. In pairs of human twins discordant for IBD, the healthy twin has a higher risk of developing IBD and a gut microbiota that is more similar to that of IBD patients as compared with healthy individuals. Furthermore, appropriate medical treatment may mitigate these disturbances. To study the correlation between microbiota and IBD, we transferred stool samples from a discordant human twin pair: one twin being healthy and the other receiving treatment for UC. The stool samples were transferred from the disease-discordant twins to germ-free pregnant dams. Colitis was induced in the offspring using dextran sodium sulfate. As compared with offspring born to mice dams inoculated with stool from the healthy cotwin, offspring born to dams inoculated with stool from the UC-afflicted twin had a lower disease activity index, less gut inflammation, and a microbiota characterized by higher α diversity and a more antiinflammatory profile that included the presence and higher abundance of antiinflammatory species such as Akkermansia spp., Bacteroides spp., and Parabacteroides spp. These findings suggest that the microbiota from the healthy twin may have had greater inflammatory properties than did that of the twin undergoing UC treatment.

The archaeome in metaorganism research, with a focus on marine models and their bacteria-archaea interactions.

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.

Disease- and stage-specific alterations of the oral and fecal microbiota in Alzheimer's disease.

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.

The gut microbiome modulates associations between adherence to a Mediterranean-style diet, abdominal adiposity, and C-reactive protein in population-level analysis.

BACKGROUND: Adherence to a Mediterranean-style dietary pattern is likely to have variable effects on body composition, but the impact of gut microbiome on this relationship is unknown. OBJECTIVES: To examine the potential mediating effect of the gut microbiome on the associations between Alternate Mediterranean Diet (aMed) scores, abdominal adiposity, and inflammation in population-level analysis. DESIGN: In a community-based sample aged 25 to 83 y (n = 620; 41% female) from Northern Germany, we assessed the role of the gut microbiome, sequenced from 16S rRNA genes, on the associations between aMed scores, estimated using validated food-frequency questionnaires, magnetic resonance imaging-determined visceral (VAT) and subcutaneous (SAT) adipose tissue and C-reactive protein (CRP). RESULTS: Higher aMed scores were associated with lower SAT (-0.86 L (95% CI: -1.56, -0.17), P = 0.01), VAT (-0.65 L (95% CI: -1.03,-0.27), P = 0.01) and CRP concentrations (-0.35 mg/L; ß: -20.1% (95% CI: 35.5, -1.09), P = 0.04) in the highest versus lowest tertile after multivariate adjustment. Of the taxa significantly associated with aMed scores, higher abundance of Porphyromonadaceae mediated 11.6%, 9.3%, and 8.7% of the associations with lower SAT, VAT, and CRP, respectively. Conversely, a lower abundance of Peptostreptococcaceae mediated 13.1% and 18.2% of the association with SAT and CRP levels. Of the individual components of the aMed score, moderate alcohol intake was associated with lower VAT (-0.2 (95% CI: -0.4, -0.1), P =0.01) with a higher abundance of Oxalobacteraceae and lower abundance of Burkholderiaceae explaining 8.3% and 9.6% of this association, respectively. CONCLUSION: These novel data suggest that abundance of specific taxa in the Porphyromonadaceae and Peptostreptococcaceae families may contribute to the association between aMed scores, lower abdominal adipose tissue, and inflammation.

Antibiotic prophylaxis and hospitalization of horses subjected to median laparotomy: gut microbiota trajectories and abundance increase of Escherichia.

Introduction: Horse clinics are hotspots for the accumulation and spread of clinically relevant and zoonotic multidrug-resistant bacteria, including extended-spectrum ß-lactamase producing (ESBL) Enterobacterales. Although median laparotomy in cases of acute equine colic is a frequently performed surgical intervention, knowledge about the effects of peri-operative antibiotic prophylaxis (PAP) based on a combination of penicillin and gentamicin on the gut microbiota is limited. Methods: We collected fecal samples of horses from a non-hospitalized control group (CG) and from horses receiving either a pre-surgical single-shot (SSG) or a peri-operative 5-day (5DG) course of PAP. To assess differences between the two PAP regimens and the CG, all samples obtained at hospital admission (t0), on days three (t1) and 10 (t2) after surgery, were screened for ESBL-producing Enterobacterales and subjected to 16S rRNA V1-V2 gene sequencing. Results: We included 48 samples in the SSG (n = 16 horses), 45 in the 5DG (n = 15), and 20 in the CG (for t0 and t1, n = 10). Two samples of equine patients receiving antibiotic prophylaxis (6.5%) were positive for ESBL-producing Enterobacterales at t0, while this rate increased to 67% at t1 and decreased only slightly at t2 (61%). Shannon diversity index (SDI) was used to evaluate alpha-diversity changes, revealing there was no significant difference between horses suffering from acute colic (5DG, SDImean of 5.90, SSG, SDImean of 6.17) when compared to the CG (SDImean of 6.53) at t0. Alpha-diversity decreased significantly in both PAP groups at t1, while at t2 the onset of microbiome recovery was noticed. Although we did not identify a significant SDImean difference with respect to PAP duration, the community structure (beta-diversity) was considerably restricted in samples of the 5DG at t1, most likely due to the ongoing administration of antibiotics. An increased abundance of Enterobacteriaceae, especially Escherichia, was noted for both study groups at t1. Conclusion: Colic surgery and PAP drive the equine gut microbiome towards dysbiosis and reduced biodiversity that is accompanied by an increase of samples positive for ESBL-producing Enterobacterales. Further studies are needed to reveal important factors promoting the increase and residency of ESBL-producing Enterobacterales among hospitalized horses.

Effects of plant-based proteins and handling stress on intestinal mucus microbiota in rainbow trout.

Via 16S rRNA gene amplicon sequencing, this study explores whether the gut mucus microbiota of rainbow trout is affected by the interaction of a plant-protein-based diet and a daily handling stressor (chasing with a fishing net) across two genetic lines (A, B). Initial body weights of fish from lines A and B were 124.7 g and 147.2 g, respectively. Fish were fed 1.5% of body weight per day for 59 days either of two experimental diets, differing in their fish meal [fishmeal-based diet (F): 35%, plant-based diet (V): 7%] and plant-based protein content (diet F: 47%, diet V: 73%). No diet- or stress-related effect on fish performance was observed at the end of the trial. However, we found significantly increased observed ASVs in the intestinal mucus of fish fed diet F compared to diet V. No significant differences in Shannon diversity could be observed between treatments. The autochthonous microbiota in fish fed with diet V was dominated by representatives of the genera Mycoplasma, Cetobacterium, and Ruminococcaceae, whereas Enterobacteriaceae and Photobacterium were significantly associated with diet F. The mucus bacteria in both genetic lines were significantly separated by diet, but neither by stress nor an interaction, as obtained via PERMANOVA. However, pairwise comparisons revealed that the diet effect was only significant in stressed fish. Therefore, our findings indicate that the mucus-associated microbiota is primarily modulated by the protein source, but this modulation is mediated by the stress status of the fish.

Pesticides and the Microbiome-Gut-Brain Axis: Convergent Pathways in the Pathogenesis of Parkinson's Disease.

The increasing global burden of Parkinson's disease (PD), termed the PD pandemic, is exceeding expectations related purely to population aging and is likely driven in part by lifestyle changes and environmental factors. Pesticides are well recognized risk factors for PD, supported by both epidemiological and experimental evidence, with multiple detrimental effects beyond dopaminergic neuron damage alone. The microbiome-gut-brain axis has gained much attention in recent years and is considered to be a significant contributor and driver of PD pathogenesis. In this narrative review, we first focus on how both pesticides and the microbiome may influence PD initiation and progression independently, describing pesticide-related central and peripheral neurotoxicity and microbiome-related local and systemic effects due to dysbiosis and microbial metabolites. We then depict the bidirectional interplay between pesticides and the microbiome in the context of PD, synthesizing current knowledge about pesticide-induced dysbiosis, microbiome-mediated alterations in pesticide availability, metabolism and toxicity, and complex systemic pesticide-microbiome-host interactions related to inflammatory and metabolic pathways, insulin resistance and other mechanisms. An overview of the unknowns follows, and the role of pesticide-microbiome interactions in the proposed body-/brain-first phenotypes of PD, the complexity of environmental exposures and gene-environment interactions is discussed. The final part deals with possible further steps for translation, consisting of recommendations on future pesticide use and research as well as an outline of promising preventive/therapeutic approaches targeted on strengthening or restoring a healthy gut microbiome, closing with a summary of current gaps and future perspectives in the field.

Selection of aquatic microbiota exposed to the herbicides flufenacet and metazachlor.

Herbicides are important, ubiquitous environmental contaminants, but little is known about their interaction with bacterial aquatic communities. Here, we sampled a protected natural freshwater habitat and characterised its microbiome in interaction with herbicides. We evolved the freshwater microbiomes in a microcosm assay of exposure (28 days) to flufenacet and metazachlor at environmental concentrations of 0.5, 5 and 50 µg L-1 . Inhibitory effects of herbicides were exemplarily assessed in cultured bacteria from the same pond (Pseudomonas alcaligenes, Paenibacillus amylolyticus and Microbacterium hominis). Findings were compared to long-term concentrations as provided by local authorities. Here, environmental concentrations reached up to 11 µg L-1 (flufenacet) and 76 µg L-1 (metazachlor). Bacteria were inhibited at minimum inhibitory concentrations far above these values; however, concentrations of 50 µg L-1 of flufenacet resulted in measurable growth impairment. While most herbicide-exposed microcosm assays did not differ from controls, Acidobacteria were selected at high environmental concentrations of herbicides. Alpha-diversity (e.g., taxonomic richness on phylum level) was reduced when aquatic microbiomes were exposed to 50 µg metazachlor or flufenacet. One environmental strain of P. alcaligenes showed resistance to high concentrations of flufenacet (50 g L-1 ). In total, this study reveals that ecologic imbalance due to herbicide use significantly impacts aquatic microbiomes.

Amino acid auxotrophies in human gut bacteria are linked to higher microbiome diversity and long-term stability.

Amino acid auxotrophies are prevalent among bacteria. They can govern ecological dynamics in microbial communities and indicate metabolic cross-feeding interactions among coexisting genotypes. Despite the ecological importance of auxotrophies, their distribution and impact on the diversity and function of the human gut microbiome remain poorly understood. This study performed the first systematic analysis of the distribution of amino acid auxotrophies in the human gut microbiome using a combined metabolomic, metagenomic, and metabolic modeling approach. Results showed that amino acid auxotrophies are ubiquitous in the colon microbiome, with tryptophan auxotrophy being the most common. Auxotrophy frequencies were higher for those amino acids that are also essential to the human host. Moreover, a higher overall abundance of auxotrophies was associated with greater microbiome diversity and stability, and the distribution of auxotrophs was found to be related to the human host's metabolome, including trimethylamine oxide, small aromatic acids, and secondary bile acids. Thus, our results suggest that amino acid auxotrophies are important factors contributing to microbiome ecology and host-microbiome metabolic interactions.

[Relationships between microbiome and neurodegeneration]. / Zusammenhänge zwischen Mikrobiom und Neurodegeneration.

BACKGROUND: Neurodegenerative diseases are often associated with changes in the (gut) microbiome. OBJECTIVE: Based on studies in Parkinson's disease (PD) and Alzheimer's disease (AD), an overview of the current evidence of microbial changes and their possible role in the development of these diseases is given. METHODS: Analysis, summary, and evaluation of the current literature on (gut) microbiome and neurodegeneration. RESULTS: Numerous studies have shown dysbiotic changes in the gut microbiome of PD and AD patients compared to healthy individuals, some of which might occur even in the prodromal phase. Specifically, these patients show a reduction in bacteria involved in the synthesis of short-chain fatty acids. These microbial alterations have been associated with systemic inflammation and a compromised integrity of the intestinal barrier and blood-brain barrier. Bacterial molecules such as lipopolysaccharides may play an important role in these changes. Additionally, the bacterial protein curli, found on the surface of e.g., Escherichia coli, has been shown in vitro and in animal models to promote the misfolding of α-synuclein, thus suggesting a crucial pathomechanism. Moreover, certain oral bacteria appear to be more prevalent in AD patients and may contribute to the pathogenesis of AD. CONCLUSION: Neurodegenerative diseases are associated with dysbiosis of the (gut) microbiome, which can have diverse systemic effects; however, it remains unclear whether this dysbiosis is a cause or a consequence of the diseases. Further investigation of this (prodromal) microbial imbalance could reveal new approaches for targeted therapeutic manipulation of the microbiome to modify and prevent these diseases.

Pilot study on nasal microbiota dynamics and MRSA carriage of a pig cohort housed on straw bedding.

Methicillin-resistant Staphylococcus aureus (MRSA) can be transmitted between pigs and humans on farms. Hence, the reduction of MRSA carriage in pigs could decrease the risk of zoonotic transmission. Recently, straw bedding has been found to significantly reduce MRSA carriage in pigs. The mechanisms behind this effect remain unclear but changes in the nasal microbiome may play a role. In this exploratory study, the nasal microbiota of pigs kept on straw was examined using V1/V2 16S rRNA gene sequencing. Nasal swabs were collected from 13 pigs at six different time points during the course of a full fattening cycle resulting in 74 porcine samples. In addition, straw samples were collected at each time point. Eleven out of 13 pigs were MRSA positive at housing-in. We found a strong temporal pattern in the microbial communities. Both microbial diversity and abundance of Staphylococcus species peaked in week 5 after introduction to the straw stable decreased in week 10, when all pigs turned MRSA-negative, and increased again toward the end of the fattening period. These findings show that the introduction of pigs into a new environment has a huge impact on their nasal microbiota, which might lead to unfavorable conditions for MRSA. Moreover, other Staphylococcus species may play a role in eliminating MRSA carriage. We designed a follow-up study including two different husbandry systems to further assess these effects.

Association of the human gut microbiota with vascular stiffness.

Gut microbiota metabolites have been mechanistically linked to inflammatory pathway activation and atherosclerosis, which are major causes of vascular stiffness (VS). Aiming to investigate if the gut microbiome might be involved in VS development, we performed a cross-sectional study (n = 3,087), nested within the population-based European Prospective Investigations into Cancer and Nutrition (EPIC) Potsdam. We investigated the correlation of the gut microbiota (alpha diversity and taxa abundance) with 3 vascular stiffness measures: carotid-femoral (PWV), aortic augmentation index (AIX) and ankle-brachial index (ABI). Shannon index was not significantly associated with VS but the number of observed Amplicon Sequence Variants (ASV) was positively associated with PWV and AIX. We found a total of 19 ASVs significantly associated with at least one VS measure in multivariable-adjusted models. One ASV (classified as Sutterella wadsworthensis) was associated with 2 VS measures, AIX (- 0.11 ± 0.04) and PWV (-0.14 ± 0.03). Other examples of ASVs associated with VS were Collinsella aerofaciens, previously reported to be affected by diet and Bacteroides uniformis, commercially available as probiotics. In conclusion, our study suggests a potential role of individual components of the gut microbiota in the aetiology of VS.

A Gradient of Intestinal Inflammation in Primary Sclerosing Cholangitis.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a progressive liver disease associated with inflammatory bowel disease (IBD). The percentage of PSC patients diagnosed with concomitant IBD varies considerably between studies. This raises the question whether all PSC patients would show intestinal inflammation if screened thoroughly, even in the absence of symptoms. METHODS: To address this question, we collected intestinal biopsies of healthy controls (n = 34), PSC (n = 25), PSC-IBD (n = 41), and IBD (n = 51) patients in a cross-sectional study and carried out cytokine expression profiling, 16S sequencing, in-depth histology, and endoscopy scoring. RESULTS: We found that the vast majority of PSC patients even without clinically manifest IBD showed infiltration of immune cells and increased expression of IL17A and IFNG in intestinal biopsies. However, expression of IL10 and FOXP3 were likewise increased, which may explain why these PSC patients have intestinal inflammation only on a molecular level. This subclinical inflammation in PSC patients was focused in the distal colon, whereas PSC-IBD patients showed inflammation either at the distal colon or on the right side of the colon and the terminal ileum. Furthermore, we observed that PSC patients without IBD showed signs of dysbiosis and exhibited a distinct microbial profile compared with healthy controls. CONCLUSIONS: We found a gradient of intestinal inflammation in the vast majority of PSC patients even in the absence of IBD. Thus, further studies evaluating the effect of anti-inflammatory therapies in PSC patients and their impact on the emergence of clinically manifest IBD and colorectal cancer development are needed.

An Okinawan-Based Nordic Diet Leads to Profound Effects on Gut Microbiota and Plasma Metabolites Linked to Glucose and Lipid Metabolism.

Dietary interventions modify gut microbiota and clinical outcomes. Weight reduction and improved glucose and lipid homeostasis were observed after adopting an Okinawan-based Nordic diet (O-BN) in individuals with type 2 diabetes. The aim of the present study was to explore changes in metabolomics and gut microbiota during O-BN and correlate changes with clinical outcomes. A total of 30 patients (17 women), aged 57.5 ± 8.2 years, diabetes duration 10.4 ± 7.6 years, 90% over-weight, were included. Participants were provided an O-BN for 12 weeks. Before and after intervention, and 16 weeks afterwards, anthropometry and clinical data were estimated and questionnaires were collected, as well as samples of blood and stool. Plasma metabolomics were determined by gas- (GC-MS) or liquid- (LC-MS) chromatography-based mass spectrometry and fecal microbiota determination was based on 16S rRNA amplicons from regions V1-V2. During the intervention, weight (6.8%), waist circumference (6.1%), and levels of glucose, HbA1c, insulin, triglycerides, and cholesterol were decreased. Of 602 metabolites, 323 were changed for any or both periods; 199 (101 lipids) metabolites were decreased while 58 (43 lipids) metabolites were increased during the intervention. Changes in glucose homeostasis were linked to changes in, e.g., 1,5-anhydroglucitol, thyroxine, and chiro-inositol. Changes of microbe beta diversity correlated positively with food components and negatively with IL-18 (p = 0.045). Abundance differences at phylum and genus levels were found. Abundances of Actinobacteria, Bacteroidetes, Firmicutes, and Verrucomicrobia correlated with anthropometry, HbA1c, lipids, inflammation, and food. Changes in metabolites and microbiota were reversed after the intervention. The O-BN-induced changes in metabolomics and gut microbiota correspond to clinical outcomes of reduced weight and inflammation and improved glucose and lipid metabolism.

Investigating the Crime Scene-Molecular Signatures in Inflammatory Bowel Disease.

Inflammatory bowel diseases (IBD) are without cure and troublesome to manage because of the considerable diversity between patients and the lack of reliable biomarkers. Several studies have demonstrated that diet, gut microbiota, genetics and other patient factors are essential for disease occurrence and progression. Understanding the link between these factors is crucial for identifying molecular signatures that identify biomarkers to advance the management of IBD. Recent technological breakthroughs and data integration have fuelled the intensity of this research. This research demonstrates that the effect of diet depends on patient factors and gut microbial activity. It also identifies a range of potential biomarkers for IBD management, including mucosa-derived cytokines, gasdermins and neutrophil extracellular traps, all of which need further evaluation before clinical translation. This review provides an update on cutting-edge research in IBD that aims to improve disease management and patient quality of life.

Sterile Fecal Filtrate From A Healthy Donor Improves Microbial Diversity In Patients With Hepatic Encephalopathy.

BACKGROUND AND AIMS: Hepatic encephalopathy (HE) remains one of the most debilitating complications of liver cirrhosis. Changes in gut microbiome composition have been linked to liver diseases and its complications including HE. Recent randomized controlled trials showed fecal microbiota transplantation to be safe and effective in HE treatment, however transferring unidentified live bacteria could cause various complications, including infections, especially in immunocompromised patients. This study aimed to evaluate the safety and efficacy of sterile fecal filtrate transfer (SFFT) for the modulation of the intestinal microbiome of patients with cirrhosis and HE. METHODS: A custom-made air pressure filtration device was used for the sterile fecal filtrate preparation. Seven patients received SFFT from the same healthy donor. Patients were monitored at least 30 days after the procedure. Cognition tests, blood and stool sampling were performed to assess the safety and efficacy of SFFT on HE, liver function, and stool microbiome composition on follow-up days 7 and 30. RESULTS: SFFT was well tolerated and resulted in fluctuations in the microbial composition of study participants: α-diversity increased in 4/7 of the patients, without robust engraftment of donors' microbial composition as assessed by ß-diversity analysis. No significant effect on cognition tests or liver function was noted after the procedure. One death occurred three months after the procedure, however, it was not related to the SFFT. CONCLUSIONS: Despite the effect on the gut microbiome, we did not observe robust improvement in patients' liver function or HE cognition tests after the procedure.

The microbiota knows: handling-stress and diet transform the microbial landscape in the gut content of rainbow trout in RAS.

BACKGROUND: The aim of the present study was to characterize the effects of handling stress on the microbiota in the intestinal gut contents of rainbow trout (Oncorhynchus mykiss) fed a plant-based diet from two different breeding lines (initial body weights: A: 124.69 g, B: 147.24 g). Diets were formulated in accordance with commercial trout diets differing in their respective protein sources: fishmeal (35% in fishmeal-based diet F, 7% in plant protein-based diet V) and plant-based proteins (47% in diet F, 73% in diet V). Experimental diets were provided for 59 days to all female trout in two separate recirculating aquaculture systems (RASs; mean temperature: A: 15.17 °C ± 0.44, B: 15.42 °C ± 0.38). Half of the fish in each RAS were chased with a fishing net twice per day to induce long-term stress (Group 1), while the other half were not exposed to stress (Group 0). RESULTS: No differences in performance parameters were found between the treatment groups. By using 16S rRNA amplicon sequencing of the hypervariable region V3/V4, we examined the microbial community in the whole intestinal content of fish at the end of the trial. We discovered no significant differences in alpha diversity induced by diet or stress within either genetic trout line. However, the microbial composition was significantly driven by the interaction of stress and diet in trout line A. Otherwise, in trout line B, the main factor was stress. The communities of both breeding lines were predominantly colonized by bacteria from the phyla Fusobacteriota, Firmicutes, Proteobacteria, Actinobacteriota, and Bacteroidota. The most varying and abundant taxa were Firmicutes and Fusobacteriota, whereas at the genus level, Cetobacterium and Mycoplasma were key components in terms of adaptation. In trout line A, Cetobacterium abundance was affected by factor stress, and in trout line B, it was affected by the factor diet. CONCLUSION: We conclude that microbial gut composition, but neither microbial diversity nor fish performance, is highly influenced by stress handling, which also interacts with dietary protein sources. This influence varies between different genetic trout lines and depends on the fish's life history.