Association of metformin administration with gut microbiome dysbiosis in healthy volunteers

BackgroundLung cancer (LC) is one of the most aggressive, prevalent and fatal malignancies. Gut microbes and their associated metabolites are thought to cause and modulate LC development, albeit influenced by the host genetic make-up and environment. Herein, we identified and classified gut microbiota and serum metabolites associated with LC.MethodsStool samples were collected from 41 LC patients and 40 healthy volunteers. The gut microbiota was analyzed using 16S rRNA gene sequencing. Serum samples were collected from the same LC patients (n=30) and healthy volunteers (n=30) and serum metabolites were analyzed using liquid chromatography-mass spectrometry (LC-MS). Microbiome and metabolome data were analyzed separately and integrated for combined analysis using various bioinformatics methods.ResultsSerum metabolomics uncovered 870 metabolites regulated in 76 metabolic pathways in both groups. Microbial diversity analyses identified 15967 operational taxonomic units (OTUs) in groups. Of these, the abundance of 232 OTUs was significantly different between HC and LC groups. Also, serum levels of glycerophospholipids (LysoPE 18:3, LysoPC 14:0, LysoPC 18:3), Imidazopyrimidines (Hypoxanthine), AcylGlcADG 66:18; AcylGlcADG (22:6/22:6/22:6) and Acylcarnitine 11:0 were substantially different between HC and LC groups. Combined analysis correlated LC-associated microbes with metabolites, such as Erysipelotrichaceae_UCG_003, Clostridium and Synergistes with glycerophospholipids.ConclusionsThere is an intricate relationship between gut microbiome and levels of several metabolites such as glycerophospholipids and imidazopyrimidines. Microbial-associated metabolites are potential diagnostic biomarkers and therapeutic targets for LC.

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Disruption of the pro-inflammatory, anti-inflammatory cytokines and tight junction proteins expression, associated with changes of the composition of the gut microbiota in patients with irritable bowel syndrome

PLoS ONE ◽

10.1371/journal.pone.0252930 ◽

2021 ◽

Vol 16 (6) ◽

pp. e0252930

Author(s):

V. Ivashkin ◽

Y. Poluektov ◽

E. Kogan ◽

O. Shifrin ◽

A. Sheptulin ◽

...

Keyword(s):

Tight Junction ◽

Healthy Volunteers ◽

Gut Microbiome ◽

Low Grade ◽

Tight Junction Proteins ◽

Microbiome Composition ◽

Tnf Α ◽

Irritable Bowel ◽

Low Grade Inflammation ◽

Junction Proteins

Background Irritable bowel syndrome (IBS) is a pathologic condition characterized by changes in gut microbiome composition, low-grade inflammation, and disruption of intestinal wall permeability. The interaction between the gut microbiome and the disease manifestation remains unclear. The changing of tight junction proteins and cytokines expression throughout the gastrointestinal tract in IBS patients has not been studied yet. Aim of the study To assess the changes of gut microbiome composition, tight junction proteins, and cytokines expression of intestinal mucosa from the duodenum to the distal part of the colon in IBS patients and healthy volunteers. Methods In 31 IBS patients (16 patients with IBS-D; 15 patients with IBS-C) and 10 healthy volunteers the expression of CLD-2, CLD-3, CLD-5, IL-2, IL-10, and TNF-α in mucosal biopsy specimens was determined by morphological and immune-histochemical methods. The qualitative and quantitative composition of the intestinal microbiota was assessed based on 16S rRNA gene sequencing in both groups of patients. Results The expression of IL-2 and TNF-α was significantly increased in IBS patients compared with the controls (p<0.001), with a gradual increase from the duodenum to the sigmoid colon. The expression of IL-10, CLD-3, and CLD-5 in mucosal biopsy specimens of these patients was lower than in the control group (p<0.001). Increased ratios of Bacteroidetes and decreased ratios of Firmicutes were noted in IBS patients compared to healthy volunteers (p<0.05). Conclusion IBS patients have impaired gut permeability and persisting low-grade inflammation throughout the gastrointestinal tract. Changes in the gut microbiota may support or exacerbate these changes.

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A single alcohol binge impacts on neutrophil function without changes in gut barrier function and gut microbiome composition in healthy volunteers

PLoS ONE ◽

10.1371/journal.pone.0211703 ◽

2019 ◽

Vol 14 (2) ◽

pp. e0211703 ◽

Cited By ~ 3

Author(s):

Vanessa Stadlbauer ◽

Angela Horvath ◽

Irina Komarova ◽

Bianca Schmerboeck ◽

Nicole Feldbacher ◽

...

Keyword(s):

Healthy Volunteers ◽

Gut Microbiome ◽

Barrier Function ◽

Neutrophil Function ◽

Gut Barrier ◽

Microbiome Composition ◽

Gut Barrier Function

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Effects of Inulin Consumption on the Gut Microbiome During Fasting: A Pilot Study in Healthy Volunteers

Current Developments in Nutrition ◽

10.1093/cdn/nzab054_041 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 1186-1186

Author(s):

Kerstin Thriene ◽

Lena Amend ◽

Till Strowig ◽

Karin Michels

Keyword(s):

Healthy Volunteers ◽

Caloric Restriction ◽

Gut Microbiome ◽

Intervention Study ◽

Metabolic Diseases ◽

Alpha Diversity ◽

Calorie Intake ◽

Microbial Composition ◽

Fasting Period ◽

Pilot Intervention

Abstract Objectives Caloric restriction has been associated with beneficial effects on metabolic diseases such as type 2 diabetes, cardiovascular diseases, and cancer but the mechanisms are diverse and not fully understood. Interactions between the human host and its gut microbiota might play a crucial role in this context, but these have not yet been analysed in detail. Therefore, we conducted a pilot intervention study to investigate how the microbial community in the human gut adapts to caloric restriction. Additionally, we investigated whether the compliance improved if the participants during fasting consumed prebiotics, which are supposed to reduce sensations of hunger while not providing calories through digestion in the small intestine. Methods We recruited six healthy volunteers (age: 20–50 years, BMI: 20–25 kg/m2) for a pilot intervention study using a randomized crossover design. The study consisted of two sequential fasting periods of which one included additional prebiotics. Participants were fasting for three consecutive days consuming a total of 300 kcal daily provided by vegetable juices, framed by two days with a total daily calorie intake of 800 kcal, respectively. During one of the fasting periods, participants consumed additionally 24 g of inulin daily. Stool samples were collected for the analysis of the microbial composition by 16S rRNA sequencing. Results We observed no clear change in alpha diversity during the period of caloric reduction. However, quantitative changes in the composition of the microbiome was visible in mainly all participants. Additional intake of the prebiotic inulin did not influence compliance for the fasting intervention. However, we observed a clear reduction in alpha diversity in the gut microbiome after inulin ingestion during the fasting period. Conclusions Caloric restriction appears to have no significant influence on the gut microbiome itself but inulin consumption during fasting seems to selectively promote the growth of some bacterial families leading to an overall decrease of alpha diversity in the gut microbiome. Further studies with a larger sample size are warranted to verify our observations. Funding Sources Institutional budget, no external funding.

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Hypertension- and glycaemia-lowering effects of a grape-pomace-derived seasoning in patients and healthy volunteers. Interplay with the gut microbiome

Food & Function ◽

10.1039/d1fo03942c ◽

2022 ◽

Author(s):

Diego Taladrid ◽

Miguel de Celis ◽

Ignacio Belda ◽

Begoña Bartolome ◽

M. Victoria Moreno-Arribas

Keyword(s):

Healthy Volunteers ◽

Gut Microbiome ◽

Dietary Fibre ◽

Grape Pomace ◽

Low Salt

Grape pomace (GP) is a winery by-product rich in polyphenols and dietary fibre. Recently, GP-derived seasonings have emerged as promising additives in food, specially recommended for low-salt diets. The hypothesis...

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The Gut Microbiome and Resistome of Healthy Volunteers are Restructured After Short Courses of Antibiotics

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2020.476 ◽

2020 ◽

Vol 41 (S1) ◽

pp. s5-s6

Author(s):

Winston Anthony ◽

Kimberley Sukhum ◽

Candice Cass ◽

Kimberly Reske ◽

Sondra Seiler ◽

...

Keyword(s):

Healthy Volunteers ◽

Relative Abundance ◽

Gut Microbiome ◽

Community Diversity ◽

Metabolic Profiles ◽

Innate Resistance ◽

Starting Point ◽

Stool Samples ◽

Stool Specimens ◽

Short Courses

Background: Antimicrobial exposure is a significant risk factor for the development of antibiotic-resistant organisms (ARO); however, the depth and duration of this impact is not well described. The study goal is to define impact of antibiotics on the gut microbiome of healthy volunteers (HVs). Methods: HVs were randomized to receive either 5 days of levofloxacin (LVX), azithromycin (AZM), cefpodoxime (CPD), or AZM + CPD (Fig. 1). Stool samples were collected at 15 time points per patient before, during, and after antibiotics. Remnant stool samples from the microbiology laboratory were collected from patients admitted to the medical intensive care unit (MICU) as a comparison of the microbiome in a critically ill state. DNA was extracted from samples and was submitted for shotgun sequencing. Relative abundance, resistome, and metabolic pathway abundance of bacterial taxa were determined and statistical analysis conducted in R software. Results: In total, 289 stool specimens from 20 HVs, and 26 remnant stool specimens were obtained from patients admitted from the MICU (Fig. 1). Community diversity and richness decreased in the first week post-ABX for all HVs (P < .01). Linear discriminant analysis identified Bacteroides and Clostridium as taxonomic groups enriched after CPD, while AZM and LVX produced a relative abundance increase in diverse Firmicutes spp. Longitudinal tracking confirmed that after all antibiotics except LVX, HV microbiomes lost species diversity and shifted toward a state similar to that observed in MICU patients (Fig. 2). The gut microbiome of most HVs exhibited resiliency and returned to a higher diversity level similar to their starting point; however, 10% of HVs did not. Moreover, antibiotic-specific increases in resistance markers reveal innate resistance to β-lactams and macrolides within the gut microbiome of the HVs. Finally, HV microbiomes, which shifted toward a MICU-like taxonomic state, also clustered with microbial metabolic profiles from MICU patients.The HV microbial metabolic profiles were significantly enriched for important biosynthesis pathways producing chorismate and polysaccharides. MICU patient gut microbiomes were enriched for fatty acid regulation and quinolone biosynthesis, and for many degradation pathways important for different aspects of antibiotic resistance such as membrane integrity, alternative respiration, and antibiotic inactivation. Conclusions: Short courses of antibiotics can cause acute and chronic microbiome disruptions in HVs, as evidenced by decreased microbiome diversity and increases in specific innate resistance elements. These data support the need for antimicrobial stewardship to support rationale antibiotic use to prevent gut microbiome disruptions.Funding: CDC BAA 200-2016-91962Disclosures: None

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Longitudinal profiling of the gut microbiome in patients with psoriatic arthritis and ankylosing spondylitis: a multicentre, prospective, observational study

BMC Rheumatology ◽

10.1186/s41927-020-00155-2 ◽

2020 ◽

Vol 4 (1) ◽

Author(s):

Jesus Miguens Blanco ◽

Federica Borghese ◽

Neil McHugh ◽

Peter Kelleher ◽

Raj Sengupta ◽

...

Keyword(s):

Psoriatic Arthritis ◽

Ankylosing Spondylitis ◽

Observational Study ◽

Healthy Volunteers ◽

Gut Microbiome ◽

Prospective Observational Study ◽

Previous History ◽

Gastrointestinal Surgery ◽

Control Group ◽

Food Diary

Abstract Background Psoriasis is a chronic inflammatory disease of the skin affecting 2–3% of UK population. 30% of people affected by psoriasis will develop a distinct form of arthritis within 10 years of the skin condition onset. Although the pathogenesis of psoriatic arthritis is still unknown, there is a genetic predisposition triggered by environmental factors. Limited but convincing evidence link the gut microbiome to psoriatic arthritis. The Microbiome in Psoriatic ARThritis (Mi-PART) study propose is to characterise the microbiome-metabolic interface in patients affected by psoriatic arthritis to deepen our understanding of the pathogenesis of the disease. Methods This is a multicentre, prospective, observational study. Psoriatic arthritis (n = 65) and ankylosing spondylitis (n = 30) patients will be recruited in addition to a control group of healthy volunteers (n = 30). Patients eligibility will be evaluated against the Criteria for Psoriatic Arthritis (CASPAR), the Bath Ankylosing Spondylitis Activity Index (BASDAI) and the healthy volunteers who fulfil study inclusion and exclusion criteria. Information regarding their medical and medication history, demographics, diet and lifestyle will be collected. All the participants in the study will be asked to complete a 7-day food diary, to provide stool samples and to complete quality of life questionnaires. Routine clinical laboratory tests will be performed on blood and urine samples. Patients and healthy volunteers with gastrointestinal symptoms, previous history of cancer, gastrointestinal surgery in the previous 6 months or alcohol abuse will be excluded from the study. Discussion The aim of this trial is to characterise the microbiome of psoriatic arthritis patients and to compare it with microbiome of healthy volunteers and of patient with ankylosing spondylitis in order to define if different rheumatologic conditions are associated with characteristic microbiome profiles. Investigating the role of the microbiome in the development of psoriatic arthritis could deepen our understanding of the pathogenesis of the disease and potentially open the way to new therapies.

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