2579. Impact on the Gut Microbiota of the Prolonged Antimicrobial Therapy in Patients with Bone and Joint Infection (BJI): Results From the OSIRIS Prospective Study in France

Abstract Background There is growing interest about the deleterious impact of antibiotics on loss of gut symbiosis, called dysbiosis. As patients with BJI require antibiotics usually during 6 to 12 weeks, it is of interest to determine whether dysbiosis is frequent in this population, and if it could potentially reversible or not. Methods Multicentric prospective cohort study in France (EudraCT 2016-003247-10) including patients with 3 categories of BJI: native, osteosynthesis-related and prosthetic joint infection (PJI). At the time of suspicion (V1), at the end of therapy (V2) and then 2 weeks after stopping therapy (V3), blood and fecal samples were collected. Extracted DNA from stool was sequenced using shotgun metagenomic sequencing based on illumina library and Iseq instrumentation. Data run through a dedicated pipeline in order to produce microbiome indexes such as Sympson or Shannon diversities indexes. Gut microbiome and inflammation markers were analyzed including fecal neopterin, a maker of gut inflammation. Results Concerning the 62 patients included (mean age, 60 years; mean duration of antibiotics, 66 days), 27 had native, 14 had osteosynthesis and 21 had PJI. The most frequently prescribed drug was a fluoroquinolone, followed by a third-generation cephalosporin and vancomycin. Stools from 42 of them were analyzed as per protocol. Overall, the mean Shannon richness index decreased from 0.904 at V1 to 0.845 at V2; the Bray-Curtis index underlined the difference in microbiome reconstitution at V3 in comparison with V1. We report significant microbiome loss of diversity at V2, that was reversible at V3 in patients with native BJI and osteosynthesis-related BJI, but not in patients with PJI (figure). Fecal neopterin increased between V1 and V2 (mean 221.6 and 698.1 pmol/g of feces, respectively) and then decreased at V3 (422.5 pmol/g), and could be a potential surrogate marker of gut dysbiosis. Of note, patients with abnormal CRP at the end of antibiotics had high neopterin values, that raises the hypothesis that abnormal CRP at the end of antibiotics could be in relation with gut dysbiosis rather than uncured BJI. Conclusion The impact of antibiotics on the gut microbiota of patients with BJI seems to be significant, especially in patients with PJI who could be candidate for fecal microbiota transplantation. Disclosures All authors: No reported disclosures.

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Crosstalk between Gut and Brain in Alzheimer’s Disease: The Role of Gut Microbiota Modulation Strategies

Nutrients ◽

10.3390/nu13020690 ◽

2021 ◽

Vol 13 (2) ◽

pp. 690

Author(s):

Umair Shabbir ◽

Muhammad Sajid Arshad ◽

Aysha Sameen ◽

Deog-Hwan Oh

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Gut Microbiota ◽

Dietary Habits ◽

Inflammatory Responses ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Gut Dysbiosis ◽

Dynamic Population

The gut microbiota (GM) represents a diverse and dynamic population of microorganisms and about 100 trillion symbiotic microbial cells that dwell in the gastrointestinal tract. Studies suggest that the GM can influence the health of the host, and several factors can modify the GM composition, such as diet, drug intake, lifestyle, and geographical locations. Gut dysbiosis can affect brain immune homeostasis through the microbiota–gut–brain axis and can play a key role in the pathogenesis of neurodegenerative diseases, including dementia and Alzheimer’s disease (AD). The relationship between gut dysbiosis and AD is still elusive, but emerging evidence suggests that it can enhance the secretion of lipopolysaccharides and amyloids that may disturb intestinal permeability and the blood–brain barrier. In addition, it can promote the hallmarks of AD, such as oxidative stress, neuroinflammation, amyloid-beta formation, insulin resistance, and ultimately the causation of neural death. Poor dietary habits and aging, along with inflammatory responses due to dysbiosis, may contribute to the pathogenesis of AD. Thus, GM modulation through diet, probiotics, or fecal microbiota transplantation could represent potential therapeutics in AD. In this review, we discuss the role of GM dysbiosis in AD and potential therapeutic strategies to modulate GM in AD.

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Insights into the Impact of Microbiota in the Treatment of NAFLD/NASH and Its Potential as a Biomarker for Prognosis and Diagnosis

Biomedicines ◽

10.3390/biomedicines9020145 ◽

2021 ◽

Vol 9 (2) ◽

pp. 145

Author(s):

Julio Plaza-Díaz ◽

Patricio Solis-Urra ◽

Jerónimo Aragón-Vela ◽

Fernando Rodríguez-Rodríguez ◽

Jorge Olivares-Arancibia ◽

...

Keyword(s):

Gut Microbiota ◽

Fecal Microbiota Transplantation ◽

Liver Steatosis ◽

Intestinal Barrier ◽

Fecal Microbiota ◽

Current Treatment ◽

Immune Defense ◽

Alcoholic Fatty Liver ◽

The Impact

Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver illness associated with obesity and metabolic disorders, such as hypertension, dyslipidemia, or type 2 diabetes mellitus. A more severe type of NAFLD, non-alcoholic steatohepatitis (NASH), is considered an ongoing global health threat and dramatically increases the risks of cirrhosis, liver failure, and hepatocellular carcinoma. Several reports have demonstrated that liver steatosis is associated with the elevation of certain clinical and biochemical markers but with low predictive potential. In addition, current imaging methods are inaccurate and inadequate for quantification of liver steatosis and do not distinguish clearly between the microvesicular and the macrovesicular types. On the other hand, an unhealthy status usually presents an altered gut microbiota, associated with the loss of its functions. Indeed, NAFLD pathophysiology has been linked to lower microbial diversity and a weakened intestinal barrier, exposing the host to bacterial components and stimulating pathways of immune defense and inflammation via toll-like receptor signaling. Moreover, this activation of inflammation in hepatocytes induces progression from simple steatosis to NASH. In the present review, we aim to: (a) summarize studies on both human and animals addressed to determine the impact of alterations in gut microbiota in NASH; (b) evaluate the potential role of such alterations as biomarkers for prognosis and diagnosis of this disorder; and (c) discuss the involvement of microbiota in the current treatment for NAFLD/NASH (i.e., bariatric surgery, physical exercise and lifestyle, diet, probiotics and prebiotics, and fecal microbiota transplantation).

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Longitudinal Analyses Reveal That Aging-related Alterations in the Intestinal Environment Lead to Gut Dysbiosis With the Potential to Induce Obesity

10.21203/rs.3.rs-119480/v1 ◽

2020 ◽

Author(s):

Yumiko Nakanishi ◽

Ryouko Nozu ◽

Masami Ueno ◽

Kyoji Hioki ◽

Chiharu Ishii ◽

...

Keyword(s):

Gut Microbiota ◽

Middle Age ◽

Fecal Microbiota Transplantation ◽

Fold Increase ◽

Fecal Microbiota ◽

Whole Body ◽

Cellular Functions ◽

Intestinal Environment ◽

Gut Dysbiosis ◽

Specific Pathogen

Abstract Background: Aging is a progressive decline of cellular functions that ultimately affects whole-body homeostasis. Alterations in the gut microbiota associated with aging have been reported, however the molecular basis of the relationships between host aging and the gut microbiota is poorly understood.Result: By using longitudinal microbiome and metabolome characterization, we show that the aging-related alterations in the intestinal environment lead to gut dysbiosis with a potential to induce obesity in mice. In middle-age mice, we observed more than a 2-fold increase in fecal carbohydrates derived from dietary polysaccharides and a significant reduction of gut microbial diversity resembling the microbiota characteristic of obese mice. Consistently, fecal microbiota transplantation from middle-age specific pathogen-free (SPF) mice into young germ-free (GF) mice resulted in increased weight gain and impaired glucose tolerance.Conclusion: Our findings provide new insights into the relationships between host aging and gut dysbiosis and may contribute to the development of a possible solution to aging-related obesity.

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Time-restricted feeding induces Lactobacillus- and Akkermansia-specific functional changes in the rat fecal microbiota

npj Biofilms and Microbiomes ◽

10.1038/s41522-021-00256-x ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Antonio Palomba ◽

Alessandro Tanca ◽

Marcello Abbondio ◽

Rosangela Sau ◽

Monica Serra ◽

...

Keyword(s):

Gut Microbiota ◽

Protein Metabolism ◽

Fecal Microbiota ◽

Metagenomic Sequencing ◽

Restricted Feeding ◽

Dietary Regimen ◽

Functional Changes ◽

Host Health ◽

Key Factor ◽

The Impact

AbstractDiet is a key factor influencing gut microbiota (GM) composition and functions, which in turn affect host health. Among dietary regimens, time-restricted (TR) feeding has been associated to numerous health benefits. The impact of TR feeding on the GM composition has been mostly explored by means of metagenomic sequencing. To date, however, little is known about the modulation of GM functions by this dietary regimen. Here, we analyzed the effects of TR feeding on GM functions by evaluating protein expression changes in a rat model through a metaproteomic approach. We observed that TR feeding has a relevant impact on GM functions, specifically leading to an increased abundance of several enzymes involved in carbohydrate and protein metabolism and expressed by Lactobacillus spp. and Akkermansia muciniphila. Taken together, these results contribute to deepening our knowledge about the key relationship between diet, GM, and health.

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Cross-Talk Between Butyric Acid and Gut Microbiota in Ulcerative Colitis Following Fecal Microbiota Transplantation

Frontiers in Microbiology ◽

10.3389/fmicb.2021.658292 ◽

2021 ◽

Vol 12 ◽

Author(s):

Hao-Ming Xu ◽

Hong-Li Huang ◽

Jing Xu ◽

Jie He ◽

Chong Zhao ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiota ◽

Butyric Acid ◽

Fecal Microbiota Transplantation ◽

Short Chain Fatty Acids ◽

Fecal Microbiota ◽

16S Sequencing ◽

Α Diversity ◽

The Impact

Fecal microbiota transplantation (FMT) can inhibit the progression of ulcerative colitis (UC). However, how FMT modulates the gut microbiota and which biomarker is valuable for evaluating the efficacy of FMT have not been clarified. This study aimed to determine the changes in the gut microbiota and their relationship with butyric acid following FMT for UC. Fecal microbiota (FM) was isolated from healthy individuals or mice and transplanted into 12 UC patients or colitis mice induced by dextran sulfate sodium (DSS). Their clinical colitis severities were monitored. Their gut microbiota were analyzed by 16S sequencing and bioinformatics. The levels of fecal short-chain fatty acids (SCFAs) from five UC patients with recurrent symptoms after FMT and individual mice were quantified by liquid chromatography–mass spectrometry (LC–MS). The impact of butyric acid on the abundance and diversity of the gut microbiota was tested in vitro. The effect of the combination of butyric acid-producing bacterium and FMT on the clinical responses of 45 UC patients was retrospectively analyzed. Compared with that in the controls, the FMT significantly increased the abundance of butyric acid-producing bacteria and fecal butyric acid levels in UC patients. The FMT significantly increased the α-diversity, changed gut microbial structure, and elevated fecal butyric acid levels in colitis mice. Anaerobic culture with butyrate significantly increased the α-diversity of the gut microbiota from colitis mice and changed their structure. FMT combination with Clostridium butyricum-containing probiotics significantly prolonged the UC remission in the clinic. Therefore, fecal butyric acid level may be a biomarker for evaluating the efficacy of FMT for UC, and addition of butyrate-producing bacteria may prolong the therapeutic effect of FMT on UC by changing the gut microbiota.

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The Role of Gut Microbiota in Lung Cancer: From Carcinogenesis to Immunotherapy

Frontiers in Oncology ◽

10.3389/fonc.2021.720842 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xiangjun Liu ◽

Ye Cheng ◽

Dan Zang ◽

Min Zhang ◽

Xiuhua Li ◽

...

Keyword(s):

Lung Cancer ◽

Gut Microbiota ◽

Gut Microbiome ◽

Fecal Microbiota Transplantation ◽

Checkpoint Inhibitors ◽

Fecal Microbiota ◽

Immune Homeostasis ◽

Gut Dysbiosis ◽

Underlying Mechanisms ◽

And Function

The influence of microbiota on host health and disease has attracted adequate attention, and gut microbiota components and microbiota-derived metabolites affect host immune homeostasis locally and systematically. Some studies have found that gut dysbiosis, disturbance of the structure and function of the gut microbiome, disrupts pulmonary immune homeostasis, thus leading to increased disease susceptibility; the gut-lung axis is the primary cross-talk for this communication. Gut dysbiosis is involved in carcinogenesis and the progression of lung cancer through genotoxicity, systemic inflammation, and defective immunosurveillance. In addition, the gut microbiome harbors the potential to be a novel biomarker for predicting sensitivity and adverse reactions to immunotherapy in patients with lung cancer. Probiotics and fecal microbiota transplantation (FMT) can enhance the efficacy and depress the toxicity of immune checkpoint inhibitors by regulating the gut microbiota. Although current studies have found that gut microbiota closely participates in the development and immunotherapy of lung cancer, the mechanisms require further investigation. Therefore, this review aims to discuss the underlying mechanisms of gut microbiota influencing carcinogenesis and immunotherapy in lung cancer and to provide new strategies for governing gut microbiota to enhance the prevention and treatment of lung cancer.

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Fecal microbiota transplantation brings about bacterial strain displacement in patients with inflammatory bowel diseases

10.1101/439687 ◽

2018 ◽

Cited By ~ 1

Author(s):

Manli Zou ◽

Zhuye Jie ◽

Bota Cui ◽

Honggang Wang ◽

Qiang Feng ◽

...

Keyword(s):

Gut Microbiota ◽

Fecal Microbiota Transplantation ◽

Bacterial Colonization ◽

Fecal Microbiota ◽

Classification Model ◽

Metagenomic Data ◽

Metagenomic Sequencing ◽

Fecal Samples ◽

Inflammatory Bowel

ABSTRACTFecal microbiota transplantation (FMT), which is thought to have the potential to correct dysbiosis of gut microbiota, has recently been used to treat inflammatory bowel disease (IBD). To elucidate the extent and principles of microbiota engraftment in IBD patients after FMT treatment, we conducted an interventional prospective cohort study. The cohort included two categories of patients: (1) patients with moderate to severe Crohn’s disease (CD) (Harvey-Bradshaw Index ≥ 7, n = 11, and (2) patients with ulcerative colitis (UC) (Montreal classification, S2 and S3, n = 4). All patients were treated with a single FMT (via mid-gut, from healthy donors) and follow-up visits were performed at baseline, 3 days, one week, and one month after FMT (missing time points included). At each follow-up time point, fecal samples of the participants were collected along with their clinical metadata. For comparative analysis, 10 fecal samples from 10 healthy people were included to represent the diversity level of normal gut microbiota. Additionally, the metagenomic data of 25 fecal samples from 5 individuals with metabolic syndrome who underwent autologous FMT treatment were downloaded from a previous published paper to represent natural microbiota shifts during FMT. All fecal samples underwent shotgun metagenomic sequencing.We found that 3 days after FMT, 11 out of 15 recipients were in remission (3 out of 4 UC recipients; 8 out of 11 CD recipients). Generally, bacterial colonization was observed to be lower in CD recipients than in UC recipients at both species and strain levels. Furthermore, across species, different strains displayed disease-specific displacement advantages under two-disease status. Finally, most post-FMT species (> 80%) could be properly predicted (AUC > 85%) using a random forest classification model, with the gut microbiota composition and clinical parameters of pre-FMT recipients acting as the most contributive factors for prediction accuracy.

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Gastrointestinal disturbance and effect of fecal microbiota transplantation in discharged COVID-19 patients

10.21203/rs.3.rs-54135/v1 ◽

2020 ◽

Author(s):

Zhaoqun Deng ◽

Fengqiong Liu ◽

Shanliang Ye ◽

Xin Zhu ◽

Xuesong He ◽

...

Keyword(s):

B Cells ◽

Gut Microbiota ◽

Post Infection ◽

Fecal Microbiota Transplantation ◽

Gastrointestinal Symptoms ◽

Fecal Microbiota ◽

Psychological Disorder ◽

Community Diversity ◽

General Distribution ◽

Gut Dysbiosis

Abstract Background: Gastrointestinal manifestations and gut dysbiosis are prevalent after SARS-CoV2 infection.With the continuously increasing number of infected cases, more attention should be paid to this particular population in post-infection recovery.cWe aimed to investigate the potential beneficial effect of FMT on gastrointestinal symptoms, gut dysbiosis and immune status in discharged COVID-19 patients. Results: Gastrointestinal and psychological disorder (45.5%) were observed in COVID-19 patients during post-infection recovery, improvement of which were observed after FMT. Most of the lab results including blood routine and blood biochemistry, within the normal range. The general distribution of 69 different types of lymphocytes differed between before and after FMT. FMT exert significant effect on B cells which was characterized as decreased naive B cell ( P =0.012) and increased memory B cells ( P = 0.001) and non-switched B cells ( P = 0.012).The microbial community richness indicated by OTUs number, observed species and Chao1 estimators was marginally increased after FMT, whereas the community diversity estimated by the Shannon and Simpson index showed no significant changes after FMT. Gut microbiome composition of discharged COVID-19 patients differed from that of the general population at both phylum and genera level, which was characterized with a lower proportion of Firmicutes (41.0%) and Actinobacteria (4.0%), higher proportion of Bacteroidetes (42.9%) and Proteobacteriato (9.2%). FMT can partially restore the gutdysbiosis by increasing the relative abundance of Actinobacteria (15.0%) and reducing Proteobacteriato (2.8%) at the phylum level. At the genera level, Bifidobacterium and Faecalibacterium , which were dominant genera in the human gut microbiota and were beneficial for human health, had significantly increased after FMT. Conclusions: Gastrointestinal and gut dysbiosis were observed in COVID-19 patients during post-infection recovery. FMT can improve the immune functionality, restore the gut microbiota, alleviate gastrointestinal disorders, and may serve as a potential therapeutic and rehabilitative intervention for the COVID-19.

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Gut Microbiota, Antibiotic Therapy and Antimicrobial Resistance: A Narrative Review

Microorganisms ◽

10.3390/microorganisms8020269 ◽

2020 ◽

Vol 8 (2) ◽

pp. 269 ◽

Cited By ~ 4

Author(s):

Benoit Pilmis ◽

Alban Le Monnier ◽

Jean-Ralph Zahar

Keyword(s):

Antimicrobial Resistance ◽

Gut Microbiota ◽

Antibiotic Therapy ◽

Fecal Microbiota Transplantation ◽

Ecological Impact ◽

Antibiotic Consumption ◽

Epidemiological Studies ◽

Fecal Microbiota ◽

Spectrum Activity ◽

The Impact

Antimicrobial resistance is a major concern. Epidemiological studies have demonstrated direct relationships between antibiotic consumption and emergence/dissemination of resistant strains. Within the last decade, authors confounded spectrum activity and ecological effects and did not take into account several other factors playing important roles, such as impact on anaerobic flora, biliary elimination and sub-inhibitory concentration. The ecological impact of antibiotics on the gut microbiota by direct or indirect mechanisms reflects the breaking of the resistance barrier to colonization. To limit the impact of antibiotic therapy on gut microbiota, consideration of the spectrum of activity and route of elimination must be integrated into the decision. Various strategies to prevent (antimicrobial stewardship, action on residual antibiotics at colonic level) or cure dysbiosis (prebiotic, probiotic and fecal microbiota transplantation) have been introduced or are currently being developed.

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Effect of Fecal Microbiota Transplantation on Primary Hypertension and the Underlying Mechanism of Gut Microbiome Restoration: Protocol of a Randomized, Double-Blinded, Placebo-Controlled Study

10.21203/rs.3.rs-706375/v1 ◽

2021 ◽

Author(s):

Luyun Fan ◽

Jie Ren ◽

Youren Chen ◽

Yang Wang ◽

Zihong Guo ◽

...

Keyword(s):

Blood Pressure ◽

Gut Microbiota ◽

Fecal Microbiota Transplantation ◽

Blood Pressure Monitoring ◽

Fecal Microbiota ◽

Controlled Study ◽

Metagenomic Sequencing ◽

Microbial Composition ◽

Blood Pressure Elevation ◽

Double Blinded

Abstract BackgroundHypertension is in current the leading modifiable cause of global morbidity and mortality, contributing to substantial health and financial burdens. Although multiple explorations on management models and innovative therapeutic strategies of hypertension, vacancy still occur in the field with poor control rate reflected and lacking of novel, effectively clinical-translated medication or intervention options. Recent animal and human studies repeatedly confirmed a link between microbiota and hypertension. Of note is our previous study establishing a cause-and-effect relationship between gut microbiota and blood pressure elevation. A hypothesis of gut microbiota intervention on treating hypertension is thus postulated with fecal microbiota transplantation(FMT) from healthy donors performed. MethodsA multi-center, central randomized, placebo-controlled, double-blinded clinical trial is performed in 120 grade 1 hypertensive patients for overall three months. All recruited patients will be randomly assigned in a 1:1 ratio into orally-taken FMT capsules or placebo capsules with three interventions on day 1, day 7 and day 14 in separate, and followed up on day 30, day 60 and day 90. The primary outcome is the change for office systolic blood pressure from baseline to day 30 follow-up. Main secondary outcomes are BP indicators including changes in systolic and diastolic blood pressure from office, home, and 24-hour ambulatory blood pressure monitoring, assessments of ankle-branchial index and pulse wave velocity, profiling of fecal microbial composition and function, profiling of fecal and serum metabolome, changes in levels of blood glucose, blood lipids and body mass index, assessment of adverse events as a measure of safety. DiscussionStretching from our previous research on the role of gut microbiota in the pathogenesis of hypertension, this study serves as a clinical translation advancement and firstly explores the potential of fecal microbiota transplantation on treating hypertension. Underlying mechanisms particularly on anchoring specific microorganisms or their postbiotics contributing to blood pressure amelioration will also be investigated via multiple approaches such as metagenomic sequencing and metabolomic profiling.Trial registrationClinicalTrials.gov Identifier: NCT04406129, registried on May 28th, 2020, https://clinicaltrials.gov/ct2/show/NCT04406129

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