Diversity Of Intestinal Microbiome Research Articles

Metagenomic and metabolomic analyses show correlations between intestinal microbiome diversity and microbiome metabolites in ob/ob and ApoE-/- mice.

Obesity and atherosclerosis are the most prevalent metabolic diseases. ApoE-/- and ob/ob mice are widely used as models to study the pathogenesis of these diseases. However, how gut microbes, gut bacteriophages, and metabolites change in these two disease models is unclear. Here, we used wild-type C57BL/6J (Wt) mice as normal controls to analyze the intestinal archaea, bacteria, bacteriophages, and microbial metabolites of ob/ob and ApoE-/- mice through metagenomics and metabolomics. Analysis of the intestinal archaea showed that the abundances of Methanobrevibacter and Halolamina were significantly increased and decreased, respectively, in the ob/ob group compared with those in the Wt and ApoE-/- groups (p < 0.05). Compared with those of the Wt group, the relative abundances of the bacterial genera Enterorhabdus, Alistipes, Bacteroides, Prevotella, Rikenella, Barnesiella, Porphyromonas, Riemerella, and Bifidobacterium were significantly decreased (p < 0.05) in the ob/ob mice, and the relative abundance of Akkermansia was significantly decreased in the ApoE-/- group. The relative abundances of A. muciniphila and L. murinus were significantly decreased and increased, respectively, in the ob/ob and ApoE-/- groups compared with those of the Wt group (p < 0.05). Lactobacillus_ prophage_ Lj965 and Lactobacillus _ prophage _ Lj771 were significantly more abundant in the ob/ob mice than in the Wt mice. Analysis of the aminoacyl-tRNA biosynthesis metabolic pathway revealed that the enriched compounds of phenylalanine, glutamine, glycine, serine, methionine, valine, alanine, lysine, isoleucine, leucine, threonine, tryptophan, and tyrosine were downregulated in the ApoE-/- mice compared with those of the ob/ob mice. Aminoacyl-tRNA synthetases are considered manifestations of metabolic diseases and are closely associated with obesity, atherosclerosis, and type 2 diabetes. These data offer new insight regarding possible causes of these diseases and provide a foundation for studying the regulation of various food nutrients in metabolic disease models.

Accumulation of Black Carbon Particles in Placenta, Cord Blood and Childhood Urine on the Intestinal Microbiome Diversity and Composition in Four-to-Six-Year-Old Children

Accumulation of Black Carbon Particles in Placenta, Cord Blood and Childhood Urine on the Intestinal Microbiome Diversity and Composition in Four-to-Six-Year-Old Children

Dysbiosis of Gut Microbiota in Patients Undergoing Cardiac Surgery

The diversity of bacteria, viruses, eukaryotic organisms, and archaea that live in the gastrointestinal tract and have coevolved with the host over thousands of years to establish a complex and advantageous relationship is referred to as the “gut microbiota” or “gut microbiome.” The numerous and diverse gut microbiota play an important role mostly in the betterment of human health by facilitating the breakdown of food to release nutrients that would otherwise be inaccessible to the host, encouraging host cells proliferation and differentiation, defending the host against pathogen colonization, and activating or modulating the immune system. The gut microbial community plays an important role in protecting the host against pathogenic microbes, modulating immunity, and regulating metabolic processes and is even regarded as an endocrine organ. The term “dysbiosis” refers to the imbalance of the gut bacterial microbiota, which has been linked to several disorders such as cardiovascular diseases, obesity, irritable bowel syndrome, colorectal cancer, and sepsis. During cardiac surgery, intestinal ischemia-reperfusion causes an inflammatory response throughout the body. Since the intestines are an organ that is vulnerable to ischemia, germs and endotoxins can move between organs. As a consequence, the gut leads to sepsis after surgery. Next-generation sequencing technologies have enabled analysis of a large number of microorganisms. Metagenomics can be used to study intestinal microbiome diversity and dysbiosis, as well as its relationship to health and disease. Sequence-based and multifunctional metagenomics will also provide insights that will lead to greater knowledge than it is ever been of the structural and functional microbiomes.

The regulatory effect of fermented black barley on the gut microbiota and metabolic dysbiosis in mice exposed to cigarette smoke

Smoking is a global public health event that can cause oxidative stress and gut microbiota dysbiosis and is related to the occurrence of diseases such as cancer and respiratory system disease. We previously found that fermented black barley was rich in antioxidative components such as polyphenols and flavonoids and regulated gut microbiota dysbiosis. In the present study, the protective effects of fermented black barley on cigarette smoke-induced damage, such as lung, reproduction organ injury, gut microbiota and metabolic dysbiosis, were investigated. Fermented black barley (100 μL/10 g·BW per day, containing 1 × 108 CFU/mL Lactobacillus) was administered orally to male ICR mice that were regularly exposed to cigarette smoke (one time a day, 15 cigarettes each time, 30 min/time). The intervention lasted continuously for 12 weeks. The results showed that compared to the group exposed only to cigarette smoke, fermented black barley treatment alleviated the pathological damage to lung and testis tissues and significantly increased the total sperm motility and antioxidative capacity of the lung. Fermented black barley also regulated the intestinal microbiome diversity; reduced the relative abundances of Lactobacillus, Turicibacter and Bifidobacterium; and increased the relative abundances of Oscillospira and Ruminococcus at the genus level. Furthermore, the metabolic profile was investigated via analysis of the abundances of fecal and hepatic metabolites, and it was shown that fermented black barley treatment alleviated the metabolic dysbiosis of lipids, amino acids, and the biosynthesis of steroid hormones (such as dehydroepiandrosterone sulfate, etc.) induced by cigarette smoking, which approached normal conditions. These regulatory effects may partially elucidate the beneficial role of fermented black barley in alleviating the harmful effects of cigarette smoking. In summary, supplementation with fermented cereal food may be a helpful way to ameliorate cigarette smoking-induced damage.

Impacts of conventional and biodegradable microplastics on juvenile Lates calcarifer: Bioaccumulation, antioxidant response, microbiome, and proteome alteration

Discarded plastic bag is a main component of marine debris, posing potential threats to marine biota. This study was conducted to assess the potential effects of microplastics on juvenile Lates calcarifer. Fish were exposed via diet to two microplastic types from conventional polyethylene (PE) and biodegradable (Bio) plastic bags for 21 days. Antioxidative enzymes activity, intestinal microbiome and proteome were determined. PE and Bio microplastics were found to accumulate in gastrointestinal tracts, and no mortality was observed. Microplastics exposure did not induce significant antioxidant response except for the glutathione reductase (GR) modulation. Intestinal microbiome diversity decreased significantly in PE group based on Simpson index. Both types of microplastics induced proteome modulation by down-regulating proteins associated with immune homeostasis. Bio microplastics maintained higher intestinal microbial diversity and induced more proteins alteration than PE microplastics. This study provides toxicological insights into the impacts of conventional and biodegradable microplastics on juvenile L. calcarifer.

Microbiome structure in large pelagic sharks with distinct feeding ecologies

BackgroundSharks play essential roles in ocean food webs and human culture, but also face population declines worldwide due to human activity. The relationship between sharks and the microbes on and in the shark body is unclear, despite research on other animals showing the microbiome as intertwined with host physiology, immunity, and ecology. Research on shark-microbe interactions faces the significant challenge of sampling the largest and most elusive shark species. We leveraged a unique sampling infrastructure to compare the microbiomes of two apex predators, the white (Carcharodon carcharias) and tiger shark (Galeocerdo cuvier), to those of the filter-feeding whale shark (Rhincodon typus), allowing us to explore the effects of feeding mode on intestinal microbiome diversity and metabolic function, and environmental exposure on the diversity of microbes external to the body (on the skin, gill).ResultsThe fecal microbiomes of white and whale sharks were highly similar in taxonomic and gene category composition despite differences in host feeding mode and diet. Fecal microbiomes from these species were also taxon-poor compared to those of many other vertebrates and were more similar to those of predatory teleost fishes and toothed whales than to those of filter-feeding baleen whales. In contrast, microbiomes of external body niches were taxon-rich and significantly influenced by diversity in the water column microbiome.ConclusionsThese results suggest complex roles for host identity, diet, and environmental exposure in structuring the shark microbiome and identify a small, but conserved, number of intestinal microbial taxa as potential contributors to shark physiology.

Intestinal morphology and microflora to Vibrio alginolyticus in pacific white shrimp (Litopenaeus vannamei)

In recent years, the shrimp farming industry encountered significant economic losses induced by Vibrio alginolyticus. In this study, the influence of Vibrio alginolyticus on intestinal histomorphology and microbiome composition in Litopenaeus vannamei were studied. The results showed that the intestinal mucosal epithelial cells of Vibrio group (VA group) injected only with Vibrio alginolyticus showed large area exfoliation at 12 h, and the tissue morphology of intestine recovered at 48 h. Compared with the control group (CK group), the abundance of Proteobacteria was significantly higher (P < 0.05), while the abundance of Actinobacteria was significantly lower after infection with Vibrio alginolyticus. The abundance of Shewanella in intestinal microbiome of Litopenaeus vannamei was significantly higher at 12 h (P < 0.05), but the abundance of Candidatus_Bacilloplasma was significantly lower at 48 h after infection (P < 0.05). In VA group, the diversity of intestinal microbiome was significantly lower at 12 h, which could be caused by the proliferation of Candidatus_Bacilloplasma and Shewanella. All above findings suggested that the stability of the dynamic balance of microbiome in the intestine helped Litopenaeus vannamei to resist pathogen colonization.

Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis.

Little is known about how interactions of diet, intestinal stem cells (ISCs), and immune cells affect early-stage intestinal tumorigenesis. We show that a high-fat diet (HFD) reduces the expression of the major histocompatibility complex class II (MHC class II) genes in intestinal epithelial cells, including ISCs. This decline in epithelial MHC class II expression in a HFD correlates with reduced intestinal microbiome diversity. Microbial community transfer experiments suggest that epithelial MHC class II expression is regulated by intestinal flora. Mechanistically, pattern recognition receptor (PRR) and interferon-gamma (IFNγ) signaling regulates epithelial MHC class II expression. MHC class II-negative (MHC-II-) ISCs exhibit greater tumor-initiating capacity than their MHC class II-positive (MHC-II+) counterparts upon loss of the tumor suppressor Apc coupled with a HFD, suggesting a role for epithelial MHC class II-mediated immune surveillance in suppressing tumorigenesis. ISC-specific genetic ablation of MHC class II increases tumor burden cell autonomously. Thus, HFD perturbs a microbiome-stem cell-immune cell interaction that contributes to tumor initiation in the intestine.

S131 CP101, an Investigational Orally Administered Microbiome Therapeutic, Increases Intestinal Microbiome Diversity and Prevents Recurrent C. difficile Infection: Results From a Randomized, Placebo-Controlled Trial

S131 CP101, an Investigational Orally Administered Microbiome Therapeutic, Increases Intestinal Microbiome Diversity and Prevents Recurrent C. difficile Infection: Results From a Randomized, Placebo-Controlled Trial

Effects of Heat Stress on Gut Microbiome in Rats

Gut microbiome, as the largest and most important micro-ecosystem, plays a critical role in health. The purpose of this study was to evaluate whether heat stress modulates the composition and diversity of the gut microbiome in rats. The heat stress model was prepared in rats with the heating temperature maintained at 35–38°C. Cecum contents were collected after heat stress for 3 h and days 1, 3 and 7. Total DNA was extracted for 16 S rRNA sequencing and analysis of intestinal microbiome composition and diversity. The study showed that the composition of the intestinal microbiome of heat stress group was changed. And the heat stress modulated key phylotypes of gut microbiota at the level of phylum and genus. In particular, the genus of Lactobacillus and Bacteroides were significantly reduced, whereas the Oscillospira and Clostridium were increased by heat stress. Meanwhile, the rats under the heat stress encountered the change in carbohydrate metabolism, amino acid metabolism, and membrane transport to defense against stress. Taken together, the composition and structure of gut microbiome were affected by heat stress and some key phylotypes were also significantly altered. We conclude that the heat stress could impact multiple biological functions, via altering the gut microbiome.

P048 Intestinal inflammation and microbiome diversity are conserved more in consecutive pregnancies among women with inflammatory bowel disease compared to healthy controls

Abstract Background There are increasing data on changes in intestinal inflammation and microbiome diversity during pregnancy in women with inflammatory bowel disease (IBD) with implications towards individual and offspring immune function. However, differences in intestinal inflammation, as measured by fecal calprotectin (FC) and microbial a-diversity, in consecutive pregnancies are not known. Methods We prospectively enrolled a cohort of women, 37 with IBD and 39 without IBD, during two consecutive pregnancies, and their offspring. We collected serial stool samples and clinical data, and measured FC and bacterial abundance during each trimester of each pregnancy. We further performed correlation analysis between FC in consecutive pregnancies and between microbial a-diversity in consecutive pregnancies among women with and without IBD. Results Compared to healthy controls, IBD pregnancies had significantly lower gestational age at birth and higher frequency of Cesarean section. Mode of delivery, the status of Group B Streptococcus (GBS) infection and GBS infection prophylaxis were significantly associated with the pregnancy order in both IBD and controls (Table). Furthermore, we observed strong correlations of FC (r=0.56, p-value=0.093) and microbial alpha-diversity assessed as operational taxonomic unit (OTU) richness (r=0.88, p=0.0087) between paired consecutive pregnancies in women with IBD, but not in those without IBD (Figure). There were no differences in microbial alpha-diversity using the Shannon and Simpson indices when comparing consecutive pregnancies of women with and without IBD. Conclusion In this study, we demonstrate that intestinal inflammation and microbiome diversity are more conserved in consecutive pregnancies of women with IBD compared to healthy controls. These findings may have implications towards understanding the impact of pregnancy on host-microbiome interactions in IBD as well as the potential impact on offspring health.

Effects of Sevoflurane Inhalation Anesthesia on the Intestinal Microbiome in Mice.

In recent years, more and more attention has been paid to intestinal microbiome. Almost all operations will go through the anesthesia process, but it is not clear whether the intervention of anesthesia alone will affect the change in the intestinal microbiome. The purpose of this study was to verify the effect of sevoflurane inhalation anesthesia on the intestinal microbiome. The animal in the experimental group was used to provide sevoflurane inhalation anesthesia for 4 hours. The control group was not intervened. The feces of the experimental group and the control group were collected on the 1st, 3rd, 7th and 14th days after anesthesia. Sevoflurane inhalation anesthesia will cause changes in the intestinal microbiome of mice. It appears on the 1st day after anesthesia and is most obvious on the 7th day. The specific manifestation is that the abundance of microbiome and the diversity of the microbiome is reduced. At the same time, Untargeted metabonomics showed that compared with the control group, the experimental group had more increased metabolites related to the different microbiome, among which 5-methylthioadenosine was related to the central nervous system. Subsequently, the intestinal microbiome diversity of mice showed a trend of recovery on the 14th day. At the genus level, the fecal samples obtained on the 14th day after anesthesia exhibited significantly increased abundances of Bacteroides, Alloprevotella, and Akkermansia and significantly decreased abundances of Lactobacillus compared with the samples obtained on the 1st day after anesthesia. However, the abundance of differential bacteria did not recover with the changing trend of diversity. Therefore, we believe that sevoflurane inhalation anesthesia is associated with changes in the internal microbiome and metabolites, and this change may be completed through the brain-gut axis, while sevoflurane inhalation anesthesia may change the intestinal microbiome for as long as 14 days or longer.

Decreased Intestinal Microbiome Diversity in Pediatric Sepsis: A Conceptual Framework for Intestinal Dysbiosis to Influence Immunometabolic Function.

The intestinal microbiome can modulate immune function through production of microbial-derived short-chain fatty acids. We explored whether intestinal dysbiosis in children with sepsis leads to changes in microbial-derived short-chain fatty acids in plasma and stool that are associated with immunometabolic dysfunction in peripheral blood mononuclear cells. Prospective observational pilot study. Single academic PICU. Forty-three children with sepsis/septic shock and 44 healthy controls. Stool and plasma samples were serially collected for sepsis patients; stool was collected once for controls. The intestinal microbiome was assessed using 16S ribosomal RNA sequencing and alpha- and beta-diversity were determined. We measured short-chain fatty acids using liquid chromatography, peripheral blood mononuclear cell mitochondrial respiration using high-resolution respirometry, and immune function using ex vivo lipopolysaccharide-stimulated whole blood tumor necrosis factor-α. Sepsis patients exhibited reduced microbial diversity compared with healthy controls, with lower alpha- and beta-diversity. Reduced microbial diversity among sepsis patients (mainly from lower abundance of commensal obligate anaerobes) was associated with increased acetic and propionic acid and decreased butyric, isobutyric, and caproic acid. Decreased levels of plasma butyric acid were further associated with lower peripheral blood mononuclear cell mitochondrial respiration, which in turn, was associated with lower lipopolysaccharide-stimulated tumor necrosis factor-α. However, neither intestinal dysbiosis nor specific patterns of short-chain fatty acids were associated with lipopolysaccharide-stimulated tumor necrosis factor-α. Intestinal dysbiosis was associated with altered short-chain fatty acid metabolites in children with sepsis, but these findings were not linked directly to mitochondrial or immunologic changes. More detailed mechanistic studies are needed to test the role of microbial-derived short-chain fatty acids in the progression of sepsis.

Wastewater treatment works change the intestinal microbiomes of insectivorous bats.

Mammals, born with a near-sterile intestinal tract, are inoculated with their mothers’ microbiome during birth. Thereafter, extrinsic and intrinsic factors shape their intestinal microbe assemblage. Wastewater treatment works (WWTW), sites synonymous with pollutants and pathogens, receive influent from domestic, agricultural and industrial sources. The high nutrient content of wastewater supports abundant populations of chironomid midges (Diptera), which transfer these toxicants and potential pathogens to their predators, such as the banana bat Neoromicia nana (Vespertilionidae), thereby influencing their intestinal microbial assemblages. We used next generation sequencing and 16S rRNA gene profiling to identify and compare intestinal bacteria of N. nana at two reference sites and two WWTW sites. We describe the shared intestinal microbiome of the insectivorous bat, N. nana, consisting of seven phyla and eleven classes. Further, multivariate analyses revealed that location was the most significant driver (sex, body size and condition were not significant) of intestinal microbiome diversity. Bats at WWTW sites exhibited greater intestinal microbiota diversity than those at reference sites, likely due to wastewater exposure, stress and/or altered diet. Changes in their intestinal microbiota assemblages may allow these bats to cope with concomitant stressors.

Association between Gut Microbial Diversity and Carotid Intima-Media Thickness.

Background and Objectives: There is an increasing focus on the effect of the gut microbiome on developing atherosclerosis, but there is still no unified standpoint. We aimed to find associations between intestinal microbiome diversity and a marker of subclinical atherosclerosis, the carotid intima-media thickness (IMT). Materials and Methods: Recruited from the Hungarian Twin Registry, 108 monozygotic (MZ) twins (mean age 52.4 ± 14.1 years, 58% female) underwent a comprehensive carotid ultrasound examination (Samsung RS85). Of the 108 MZ twins, 14 pairs (mean age 65 ± 6.4 years, 71% female) discordant for carotid IMT were selected to undergo a stool sample collection. A special stool sampling container was mailed and received from each participant. After DNA extraction, library construction was performed specifically for the V3–V4 hypervariable region of microbial 16S rRNA. Next, the microbiome composition of the samples was determined using Kraken software. Two hypotheses were tested with the exact permutation test: (1) in the group with normal IMT, the Shannon index of the phyla is higher; and (2) the Firmicutes/Bacteroidetes ratio is greater in the group with high IMT values. Furthermore, the abundance of different bacterial strains present at higher and normal IMT was also explored. Statistical analysis was carried out using R software. Results: Increased Firmicutes/Bacteroidetes ratio was associated with increased IMT (mean Firmicutes/Bacteroidetes ratio of IMT > 0.9 and IMT < 0.9 groups: 2.299 and 1.436, respectively; p = 0.031). In the group with normal IMT values, a substantially higher fraction of Prevotellaceae was observed in contrast with subjects having subclinical atherosclerosis. However, there was no significant difference in the alpha diversity between the two groups. Conclusions: The determining role of individual genera and their proportions in the development and progression of atherosclerosis can be assumed. Further studies are needed to clarify if these findings can be used as potential therapeutic targets.

Gut Microbiome of Children and Adolescents With Primary Sclerosing Cholangitis in Association With Ulcerative Colitis.

Few studies reported the relation of intestinal microbiome composition and diversity in pediatric patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC). In this cross-sectional study, we selected patients younger than 19 years old from the pediatric gastroenterology and hepatology outpatient clinic of a tertiary hospital to describe the intestinal microbiome of pediatric patients with PSC associated or not to UC. Patients were divided in PSC, PSC+UC, and UC diagnosis. A stool sample was collected from each patient (n=30) and from a healthy relative/neighbor (n=23). The microbiome composition was assessed using MiSeq (Illumina) platform. Differences in microbial composition were found between PSC and PSC+UC groups. The relative abundance of Veillonella and Megasphaera genera were increased depending on patients’ age at diagnosis. Veillonella was also increased in patients who were in an active status of the disease. Both genera were positively correlated to total bilirubin and gamma-glutamyl transferase. As a conclusion, the disease, the age and the disease activity status seem to influence the intestinal microbiome, highlighting the difference of intestinal microbiome profile for patients depending on age at diagnosis. We also showed an increase of Veillonella in patients with PSC and PSC+UC, and a positive correlation of dysbiosis and higher gamma-glutamyl transferase and total bilirubin in PSC+UC patients. Our findings are promising in the diagnosis, prognosis, and future therapeutic perspectives for PSC patients.

Effect of temperature stress on gut-brain axis in mice: Regulation of intestinal microbiome and central NLRP3 inflammasomes

BackgroundTemperature stress was reported to impact the gut-brain axis including intestinal microbiome and neuroinflammation, but the molecular markers involved remain unclear. We aimed to examine the effects of different temperature stress on the intestinal microbiome and central nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes. Materials and methodsMice models were established under low temperature (LT), room temperature (RT), high temperature (HT), and temperature variation (TV) respectively for seven days. We examined temperature-induced changes of intestinal microbiome composition and the levels of its metabolites short-chain fatty acids (SCFAs), as well as the expressions of central NLRP3 inflammasomes and inflammatory cytokines. Redundancy analysis and Spearman correlation analysis were performed to explore the relationships between microbiome and NLRP3 inflammasomes and other indicators. ResultsHT and LT significantly increased the Alpha diversity of intestinal microbiome. Compared with RT group, Bacteroidetes were most abundant in LT group while Actinobacteria were most abundant in HT and TV groups. Nineteen discriminative bacteria were identified among four groups. LT increased the expressions of acetate and propionate while decreased that of NLRP3 inflammasomes; HT decreased the expression of butyrate while increased that of NLRP3 inflammasomes, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α; TV decreased the expression of propionate while increased that of NLRP3 inflammasomes and TNF-α. Microbiome distribution could significantly explain the differences in NLRP3 between comparison groups (LT&RT: R2 = 0.82, HT&RT: R2 = 0.86, TV&RT: R2 = 0.94; P < 0.05). The discriminative bacteria were significantly correlated with SCFAs but were correlated with NLRP3 inflammasomes and cytokines in the opposite direction. ConclusionsLT inhibits while HT and TV promote the activation of NLRP3 inflammasomes in brain, and intestinal microbiome and its metabolites may be the potential mediators. Findings may shed some light on the impact of temperature stress on gut-brain axis.

Poszukiwanie przyczyn oporności na immunoterapię pembrolizumabem u chorej na gruczołowego raka płuca z ekspresją PD-L1 – mikrobiom jelitowy „pod lupą”

Anti-PD-1 or PD-L1 immunotherapy in some patients with non-small cell lung cancer (NSCLC) may not be effective, despite the high percentage of cancer cells with PD-L1 expression (≥ 50%). TMB (tumor mutation burden), smoking status and low intestinal microbiome diversity may be associated with lack of efficacy of immune checkpoints inhibitors treatment in NSCLC patients. The case presented here concerns a non-smoking female patient with lung adenocarcinoma, in whom, despite the high percentage of PD-L1 positive tumor cells (50%), pembrolizumab therapy was ineffective. Next generation sequencing (NGS) was performed using the FOCUS panel allowing the analysis of 52 genes whose damage is associated with various types of solid tumors, including lung cancer. Benign genetic changes clinically irrelevant for patients with non-small cell lung cancer have been observed. In the meantime, profiling of the patient’s intestinal microbiome was performed, due to the fact that the composition of the intestinal microbiome may be a decisive factor in the lack of response to immunotherapy in patients with high PD-L1 expression and no driver mutations. Low diversity of bacteria in the intestines, with a noticeable dysbiosis (dysbacteriosis), was observed. The presence of bacteria Akkermansia, Enterococcaceae, Bifidobacteriaceae or Coriobacteriaceae , especially the presence of Akkermansia mucinifila seems to be a favourable factor of the possibility of obtaining response to immunotherapy and prolongation of progression-free survival (PFS). In the intestinal microbiome of the presented case, no bacteria from the Verrucomicrobia phylum , to which A. mucinifila belongs , were found. In addition, only 0.011% of Enterococcaceae were found. Studies on the intestinal microbiome in cancer patients receiving immunotherapy appear to be necessary to correctly understand the effect of microbiome composition on the effectiveness of this treatment method.

Omitting Fluoroquinolones Antibiotic Prophylaxis in Allogeneic Hematopoietic Stem Cell Transplantation Does Not Increase Gram-Negative Bacteremia Rate or Transplant-Related Mortality

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is widely utilized as a curative treatment for malignant and non-malignant hematological conditions. Fluoroquinolone prophylaxis (FQ-P) is demonstrated to reduce the rate of blood stream infections (BSI) caused by gram-negative bacteria (GNB) during allo-HSCT and increases overall survival (OS), making this approach the standard of care. The available data show that during the transplantation period, the intestinal microbiome diversity profoundly decreases, which is associated with a significant increase in transplant-related mortality (TRM), acute graft-versus-host disease (aGVHD) related mortality and decrease in OS. FQ-P is reported to be a dominant factor in the perturbation of the gut microbiota, leading some centers to omit or modify transplant antibiotic prophylaxis regimens. The aim of the present study has been to evaluate the effects of FQ-P omission on the prevalence of gram-negative bacteria blood stream infections (GNB-BSI), GNB susceptibility to antibiotic treatment, mortality of patients with sepsis and overall TRM. This retrospective single-center study included all consecutive patients, admitted to the Rambam Department of Hematology for allo-HSCT between 01.01.2017 and 31.12.2019. The fact that at our center, FQ-P in allo-HSCT recipients was discontinued on 01.12.2018 allowed comparison of the outcomes in patients treated with and without such prophylaxis. GNB-BSI events registered within 30 days of admission were analyzed. The proportion of first-time GNB-BSI, the antibiotic susceptibility profile, day 30 and day 90 mortality among patients with GNB-BSI were compared. The assessment also included day 30 and day 90 overall TRM, mortality related to sepsis and aGVHD. During the evaluated period, 189 patients underwent allo-HSCT and were included in the analysis. FQ-P was administered to 125 patients and omitted in 64 individuals. GNB-BSI events occurred in 23 (18.4%) patients receiving FQ-P and in 17 (26.6%) patients who did not receive it (p=0.19). GNB susceptibility to FQ, piperacillin/tazobactam and meropenem increased from 38.1% to 58.8%, from 60% to 70.6% and from 85.7% to 94.1%, respectively, after FQ-P had been stopped (p=non-significant, NS). 30-day and 90-day mortality among patients with GNB-BSI did not increase in the post-FQ-P period (Table 1). Day 30 and day 90 overall TRM rates were 10.6% and 18.9%, respectively, with FQ-P versus 13.5% and 21.9%, respectively, without FQ-P (p=NS). Before FQ-P was stopped, sepsis was the cause of death in 56% of events and aGVHD in 16% and after FQ-P was stopped, the corresponding values were 46% and 23%, respectively (p=NS). FQ-P omission has not significantly increased the rate of GNB-BSI or affected the profile of GNB susceptibility to antibiotic treatment in patients undergoing allo-HSCT. Moreover, it has not significantly changed day 30 and day 90 mortality either among patients with GNB-BSI or in the entire study population. FQ-P omission in allo-HSCT recipients appears to be safe and its implementation could contribute to the preservation of intestinal microbiome diversity, potentially leading to improved post-transplant outcome. The findings of this study need to be further evaluated in large randomized trials. Disclosures No relevant conflicts of interest to declare.

Effects of Rearing Conditions and Sex on Cecal Microbiota in Ducks.

The intestinal microbiome influences the health of animals. However, little is known about the impact of indoor conditions and sex on intestinal microbiome diversity and composition in ducks. The present study aimed to investigate differences in the cecal microbiome between male and female ducks reared on the floor (PY group) or in cages (LY group). We also determined the relationships between cecal microbiota composition and slaughter traits, and the expression levels of mucosal and intestinal structural genes in ducks. There was a slight difference in slaughter traits among the groups, with cecum weight being significantly lighter in the LY compared with the PY group, especially in females (p < 0.05). Analysis of the alpha diversity of the cecal microbiota between males and females in the LY and PY groups showed that LY males had significantly lower diversity and richness. Beta diversity analysis demonstrated differences in the microbiota composition in relation to rearing conditions, and a significant difference between the sexes in the PY groups. The dominant bacterial phyla in duck cecum were Bacteroidetes, Firmicutes, Proteobacteria, and Fusobacteria. The relative abundances of the most common bacteria revealed that the intestinal microbiota diversity and composition were affected by both feeding conditions and sex. Several bacterial genera were detected differentially among the groups. These genera were correlated with slaughter traits and expression levels of mucosal and cecal structural genes in ducks. In conclusion, rearing conditions, sex, and associated changes in the cecal microbiota are thus associated with gut barrier functions in ducks.