scholarly journals Modulation of the Gut Microbiota Alters the Tumor-Suppressive Efficacy of Tim-3 Pathway Blockade in a Bacterial Species- and Host Factor-Dependent Manner

2020 ◽  
Author(s):  
Bokyoung Lee ◽  
Jieun Lee ◽  
Min-Yeong Woo ◽  
Mi Jin Lee ◽  
Ho-Joon Shin ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Bacterial Species ◽  
Alpha Diversity ◽  
16S Rrna Gene Sequencing ◽  
Mouse Strains ◽  
Rrna Gene ◽  
Antibiotic Administration ◽  
Dependent Manner ◽  
Oral Gavage ◽  
Anti Cancer

Abstract Background T cell immunoglobulin and mucin domain-containing protein-3 (Tim-3) is an immune checkpoint molecule and a potential target for anti-cancer therapy. Alterations in the tumor-suppressive efficacy of immunotherapy due to gut microbiota disturbance have been reported; however, the influence of gut microbiota on the efficacy of Tim-3 blockade is yet to be investigated. In this study, we examined whether gut microbiota manipulation altered the anti-tumor efficacy of Tim-3 blockade. The gut microbiota was manipulated by the administration of antibiotics and oral gavage of bacteria to mice. Results Alterations in the gut microbiome were analyzed by 16S rRNA gene sequencing. Gut dysbiosis triggered by antibiotics attenuated the anti-tumor efficacy of Tim-3 blockade in both C57BL/6 and BALB/c mouse strains. Anti-tumor efficacy was restored via gut microbiota manipulation through oral gavage of fecal bacteria even as antibiotic administration continued. In the case of oral gavage of Enterococcus hirae or Lactobacillus johnsonii, the transferred bacterial species and host mouse strain were critical in determining the anti-tumor efficacy of Tim-3 blockade. Furthermore, oral bacterial gavage did not increase alpha diversity of the gut microbiota in antibiotics-treated mice but did alter microbiome composition, which was associated with restoration of anti-tumor efficacy of Tim-3 blockade. Conclusions Our results highlight the importance of the gut microbiota in anti-cancer immunotherapy responsiveness and indicate that gut microbiota modulation may increase the efficacy of immunotherapy when concomitantly administered with antibiotics. The administered bacterial species and host factors should be considered so as to benefit from gut microbiota modulation.

scholarly journals Modulation of the Gut Microbiota Alters the Tumour-Suppressive Efficacy of Tim-3 Pathway Blockade in a Bacterial Species- and Host Factor-Dependent Manner

2020 ◽  
Vol 8 (9) ◽  
pp. 1395
Author(s):  
Bokyoung Lee ◽  
Jieun Lee ◽  
Min-Yeong Woo ◽  
Mi Jin Lee ◽  
Ho-Joon Shin ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Bacterial Species ◽  
Alpha Diversity ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Antibiotic Administration ◽  
Dependent Manner ◽  
Oral Gavage ◽  
Microbiome Composition ◽  
Checkpoint Molecule

T cell immunoglobulin and mucin domain-containing protein-3 (Tim-3) is an immune checkpoint molecule and a target for anti-cancer therapy. In this study, we examined whether gut microbiota manipulation altered the anti-tumour efficacy of Tim-3 blockade. The gut microbiota of mice was manipulated through the administration of antibiotics and oral gavage of bacteria. Alterations in the gut microbiome were analysed by 16S rRNA gene sequencing. Gut dysbiosis triggered by antibiotics attenuated the anti-tumour efficacy of Tim-3 blockade in both C57BL/6 and BALB/c mice. Anti-tumour efficacy was restored following oral gavage of faecal bacteria even as antibiotic administration continued. In the case of oral gavage of Enterococcus hirae or Lactobacillus johnsonii, transferred bacterial species and host mouse strain were critical determinants of the anti-tumour efficacy of Tim-3 blockade. Bacterial gavage did not increase the alpha diversity of gut microbiota in antibiotic-treated mice but did alter the microbiome composition, which was associated with the restoration of the anti-tumour efficacy of Tim-3 blockade. Conclusively, our results indicate that gut microbiota modulation may improve the therapeutic efficacy of Tim-3 blockade during concomitant antibiotic treatment. The administered bacterial species and host factors should be considered in order to achieve therapeutically beneficial modulation of the microbiota.

scholarly journals Developmental, Dietary, and Geographical Impacts on Gut Microbiota of Red Swamp Crayfish (Procambarus clarkii)

2020 ◽  
Vol 8 (9) ◽  
pp. 1376
Author(s):  
Zhenting Zhang ◽  
Jiali Liu ◽  
Xuexia Jin ◽  
Chao Liu ◽  
Chenwei Fan ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Procambarus Clarkii ◽  
Geographical Location ◽  
Alpha Diversity ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Dependent Manner ◽  
Red Swamp Crayfish ◽  
Fermented Feed ◽  
Rrna Gene Sequencing

Red swamp crayfish (Procambarus clarkii) breeding is an important economic mainstay in Hubei province, China. However, information on the gut microbiota of the red swamp crayfish is limited. To address this issue, the effect of developmental stage, diet (fermented or non-fermented feed), and geographical location on the gut microbiota composition in the crayfish was studied via high-throughput 16S rRNA gene sequencing. The results revealed that the dominant phyla in the gut of the crayfish were Proteobacteria, Bacteroidetes,Firmicutes, Tenericutes, and RsaHF231. The alpha diversity showed a declining trend during development, and a highly comparable gut microbiota clustering was identified in a development-dependent manner. The results also revealed that development, followed by diet, is a better key driver for crayfish gut microbiota patterns than geographical location. Notably, the relative abundance of Bacteroidetes was significantly higher in the gut of the crayfish fed with fermented feed than those fed with non-fermented feed, suggesting the fermented feed can be important for the functions (e.g., polysaccharide degradation) of the gut microbiota. In summary, our results revealed the factors shaping gut microbiota of the crayfish and the importance of the fermented feed in crayfish breeding.

scholarly journals The Influence of Diet and Sex on the Gut Microbiota of Lean and Obese JCR:LA-cp Rats

2021 ◽  
Vol 9 (5) ◽  
pp. 1037
Author(s):  
Craig Resch ◽  
Mihir Parikh ◽  
J. Alejandro Austria ◽  
Spencer D. Proctor ◽  
Thomas Netticadan ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Control Diet ◽  
Bacterial Species ◽  
Alpha Diversity ◽  
Short Chain Fatty Acids ◽  
Female Rats ◽  
Dependent Manner ◽  
Male And Female ◽  
Ground Flaxseed ◽  
The Impact

There is an increased interest in the gut microbiota as it relates to health and obesity. The impact of diet and sex on the gut microbiota in conjunction with obesity also demands extensive systemic investigation. Thus, the influence of sex, diet, and flaxseed supplementation on the gut microbiota was examined in the JCR:LA-cp rat model of genetic obesity. Male and female obese rats were randomized into four groups (n = 8) to receive, for 12 weeks, either (a) control diet (Con), (b) control diet supplemented with 10% ground flaxseed (CFlax), (c) a high-fat, high sucrose (HFHS) diet, or (d) HFHS supplemented with 10% ground flaxseed (HFlax). Male and female JCR:LA-cp lean rats served as genetic controls and received similar dietary interventions. Illumine MiSeq sequencing revealed a richer microbiota in rats fed control diets rather than HFHS diets. Obese female rats had lower alpha-diversity than lean female; however, both sexes of obese and lean JCR rats differed significantly in β-diversity, as their gut microbiota was composed of different abundances of bacterial types. The feeding of an HFHS diet affected the diversity by increasing the phylum Bacteroidetes and reducing bacterial species from phylum Firmicutes. Fecal short-chain fatty acids such as acetate, propionate, and butyrate-producing bacterial species were correspondingly impacted by the HFHS diet. Flax supplementation improved the gut microbiota by decreasing the abundance of Blautia and Eubacterium dolichum. Collectively, our data show that an HFHS diet results in gut microbiota dysbiosis in a sex-dependent manner. Flaxseed supplementation to the diet had a significant impact on gut microbiota diversity under both flax control and HFHS dietary conditions.

scholarly journals Effects of Psychotropics on the Microbiome in Patients With Depression and Anxiety: Considerations in a Naturalistic Clinical Setting

2020 ◽  
Author(s):  
Yoshihiro Tomizawa ◽  
Shunya Kurokawa ◽  
Daiki Ishii ◽  
Katsuma Miyaho ◽  
Chiharu Ishii ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Microbial Diversity ◽  
Depressive Disorders ◽  
Alpha Diversity ◽  
16S Rrna Gene Sequencing ◽  
Shannon Index ◽  
Rrna Gene ◽  
Depression And Anxiety ◽  
The Impact ◽  
Whole Tree

Abstract Background The antibacterial effects of psychotropics may be part of their pharmacological effects when treating depression. However, limited studies have focused on gut microbiota in relation to prescribed medication. Method We longitudinally investigated the relationship between patients’ prescribed medications and intestinal bacterial diversity in a naturalistic treatment course for patients with major depressive disorders and anxiety disorders. Patients were recruited and their stool was collected at 3 time points during their usual psychiatric treatments. Gut microbiota were analyzed using 16S rRNA gene sequencing. We examined the impact of psychotropics (i.e., antidepressants, anxiolytics, antipsychotics) on their gut microbial diversity and functions. Results We collected 246 stool samples from 40 patients. Despite no differences in microbial diversity between medication groups at the baseline, over the course of treatment, phylogenic diversity whole-tree diversity decreased in patients on antipsychotics compared with patients without (P = .027), and beta diversity followed this trend. Based on a fixed-effect model, antipsychotics predicted microbial diversity; the higher doses correlated with less diversity based on the Shannon index and phylogenic diversity whole tree (estimate = −0.00254, SE = 0.000595, P < .0001; estimate = −0.02644, SE = 0.00833, P = .002, respectively). Conclusion Antipsychotics may play a role in decreasing the alpha diversity of the gut microbiome among patients with depression and anxiety, and our results indicate a relationship with medication dosage. Future studies are warranted and should consider patients’ types and doses of antipsychotics in order to further elucidate the mechanisms of gut-brain interactions in psychiatric disorders.

scholarly journals Inbreeding Alters the Gut Microbiota of the Banna Minipig

Animals ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 2125
Author(s):  
Limin Wei ◽  
Bo Zeng ◽  
Siyuan Zhang ◽  
Feng Li ◽  
Fanli Kong ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gene Sequencing ◽  
Alpha Diversity ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Rrna Gene Sequencing ◽  
Isoleucine Metabolism ◽  
Dominant Bacteria ◽  
The Impact ◽  
Predicted Function

The gut microbiota coevolve with the host and can be stably transmitted to the offspring. Host genetics plays a crucial role in the composition and abundance of gut microbiota. Inbreeding can cause a decrease of the host’s genetic diversity and the heterozygosity. In this study, we used 16S rRNA gene sequencing to compare the differences of gut microbiota between the Diannan small-ear pig and Banna minipig inbred, aiming to understand the impact of inbreeding on the gut microbiota. Three dominant bacteria (Stenotrophlomonas, Streptococcus, and Lactobacillus) were steadily enriched in both the Diannan small-ear pig and Banna minipig inbred. After inbreeding, the gut microbiota alpha diversity and some potential probiotics (Bifidobacterium, Tricibacter, Ruminocaccae, Christensenellaceae, etc.) were significantly decreased, while the pathogenic Klebsiella bacteria was significantly increased. In addition, the predicted metagenomic analysis (PICRUSt2) indicated that several amino acid metabolisms (‘‘Valine, leucine, and isoleucine metabolism’’, ‘‘Phenylalanine, tyrosine, and tryptophan biosynthesis’’, ‘‘Histidine metabolism’’) were also markedly decreased after the inbreeding. Altogether our data reveal that host inbreeding altered the composition and the predicted function of the gut microbiome, which provides some data for the gut microbiota during inbreeding.

scholarly journals Dietary Correlates of Oral and Gut Microbiota in the Water Monitor Lizard, Varanus salvator (Laurenti, 1768)

2022 ◽  
Vol 12 ◽  
Author(s):  
Yu Du ◽  
Jun-Qiong Chen ◽  
Qian Liu ◽  
Jian-Chao Fu ◽  
Chi-Xian Lin ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Water Environment ◽  
Alpha Diversity ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Oral Microbiota ◽  
Monitor Lizard ◽  
Varanus Salvator ◽  
In The Wild ◽  
Monitor Lizards

Numerous studies have demonstrated that food shapes the structure and composition of the host’s oral and gut microbiota. The disorder of oral and gut microbiota may trigger various host diseases. Here, we collected oral and gut samples from wild water monitor lizards (Varanus salvator) and their captive conspecifics fed with bullfrogs, eggs, and depilated chicken, aiming to examine dietary correlates of oral and gut microbiota. We used the 16S rRNA gene sequencing technology to analyze the composition of the microbiota. Proteobacteria and Bacteroidota were the dominant phyla in the oral microbiota, and so were in the gut microbiota. The alpha diversity of microbiota was significantly higher in the gut than in the oral cavity, and the alpha diversity of oral microbiota was higher in captive lizards than in wild conspecifics. Comparing the relative abundance of oral and gut bacteria and their gene functions, differences among different animal groups presumably resulted from human contact in artificial breeding environments and complex food processing. Differences in gene function might be related to the absolute number and/or the taxonomic abundance of oral and gut microorganisms in the wild and the water environment. This study provides not only basic information about the oral and gut microbiota of captive and wild water monitor lizards, but also an inference that feeding on frogs and aquatic products and reducing human exposure help water monitor lizards maintain a microbiota similar to that in the wild environment.

scholarly journals Gut Microbiome Analysis As A Non-Invasive Tool for the Early Diagnosis of Cholangiocarcinoma

2021 ◽  
Author(s):  
Jialiang Li ◽  
Xueyan Li ◽  
Sina Zhang ◽  
Chen Jin ◽  
Zixia Lin ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Microbial Community Composition ◽  
Intestinal Flora ◽  
Alpha Diversity ◽  
16S Rrna Gene Sequencing ◽  
Intestinal Microbiome ◽  
Rrna Gene ◽  
Non Invasive ◽  
Hepatobiliary Cancer

Abstract BACKGROUNDThe liver-microbiome axis is implicated in the pathogenesis of hepatobiliary cancer, and the role of the gut microbiota in cholangiocarcinoma (CCA) remains unclear.METHODWe conducted a case-control study on the intestinal flora of 33 CCA patients and 47 cholelithiasis individuals. We performed 16S rRNA gene sequencing to identify disease-related gut microbiota and assess the potential of the intestinal microbiome as a non-invasive biomarker for CCA.RESULTWe found that gut microbiome of CCA patients had a significantly higher alpha diversity (Shannon and Observed species indices, p = 0.006 and p = 0.02, respectively) and an overall different microbial community composition (p = 0.032). The genus Muribaculaceae_unclassified was most strongly associated with CCA (p < 0.001). We put forward a disease predictive model including twelve intestinal microbiome genera distinguished CCA patients from CF patients with an area under curve (AUC) of approximately 0.93 (95%CI, 0.85–0.987). The forecasting performance of this model was better than CA19-9. Moreover, genera Ezakiella and Garciella were only observed among intrahepatic cholangiocarcinoma patients. Further, we assessed predicted functional modules alternations CCA patients and uncovered a microbiota pattern specific to CCA.CONCLUSIONOur findings provide evidence of the intestinal microbiome as a non-invasive biomarker for CCA.

scholarly journals The Devils Hole pupfish gut microbiome and its potential role in paradoxical anaerobism

2019 ◽  
Author(s):  
Shrikant S Bhute ◽  
Brisa Escobedo ◽  
Mina Haider ◽  
Yididya Mekonen ◽  
Dafhner Ferrer ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Microbial Communities ◽  
Critical Role ◽  
16S Rrna Gene Sequencing ◽  
Wide Distribution ◽  
Control Group ◽  
Rrna Gene ◽  
Dependent Manner ◽  
Bacterial Phyla ◽  
Devils Hole

Abstract Background The Devils Hole Pupfish ( Cyprinodon diabolis ) frequently enters paradoxical anaerobism in response to endogenously produced or exogenously supplied ethanol in a dose-dependent manner. To decipher the role of the gut microbiota in ethanol-associated paradoxical anaerobism, gut microbial communities were depleted using a cocktail of antibiotics and profiled using 16S rRNA gene sequencing. Results Compared to the control group (n=12), microbiota-depleted fish (n=11) spent more time in paradoxical anaerobism. Our analysis indicated that the bacterial phyla Proteobacteria , Fusobacteria , Bacteroidetes , Firmicutes , Actinobacteria , Patescibacteria , and Dependentiae dominated the pupfish gut, which is consistent with other fish gut microbiota. Although the gut microbial communities with and without antibiotic treatment were similarly diverse, they were distinct and the greatest contribution to the dissimilarity (27.38%) was the common fish commensal Cetobacterium . We speculate that Cetobacterium , a primary fermenter, also consumes ethanol through secondary fermentation via an alcohol dehydrogenase and therefore regulates the transition from paradoxical anaerobism to aerobic respiration in fish. Conclusions This study reports the first characterization of gut microbial communities of critically endangered pupfish and suggests the microbiome may play a critical role in regulating metabolic strategies that are critical for survival in extremes of temperature and oxygen concentration. Given the wide distribution and abundance of Cetobacterium in warm-water fishes, this process may be of broad importance, and suggests that the microbiome be carefully considered for both conservation and aquaculture.

scholarly journals Gut microbiota of patients with different subtypes of gastric cancer and gastrointestinal stromal tumors

Gut Pathogens ◽  
2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Virinder Sarhadi ◽  
Binu Mathew ◽  
Arto Kokkola ◽  
Tiina Karla ◽  
Milja Tikkanen ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gastric Adenocarcinoma ◽  
Gastrointestinal Stromal Tumors ◽  
Alpha Diversity ◽  
16S Rrna Gene Sequencing ◽  
Gastric Gist ◽  
Rrna Gene ◽  
Stromal Tumors ◽  
Gastric Tumors ◽  
Lower Abundance

Abstract Background Gastric adenocarcinoma is associated with H. pylori infection and inflammation that can result in the dysbiosis of gastric microbiota. The association of intestinal microbiota with gastric adenocarcinoma subtypes or with gastric gastrointestinal stromal tumors (GIST) is however not well known. Therefore, we performed 16S rRNA gene sequencing on DNA isolated from stool samples of Finnish patients and controls to study differences in microbiota among different histological subtypes of gastric adenocarcinoma, gastric GIST and healthy controls. Results We found that gut microbiota alpha diversity was lowest in diffuse adenocarcinoma patients, followed by intestinal type and GIST patients, although the differences were not significant compared to controls. Beta-diversity analysis however showed significant differences in microbiota composition for all subtypes compared to controls. Significantly higher abundance of Enterobacteriaceae was observed in both adenocarcinoma subtypes, whereas lower abundance of Bifidobacteriaceae was seen only in diffuse adenocarcinoma and of Oscillibacter in intestinal adenocarcinoma. Both GIST and adenocarcinoma patients had higher abundance of Enterobacteriaceae and lower abundance of Lactobacillaceae and Oscillibacter while lower abundance of Lachnoclostridium, Bifidobacterium, Parabacteroides and Barnesiella was seen only in the adenocarcinoma patients. Conclusions Our analysis shows association of higher Enterobacteriaceae abundance with all types of gastric tumors. Therefore it could be potentially useful as a marker of gastric malignancies. Lower gut microbiota diversity might be indicative of poorly differentiated, invasive, advanced or aggressive tumors and could possibly be a prognostic marker for gastric tumors.

scholarly journals Species-Level Gut Microbiota Analysis after Antibiotic-Induced Dysbiosis in Horses

Animals ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 2859
Author(s):  
Rebecca Di Pietro ◽  
Luis G. Arroyo ◽  
Mathilde Leclere ◽  
Marcio Carvalho Costa
Keyword(s):  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
Illumina Sequencing ◽  
Alpha Diversity ◽  
Species Level ◽  
Rrna Gene ◽  
Antibiotic Administration ◽  
Before And After ◽  
Long Read ◽  
Equine Studies

All current studies have used Illumina short-read sequencing to characterize the equine intestinal microbiota. Long-read sequencing can classify bacteria at the species level. The objectives of this study were to characterize the gut microbiota of horses at the species level before and after trimethoprim sulfadiazine (TMS) administration and to compare results with Illumina sequencing. Nine horses received TMS (30 mg/kg) orally for 5 days twice a day to induce dysbiosis. Illumina sequencing of the V4 region or full-length PacBio sequencing of the 16S rRNA gene was performed in fecal samples collected before and after antibiotic administration. The relative abundance and alpha diversity were compared between the two technologies. PacBio failed to classify the equine intestinal microbiota at the species level but confirmed Bacteroidetes as the most abundant bacteria in the feces of the studied horses, followed by Firmicutes and Fibrobacteres. An unknown species of the Bacteroidales order was highly abundant (13%) and deserves further investigation. In conclusion, PacBio was not suitable to classify the equine microbiota species but detected greater richness and less unclassified bacteria. Further efforts in improving current databanks to be used in equine studies are necessary.

Sign in / Sign up

Export Citation Format

Share Document