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 ◽  
...  

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.

2020 ◽  
Author(s):  
Bokyoung Lee ◽  
Jieun Lee ◽  
Min-Yeong Woo ◽  
Mi Jin Lee ◽  
Ho-Joon Shin ◽  
...  

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.


2020 ◽  
Vol 8 (9) ◽  
pp. 1376
Author(s):  
Zhenting Zhang ◽  
Jiali Liu ◽  
Xuexia Jin ◽  
Chao Liu ◽  
Chenwei Fan ◽  
...  

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.


PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250075
Author(s):  
Jian Ran ◽  
Qiu-Hong Wan ◽  
Sheng-Guo Fang

Gut microbiota is known to influence the host’s health; an imbalance of the gut microbial community leads to various intestinal and non-intestinal diseases. Research on gut microbes of endangered birds is vital for their conservation. However, a thorough understanding of the gut microbiome composition present in crested ibises at different ages and its correlation with crested ibis reproductive capacity has remained elusive. Here, we used 16S rRNA gene sequencing to explore the fecal microbial structure of nestlings and adult birds, and the difference in gut microbiota between healthy and sterile crested ibises. We observed that (1) bacterial microbiota, alpha and beta diversity of one-day-old nestlings significantly distinguished from other nestlings; abundance of Proteobacteria decreased, while that of Fusobacteria increased with an increase in the age of the nestlings; (2) there was no significant difference in community composition among adult crested ibises aged one, two, three, and five years; (3) the abundance of Proteobacteria and alpha diversity indices were higher in sterile crested ibises than in healthy crested ibises; thus, Proteobacteria can act as a diagnostic biomarker of reproductive dysfunction in crested ibises. This study significantly contributes to the field of ecology and conservation, as it provides a platform for assessing the reproductive capacity of endangered crested ibises, based on the gut microbiota composition. Further studies may unravel additional factors influencing crested ibises’ reproductive health, which will further help the management and control of the crested ibis population.


2021 ◽  
Vol 9 (5) ◽  
pp. 1037
Author(s):  
Craig Resch ◽  
Mihir Parikh ◽  
J. Alejandro Austria ◽  
Spencer D. Proctor ◽  
Thomas Netticadan ◽  
...  

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.


Author(s):  
Yoshihiro Tomizawa ◽  
Shunya Kurokawa ◽  
Daiki Ishii ◽  
Katsuma Miyaho ◽  
Chiharu Ishii ◽  
...  

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.


Animals ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 2125
Author(s):  
Limin Wei ◽  
Bo Zeng ◽  
Siyuan Zhang ◽  
Feng Li ◽  
Fanli Kong ◽  
...  

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.


2022 ◽  
Vol 12 ◽  
Author(s):  
Yu Du ◽  
Jun-Qiong Chen ◽  
Qian Liu ◽  
Jian-Chao Fu ◽  
Chi-Xian Lin ◽  
...  

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.


2021 ◽  
Author(s):  
Artur Trzebny ◽  
Anna Slodkowicz-Kowalska ◽  
Johanna Björkroth ◽  
Miroslawa Dabert

AbstractThe animal gut microbiota consist of many different microorganisms, mainly bacteria, but archaea, fungi, protozoans, and viruses may also be present. This complex and dynamic community of microorganisms may change during parasitic infection. In the present study, we investigated the effect of the presence of microsporidians on the composition of the mosquito gut microbiota and linked some microbiome taxa and functionalities to infections caused by these parasites. We characterised bacterial communities of 188 mosquito females, of which 108 were positive for microsporidian DNA. To assess how bacterial communities change during microsporidian infection, microbiome structures were identified using 16S rRNA microbial profiling. In total, we identified 46 families and four higher taxa, of which Comamonadaceae, Enterobacteriaceae, Flavobacteriaceae and Pseudomonadaceae were the most abundant mosquito-associated bacterial families. Our data suggest that the mosquito gut microbial composition varies among host species. In addition, we found a correlation between the microbiome composition and the presence of microsporidians. The prediction of metagenome functional content from the 16S rRNA gene sequencing suggests that microsporidian infection is characterised by some bacterial species capable of specific metabolic functions, especially the biosynthesis of ansamycins and vancomycin antibiotics and the pentose phosphate pathway. Moreover, we detected a positive correlation between the presence of microsporidian DNA and bacteria belonging to Spiroplasmataceae and Leuconostocaceae, each represented by a single species, Spiroplasma sp. PL03 and Weissella cf. viridescens, respectively. Additionally, W. cf. viridescens was observed only in microsporidian-infected mosquitoes. More extensive research, including intensive and varied host sampling, as well as determination of metabolic activities based on quantitative methods, should be carried out to confirm our results.


2019 ◽  
Vol 50 (1) ◽  
Author(s):  
Meera Surendran Nair ◽  
Tyson Eucker ◽  
Brian Martinson ◽  
Axel Neubauer ◽  
Joseph Victoria ◽  
...  

Abstract This study investigated the influence of gut microbiome composition in modulating susceptibility to Mycoplasma hyopneumoniae in pigs. Thirty-two conventional M. hyopneumoniae free piglets were randomly selected from six different litters at 3 weeks of age and were experimentally inoculated with M. hyopneumoniae at 8 weeks of age. Lung lesion scores (LS) were recorded 4 weeks post-inoculation (12 weeks of age) from piglet lungs at necropsy. Fecal bacterial community composition of piglets at 3, 8 and 12 weeks of age were targeted by amplifying the V3–V4 region of the 16S rRNA gene. The LS ranged from 0.3 to 43% with an evident clustering of the scores observed in piglets within litters. There were significant differences in species richness and alpha diversity in fecal microbiomes among piglets within litters at different time points (p < 0.05). The dissimilarity matrices indicated that at 3 weeks of age, the fecal microbiota of piglets was more dissimilar compared to those from 8 to 12 weeks of age. Specific groups of bacteria in the gut that might predict the decreased severity of M. hyopneumoniae associated lesions were identified. The microbial shift at 3 weeks of age was observed to be driven by the increase in abundance of the indicator family, Ruminococcaceae in piglets with low LS (p < 0.05). The taxa, Ruminococcus_2 having the highest richness scores, correlated significantly between litters showing stronger associations with the lowest LS (r = −0.49, p = 0.005). These findings suggest that early life gut microbiota can be a potential determinant for M. hyopneumoniae susceptibility in pigs.


Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2564 ◽  
Author(s):  
Iñaki Robles-Vera ◽  
María Callejo ◽  
Ricardo Ramos ◽  
Juan Duarte ◽  
Francisco Perez-Vizcaino

Inadequate immunologic, metabolic and cardiovascular homeostasis has been related to either an alteration of the gut microbiota or to vitamin D deficiency. We analyzed whether vitamin D deficiency alters rat gut microbiota. Male Wistar rats were fed a standard or a vitamin D-free diet for seven weeks. The microbiome composition was determined in fecal samples by 16S rRNA gene sequencing. The vitamin D-free diet produced mild changes on α- diversity but no effect on β-diversity in the global microbiome. Markers of gut dysbiosis like Firmicutes-to-Bacteroidetes ratio or the short chain fatty acid producing bacterial genera were not significantly affected by vitamin D deficiency. Notably, there was an increase in the relative abundance of the Enterobacteriaceae, with significant rises in its associated genera Escherichia, Candidatus blochmannia and Enterobacter in vitamin D deficient rats. Prevotella and Actinomyces were also increased and Odoribacteraceae and its genus Butyricimonas were decreased in rats with vitamin D-free diet. In conclusion, vitamin D deficit does not induce gut dysbiosis but produces some specific changes in bacterial taxa, which may play a pathophysiological role in the immunologic dysregulation associated with this hypovitaminosis.


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