scholarly journals Adjunctive Probiotic Lactobacillus rhamnosus Probio-M9 Administration Enhances the Effect of Anti-PD-1 Antitumor Therapy via Restoring Antibiotic-Disrupted Gut Microbiota

2021 ◽  
Vol 12 ◽  
Author(s):  
Guangqi Gao ◽  
Teng Ma ◽  
Tao Zhang ◽  
Hao Jin ◽  
Yalin Li ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Lactobacillus Rhamnosus ◽  
Immune Checkpoint Blockade ◽  
Adjunctive Treatment ◽  
Potential Candidate ◽  
Antitumor Therapy ◽  
Amino Acid Synthesis ◽  
Fecal Microbiome ◽  
Suppression Effect ◽  
Probiotic Treatment

Emerging evidence supports that the efficacy of immune checkpoint blockade (ICB) therapy is associated with the host’s gut microbiota, as prior antibiotic intake often leads to poor outcome and low responsiveness toward ICB treatment. Therefore, we hypothesized that the efficacy of ICB therapy like anti-programmed cell death protein-1 (PD-1) treatment required an intact host gut microbiota, and it was established that probiotics could enhance the recovery of gut microbiota disruption by external stimuli. Thus, the present study aimed to evaluate the effect of the probiotics, Lactobacillus rhamnosus Probio-M9, on recovering antibiotic-disrupted gut microbiota and its impact on the outcome of ICB therapy in tumor-bearing mice. We first disrupted the mouse microbiota by antibiotics and then remediated the gut microbiota by probiotics or naturally. Tumor transplantation was then performed, followed by anti-PD-1-based antitumor therapy. Changes in the fecal metagenomes and the tumor suppression effect were monitored during different stages of the experiment. Our results showed that Probio-M9 synergized with ICB therapy, significantly improving tumor inhibition compared with groups not receiving the probiotic treatment (P < 0.05 at most time points). The synergistic effect was accompanied by effective restoration of antibiotic-disrupted fecal microbiome that was characterized by a drastically reduced Shannon diversity value and shifted composition of dominating taxa. Moreover, probiotic administration significantly increased the relative abundance of beneficial bacteria (e.g., Bifidobacterium pseudolongum, Parabacteroides distasonis, and some Bacteroides species; 0.0001 < P < 0.05). The gut microbiome changes were accompanied by mild reshaping of the functional metagenomes characterized by enrichment in sugar degradation and vitamin and amino acid synthesis pathways. Collectively, this study supported that probiotic administration could enhance the efficacy and responsiveness of anti-PD-1-based immunotherapy, and Probio-M9 could be a potential candidate of microbe-based synergistic tumor therapeutics. The preclinical data obtained here would support the design of future human clinical trials for further consolidating the current findings and for safety assessment of probiotic adjunctive treatment in ICB therapy.

scholarly journals Anti-Inflammatory and Gut Microbiota Modulatory Effect of Lactobacillus rhamnosus Strain LDTM 7511 in a Dextran Sulfate Sodium-Induced Colitis Murine Model

2020 ◽  
Vol 8 (6) ◽  
pp. 845
Author(s):  
Soyoung Yeo ◽  
Hyunjoon Park ◽  
Eunsol Seo ◽  
Jihee Kim ◽  
Byoung Kook Kim ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Lactobacillus Rhamnosus ◽  
Probiotic Strain ◽  
Experimental Models ◽  
Unknown Etiology ◽  
Opposite Pattern ◽  
Beneficial Effects ◽  
Probiotic Treatment

Inflammatory bowel disease (IBD) is a group of conditions involving chronic relapsing-remitting inflammation of the gastrointestinal tract with an unknown etiology. Although the cause–effect relationship between gut microbiota and IBD has not been clearly established, emerging evidence from experimental models supports the idea that gut microbes play a fundamental role in the pathogenesis of IBD. As microbiome-based therapeutics for IBD, the beneficial effects of probiotics have been found in animal colitis models and IBD patients. In this study, based on the dextran sulfate sodium (DSS)-induced colitis mouse model, we investigated Lactobacillus rhamnosus strain LDTM 7511 originating from Korean infant feces as a putative probiotic strain for IBD. The strain LDTM 7511 not only alleviated the release of inflammatory mediators, but also induced the transition of gut microbiota from dysbiotic conditions, exhibiting the opposite pattern in the abundance of DSS colitis-associated bacterial taxa to the DSS group. Our findings suggest that the strain LDTM 7511 has the potential to be used as a probiotic treatment for IBD patients in comparison to L. rhamnosus GG (ATCC 53103), which has been frequently used for IBD studies.

scholarly journals Functional Dynamics of the Gut Microbiome in Elderly People during Probiotic Consumption

mBio ◽  
2015 ◽  
Vol 6 (2) ◽  
Author(s):  
Emiley A. Eloe-Fadrosh ◽  
Arthur Brady ◽  
Jonathan Crabtree ◽  
Elliott F. Drabek ◽  
Bing Ma ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Lactobacillus Rhamnosus ◽  
Probiotic Bacteria ◽  
Healthy Human ◽  
Content Type ◽  
Treatment Comparison ◽  
Functional Dynamics ◽  
Single Organism ◽  
Probiotic Treatment ◽  
The Impact

ABSTRACT A mechanistic understanding of the purported health benefits conferred by consumption of probiotic bacteria has been limited by our knowledge of the resident gut microbiota and its interaction with the host. Here, we detail the impact of a single-organism probiotic, Lactobacillus rhamnosus GG ATCC 53103 (LGG), on the structure and functional dynamics (gene expression) of the gut microbiota in a study of 12 healthy individuals, 65 to 80 years old. The analysis revealed that while the overall community composition was stable as assessed by 16S rRNA profiling, the transcriptional response of the gut microbiota was modulated by probiotic treatment. Comparison of transcriptional profiles based on taxonomic composition yielded three distinct transcriptome groups that displayed considerable differences in functional dynamics. The transcriptional profile of LGG in vivo was remarkably concordant across study subjects despite the considerable interindividual nature of the gut microbiota. However, we identified genes involved in flagellar motility, chemotaxis, and adhesion from Bifidobacterium and the dominant butyrate producers Roseburia and Eubacterium whose expression was increased during probiotic consumption, suggesting that LGG may promote interactions between key constituents of the microbiota and the host epithelium. These results provide evidence for the discrete functional effects imparted by a specific single-organism probiotic and challenge the prevailing notion that probiotics substantially modify the resident microbiota within nondiseased individuals in an appreciable fashion. IMPORTANCE Probiotic bacteria have been used for over a century to promote digestive health. Many individuals report that probiotics alleviate a number of digestive issues, yet little evidence links how probiotic microbes influence human health. Here, we show how the resident microbes that inhabit the healthy human gut respond to a probiotic. The well-studied probiotic Lactobacillus rhamnosus GG ATCC 53103 (LGG) was administered in a clinical trial, and a suite of measurements of the resident microbes were taken to evaluate potential changes over the course of probiotic consumption. We found that LGG transiently enriches for functions to potentially promote anti-inflammatory pathways in the resident microbes.

scholarly journals Lactobacillus rhamnosus HDB1258 modulates gut microbiota-mediated immune response in mice with or without lipopolysaccharide-induced systemic inflammation

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sang-Kap Han ◽  
Yeon-Jeong Shin ◽  
Dong-Yeon Lee ◽  
Kyung Min Kim ◽  
Seo-Jin Yang ◽  
...  
Keyword(s):  
Immune Response ◽  
Gut Microbiota ◽  
Oral Administration ◽  
Systemic Inflammation ◽  
Nk Cell ◽  
Lactobacillus Rhamnosus ◽  
Expression Ratio ◽  
Macrophage Phagocytosis ◽  
Tnf Α ◽  
Gut Microbiota Composition

Abstract Background Gut microbiota closely communicate in the immune system to maintain a balanced immune homeostasis in the gastrointestinal tract of the host. Oral administration of probiotics modulates gut microbiota composition. In the present study, we isolated Lactobacillus rhamnosus HDB1258, which induced tumor necrosis factor (TNF)-α and interleukin (IL)-10 expression in macrophages, from the feces of breastfeeding infants and examined how HDB1258 could regulate the homeostatic immune response in mice with or without lipopolysaccharide (LPS)-induced systemic inflammation. Results Oral administration of HDB1258 significantly increased splenic NK cell cytotoxicity, peritoneal macrophage phagocytosis, splenic and colonic TNF-α expression, TNF-α to IL-10 expression ratio, and fecal IgA level in control mice, while Th1 and Treg cell differentiation was not affected in the spleen. However, HDB1258 treatment significantly suppressed peritoneal macrophage phagocytosis and blood prostaglandin E2 level in mice with LPS-induced systemic inflammation. Its treatment increased LPS-suppressed ratios of Treg to Th1 cell population, Foxp3 to T-bet expression, and IL-10 to TNF-α expression. Oral administration of HDB1258 significantly decreased LPS-induced colon shortening, myeloperoxidase activity and NF-κB+/CD11c+ cell population in the colon, while the ratio of IL-10 to TNF-α expression increased. Moreover, HDB1258 treatment shifted gut microbiota composition in mice with and without LPS-induced systemic inflammation: it increased the Cyanobacteria and PAC000664_g (belonging to Bacteroidetes) populations and reduced Deferribacteres and EU622763_s group (belonging to Bacteroidetes) populations. In particular, PAC001066_g and PAC001072_s populations were negatively correlated with the ratio of IL-10 to TNF-α expression in the colon, while the PAC001070_s group population was positively correlated. Conclusions Oral administered HDB1258 may enhance the immune response by activating innate immunity including to macrophage phagocytosis and NK cell cytotoxicity in the healthy host and suppress systemic inflammation in the host with inflammation by the modulation of gut microbiota and IL-10 to TNF-α expression ratio in immune cells.

Fermented carrot juice attenuates type 2 diabetes by mediating gut microbiota in rats

2019 ◽  
Vol 10 (5) ◽  
pp. 2935-2946 ◽  
Author(s):  
Rongkang Hu ◽  
Feng Zeng ◽  
Linxiu Wu ◽  
Xuzhi Wan ◽  
Yongfang Chen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acid ◽  
Gut Microbiota ◽  
Short Chain Fatty Acid ◽  
Lactobacillus Rhamnosus ◽  
Chain Fatty Acid ◽  
Carrot Juice ◽  
Protein Expressions ◽  
Free Phenolics

Carrot juice fermented with Lactobacillus rhamnosus GG, enriched with free phenolics, organic acids and short-chain fatty acid, has the potential to ameliorate type 2 diabetes, in part through modulating specific gut microbiota and regulating the mRNA and protein expressions levels involved in glucose metabolism.

scholarly journals Gut microbiota differs between children with Inflammatory Bowel Disease and healthy siblings in taxonomic and functional composition: a metagenomic analysis

2017 ◽  
Vol 312 (4) ◽  
pp. G327-G339 ◽  
Author(s):  
Rebecca L. Knoll ◽  
Kristoffer Forslund ◽  
Jens Roat Kultima ◽  
Claudius U. Meyer ◽  
Ulrike Kullmer ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Gut Microbiota ◽  
Bowel Disease ◽  
Virulence Genes ◽  
Metagenomic Sequencing ◽  
Fecal Microbiome ◽  
Microbial Dysbiosis ◽  
Healthy Siblings ◽  
Inflammatory Bowel ◽  
Sibling Study

Current treatment for pediatric inflammatory bowel disease (IBD) patients is often ineffective, with serious side effects. Manipulating the gut microbiota via fecal microbiota transplantation (FMT) is an emerging treatment approach but remains controversial. We aimed to assess the composition of the fecal microbiome through a comparison of pediatric IBD patients to their healthy siblings, evaluating risks and prospects for FMT in this setting. A case-control (sibling) study was conducted analyzing fecal samples of six children with Crohn’s disease (CD), six children with ulcerative colitis (UC) and 12 healthy siblings by metagenomic sequencing. In addition, lifetime antibiotic intake was retrospectively determined. Species richness and diversity were significantly reduced in UC patients compared with control [Mann-Whitney U-test false discovery rate (MWU FDR) = 0.011]. In UC, bacteria positively influencing gut homeostasis, e.g., Eubacterium rectale and Faecalibacterium prausnitzii, were significantly reduced in abundance (MWU FDR = 0.05). Known pathobionts like Escherichia coli were enriched in UC patients (MWU FDR = 0.084). Moreover, E. coli abundance correlated positively with that of several virulence genes (SCC > 0.65, FDR < 0.1). A shift toward antibiotic-resistant taxa in both IBD groups distinguished them from controls [MWU Benjamini-Hochberg-Yekutieli procedure (BY) FDR = 0.062 in UC, MWU BY FDR = 0.019 in CD). The collected results confirm a microbial dysbiosis in pediatric UC, and to a lesser extent in CD patients, replicating associations found previously using different methods. Taken together, these observations suggest microbiotal remodeling therapy from family donors, at least for children with UC, as a viable option. NEW & NOTEWORTHY In this sibling study, prior reports of microbial dysbiosis in IBD patients from 16S rRNA sequencing was verified using deep shotgun sequencing and augmented with insights into the abundance of bacterial virulence genes and bacterial antibiotic resistance determinants, seen against the background of data on the specific antibiotic intake of each of the study participants. The observed dysbiosis, which distinguishes patients from siblings, highlights such siblings as potential donors for microbiotal remodeling therapy in IBD.

Fecal Microbiome and Bile Acid Metabolome in Adult Short Bowel Syndrome

2021 ◽  
Author(s):  
Harold J. Boutte ◽  
Jacqueline Chen ◽  
Todd N. Wylie ◽  
Kristine M. Wylie ◽  
Yan Xie ◽  
...  
Keyword(s):  
Bile Acid ◽  
Gut Microbiota ◽  
Short Bowel Syndrome ◽  
Lithocholic Acid ◽  
Intestinal Failure ◽  
Patient Specific ◽  
Rrna Gene ◽  
Healthy Controls ◽  
Fecal Microbiome ◽  
Short Bowel

Background & Aims: Loss of functional small bowel surface area causes short bowel syndrome (SBS), intestinal failure, and parenteral nutrition (PN) dependence. The gut adaptive response following resection may be difficult to predict, and it may take up to two years to determine which patients will wean from PN. Here we examined features of gut microbiota and bile acid (BA) metabolism in determining adaptation and ability to wean from PN. Methods: Stool and sera were collected from healthy controls and from SBS patients (n=52) with ileostomy, jejunostomy, ileocolonic and jejunocolonic anastomoses fed with PN plus enteral nutrition or who were exclusively enterally fed. We undertook 16S rRNA gene sequencing, BA profiling and 7α-hydroxy-4-cholesten-3-one (C4) quantitation with LC-MS/MS, and serum amino acid analyses. Results: SBS patients exhibited altered gut microbiota with reduced gut microbial diversity compared to healthy controls. We observed differences in the microbiomes of SBS patients with ileostomy vs. jejunostomy, jejunocolonic vs. ileocolonic anastomoses, and PN-dependence compared to those who weaned from PN. Stool and serum BA composition and C4 concentrations were also altered in SBS patients, reflecting adaptive changes in enterohepatic BA cycling. Stools from patients who weaned from PN were enriched in secondary BAs including deoxycholic acid and lithocholic acid. Conclusions: Shifts in gut microbiota and BA metabolites may generate a favorable luminal environment in select SBS patients, promoting the ability to wean from PN. Pro-adaptive microbial species and select BA may provide novel targets for patient-specific therapies for SBS.

scholarly journals Citrus polymethoxyflavones attenuate metabolic syndrome by regulating gut microbiome and amino acid metabolism

2020 ◽  
Vol 6 (1) ◽  
pp. eaax6208 ◽  
Author(s):  
Su-Ling Zeng ◽  
Shang-Zhen Li ◽  
Ping-Ting Xiao ◽  
Yuan-Yuan Cai ◽  
Chu Chu ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Amino Acid ◽  
Gut Microbiota ◽  
Metabolic Diseases ◽  
Amplicon Sequencing ◽  
Therapeutic Interventions ◽  
Protective Effects ◽  
Fecal Microbiome ◽  
Metabolomic Profiling ◽  
Branched Chain

Metabolic syndrome (MetS) is intricately linked to dysregulation of gut microbiota and host metabolomes. Here, we first find that a purified citrus polymethoxyflavone-rich extract (PMFE) potently ameliorates high-fat diet (HFD)–induced MetS, alleviates gut dysbiosis, and regulates branched-chain amino acid (BCAA) metabolism using 16S rDNA amplicon sequencing and metabolomic profiling. The metabolic protective effects of PMFE are gut microbiota dependent, as demonstrated by antibiotic treatment and fecal microbiome transplantation (FMT). The modulation of gut microbiota altered BCAA levels in the host serum and feces, which were significantly associated with metabolic features and actively responsive to therapeutic interventions with PMFE. Notably, PMFE greatly enriched the commensal bacterium Bacteroides ovatus, and gavage with B. ovatus reduced BCAA concentrations and alleviated MetS in HFD mice. PMFE may be used as a prebiotic agent to attenuate MetS, and target-specific microbial species may have unique therapeutic promise for metabolic diseases.

scholarly journals Enterococcus faecium are associated with the modification of gut microbiota and shrimp post-larvae survival

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Shicong Du ◽  
Wei Chen ◽  
Zhiyuan Yao ◽  
Xiaolin Huang ◽  
Chen Chen ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Enterococcus Faecium ◽  
Path Model ◽  
Probiotic Bacteria ◽  
Rrna Gene ◽  
Phylogenetic Distance ◽  
Survival Ratio ◽  
Probiotic Treatment ◽  
Predicted Function

Abstract Background Probiotics are widely used to promote host health. Compared to mammals and terrestrial invertebrates, little is known the role of probiotics in aquatic invertebrates. In this study, eighteen tanks with eight hundred of shrimp post-larvae individuals each were randomly grouped into three groups, one is shrimps administered with E. faecium as probiotic (Tre) and others are shrimps without probiotic-treatment (CK1: blank control, CK2: medium control). We investigated the correlations between a kind of commercial Enterococcus faecium (E. faecium) powder and microbiota composition with function potentials in shrimp post-larvae gut. Results We sequenced the 16S rRNA gene (V4) of gut samples to assess diversity and composition of the shrimp gut microbiome and used differential abundance and Tax4Fun2 analyses to identify the differences of taxonomy and predicted function between different treatment groups. The ingested probiotic bacteria (E. faecium) were tracked in gut microbiota of Tre and the shrimps here showed the best growth performance especially in survival ratio (SR). The distribution of SR across samples was similar to that in PCoA plot based on Bray-Curits and two subgroups generated (SL: SR < 70%, SH: SR ≥ 70%). The gut microbiota structure and predicted function were correlated with both treatment and SR, and SR was a far more important factor driving taxonomic and functional differences than treatment. Both Tre and SH showed a low and uneven community species and shorted phylogenetic distance. We detected a shift in composition profile at phylum and genus level and further identified ten OTUs as relevant taxa that both closely associated with treatment and SR. The partial least squares path model further supported the important role of relevant taxa related to shrimp survival ratio. Conclusions Overall, we found gut microbiota correlated to both shrimp survival and ingested probiotic bacteria (E. faecium). These correlations should not be dismissed without merit and will uncover a promising strategy for developing novel probiotics through certain consortium of gut microbiota.

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