Multi-Omic Analysis Reveals Different Effects of Sulforaphane on the Microbiome and Metabolome in Old Compared to Young Mice

Dietary factors modulate interactions between the microbiome, metabolome, and immune system. Sulforaphane (SFN) exerts effects on aging, cancer prevention and reducing insulin resistance. This study investigated effects of SFN on the gut microbiome and metabolome in old mouse model compared with young mice. Young (6–8 weeks) and old (21–22 months) male C57BL/6J mice were provided regular rodent chow ± SFN for 2 months. We collected fecal samples before and after SFN administration and profiled the microbiome and metabolome. Multi-omics datasets were analyzed individually and integrated to investigate the relationship between SFN diet, the gut microbiome, and metabolome. The SFN diet restored the gut microbiome in old mice to mimic that in young mice, enriching bacteria known to be associated with an improved intestinal barrier function and the production of anti-inflammatory compounds. The tricarboxylic acid cycle decreased and amino acid metabolism-related pathways increased. Integration of multi-omic datasets revealed SFN diet-induced metabolite biomarkers in old mice associated principally with the genera, Oscillospira, Ruminococcus, and Allobaculum. Collectively, our results support a hypothesis that SFN diet exerts anti-aging effects in part by influencing the gut microbiome and metabolome. Modulating the gut microbiome by SFN may have the potential to promote healthier aging.

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Multi-omic analysis reveals the anti-aging impact of sulforaphane on the microbiome and metabolome

10.21203/rs.3.rs-43818/v1 ◽

2020 ◽

Author(s):

Jun Se-Ran ◽

Amrita Cheema ◽

Chhanda Bose ◽

Marjan Boerma ◽

Philip T Palade ◽

...

Keyword(s):

Gut Microbiome ◽

Tricarboxylic Acid Cycle ◽

Biological Effects ◽

Dietary Factors ◽

Cellular Respiration ◽

Aging Effects ◽

Metabolic Potential ◽

Fecal Samples ◽

Wide Range ◽

Old Mice

Abstract Background Dietary factors may modulate many complex interactions between the microbiome, metabolome, and immune system and can have an impact on the functional status of older adults. Sulforaphane (SFN), a natural compound and Nrf2-related activator of cytoprotective genes, provides a wide range of biological effects from cancer prevention to reducing insulin resistance. We have shown that SFN increased survival and improved cardiac and skeletal muscle function in a mouse model of aging. This study aims to investigate the anti-aging effects of SFN on the gut microbiome and metabolome.Results Young (6-8 weeks of age) and old (21-22 months of age) male C57BL/6J mice were provided regular rodent chow or chow containing SFN for 2 months. Fecal samples were collected right before and at the completion of SFN administration. We profiled the gut microbiome and applied global metabolomic profiling to fecal samples. Multi-omics datasets were analyzed individually and integrated to investigate the relationship between SFN diet, the microbiome, and metabolome. Microbial diversity, composition and functional capacity varied substantially across different age groups. On a global level, in old mice we observed that the SFN diet restored the gut microbiome to mimic that in young mice. In old mice, the SFN diet enriched bacteria associated with an improved intestinal barrier function and the production of anti-inflammatory compounds. In addition, the tricarboxylic acid cycle, central in cellular respiration, was decreased and amino acid metabolism-related pathways were increased. SFN diet induced metabolite biomarkers in old mice that are associated majorly with the genera, Oscillospira , Ruminococcus , and Allobaculum.Conclusion In old mice, SFN directed the metabolic potential to that of young animals. Integrated microbiome and metabolome analyses revealed metabolite biomarkers that could be modulated by bacteria and contribute to the anti-aging effects of SFN. Collectively, our results provide evidence in support of a novel hypothesis that SFN diet exerts anti-aging effects by influencing the gut microbiome and metabolome. Although further investigations are needed to identify precise mechanisms, modulating the gut microbiome by SFN may have the potential to promote healthier aging.

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The Role of Gut Microbiota in Intestinal Inflammation with Respect to Diet and Extrinsic Stressors

Microorganisms ◽

10.3390/microorganisms7080271 ◽

2019 ◽

Vol 7 (8) ◽

pp. 271 ◽

Cited By ~ 26

Author(s):

Stefani Lobionda ◽

Panida Sittipo ◽

Hyog Young Kwon ◽

Yun Kyung Lee

Keyword(s):

Gut Microbiota ◽

Intestinal Inflammation ◽

Intestinal Barrier ◽

Environmental Stressors ◽

Intestinal Barrier Function ◽

Symbiotic Relationship ◽

Inflammatory Bowel ◽

Host Metabolism ◽

The Relationship

The gut microbiota maintains a symbiotic relationship with the host and regulates several important functions including host metabolism, immunity, and intestinal barrier function. Intestinal inflammation and inflammatory bowel disease (IBD) are commonly associated with dysbiosis of the gut microbiota. Alterations in the gut microbiota and associated changes in metabolites as well as disruptions in the intestinal barrier are evidence of the relationship between the gut microbiota and intestinal inflammation. Recent studies have found that many factors may alter the gut microbiota, with the effects of diet being commonly-studied. Extrinsic stressors, including environmental stressors, antibiotic exposure, sleep disturbance, physical activity, and psychological stress, may also play important roles in altering the composition of the gut microbiota. Herein, we discuss the roles of the gut microbiota in intestinal inflammation in relation to diet and other extrinsic stressors.

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Bin1 Targeted Immunotherapy Alters the Status of the Enteric Neurons and the Microbiome during Ulcerative Colitis Treatment

10.20944/preprints202008.0643.v1 ◽

2020 ◽

Author(s):

Sunil Thomas ◽

Giancarlo Mercogliano ◽

George Prendergast

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiome ◽

Barrier Function ◽

Intestinal Barrier ◽

Enteric Neurons ◽

Intestinal Barrier Function ◽

Common Chronic Disease ◽

The Status ◽

Genus Lactobacillus ◽

High Level

Ulcerative colitis (UC) is a common chronic disease of the large intestine. Current anti-inflammatory drugs prescribed to treat this disease have limited utility due to significant side-effects. Thus, immunotherapies for UC treatment are still sought. In the DSS mouse model of UC, we recently demonstrated that systemic administration of the Bin1 monoclonal antibody 99D (Bin1 mAb) developed in our laboratory was sufficient to reinforce intestinal barrier function and preserve an intact colonic mucosa, compared to control subjects which displayed severe mucosal lesions, high-level neutrophil and lymphocyte infiltration of mucosal and submucosal areas, and loss of crypts. Here we report effects of Bin1 mAb on colonic neurons and the gut microbiome that correlate with the benefits of treatment. In the DSS model, we found that induction of UC was associated with disintegration of enteric neurons and elevated levels of glial cells, which translocated to the muscularis at distinct sites. Further, we characterized an altered gut microbiome in DSS treated mice associated with pathogenic proinflammatory characters. Both of these features of UC induction were normalized by Bin1 mAb treatment. With regard to microbiome changes, we observed in particular that Firmicutes were eliminated by UC induction and that Bin1 mAb treatment restored this phylum including the genus Lactobacillus and Akkermansia as beneficial microorganisms. Overall, our findings suggest that the intestinal barrier function restored by Bin1 immunotherapy in the DSS model of UC is associated with a preservation of enteric neurons and an improvement in the gut microbiome, contributing overall to a healthy intestinal tract.

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The High Incidence of Bacteremia in Children Undergoing Surgery Can Be Prevented by Bifidobacterium Supplementation

Annals of Nutrition and Metabolism ◽

10.1159/000479921 ◽

2017 ◽

Vol 71 (Suppl. 1) ◽

pp. 31-36 ◽

Cited By ~ 1

Author(s):

Tadaharu Okazaki ◽

Atsuyuki Yamataka ◽

Takashi Asahara ◽

Koji Nomoto ◽

Yuichiro Yamashiro

Keyword(s):

Randomized Controlled Trial ◽

Controlled Trial ◽

Health Benefit ◽

Intestinal Barrier ◽

Perioperative Period ◽

Intestinal Barrier Function ◽

Randomized Controlled ◽

High Incidence ◽

Patient At Risk ◽

The Relationship

Major surgical procedures can alter intestinal microbiota and disrupt the intestinal barrier function, leaving the patient at risk for infection. Probiotics are defined as live microorganisms that confer a health benefit on the host when administered in adequate amounts. Although the efficacy of administering probiotics perioperatively to adults has been reported, the clinical significance of probiotics in children undergoing surgery is still unclear. This study provides a brief overview of our randomized controlled trial of preoperative probiotic administration to children, and discusses the relationship between probiotics and their effects in the perioperative period, particularly focusing on bacteremia.

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Emerging Evidence on the Effects of Dietary Factors on the Gut Microbiome in Colorectal Cancer

10.20944/preprints202103.0712.v1 ◽

2021 ◽

Author(s):

Sandeep Appunni ◽

Muni Rubens ◽

Venkataraghavan Ramamoorthy ◽

Anshul Saxena ◽

Raees Tonse ◽

...

Keyword(s):

Colorectal Cancer ◽

Gut Microbiome ◽

Colonic Mucosa ◽

Fusobacterium Nucleatum ◽

Dietary Factors ◽

Lifestyle Modifications ◽

Related Factors ◽

Molecular Events ◽

Relationship Of ◽

The Relationship

Dietary factors play an important role in shaping the gut microbiome which, in turn, regulates the molecular events in colonic mucosa. The composition and resulting metabolism of the gut microbiome have been implicated in the development of colorectal cancer (CRC). Diets low in dietary fibers and phytomolecules as well as other lifestyle-related factors may predispose to CRC. Emerging evidence demonstrates that the predominance of microbes, such as Fusobacterium nucleatum, can predispose the colonic mucosa to malignant transformation. Dietary and lifestyle modifications have been demonstrated to restrict the growth of potentially harmful opportunistic organisms. In this study, we aim to present evidence regarding the relationship of dietary factors to the gut microbiome and development of CRC.

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Effects and Mechanisms of Probiotics, Prebiotics, Synbiotics, and Postbiotics on Metabolic Diseases Targeting Gut Microbiota: A Narrative Review

Nutrients ◽

10.3390/nu13093211 ◽

2021 ◽

Vol 13 (9) ◽

pp. 3211

Author(s):

Hang-Yu Li ◽

Dan-Dan Zhou ◽

Ren-You Gan ◽

Si-Yu Huang ◽

Cai-Ning Zhao ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gut Microbiota ◽

Metabolic Diseases ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Clinical Effects ◽

The One ◽

The Relationship ◽

Gut Microbiota Composition

Metabolic diseases are serious threats to public health and related to gut microbiota. Probiotics, prebiotics, synbiotics, and postbiotics (PPSP) are powerful regulators of gut microbiota, thus possessing prospects for preventing metabolic diseases. Therefore, the effects and mechanisms of PPSP on metabolic diseases targeting gut microbiota are worth discussing and clarifying. Generally, PPSP benefit metabolic diseases management, especially obesity and type 2 diabetes mellitus. The underlying gut microbial-related mechanisms are mainly the modulation of gut microbiota composition, regulation of gut microbial metabolites, and improvement of intestinal barrier function. Moreover, clinical trials showed the benefits of PPSP on patients with metabolic diseases, while the clinical strategies for gestational diabetes mellitus, optimal formula of synbiotics and health benefits of postbiotics need further study. This review fully summarizes the relationship between probiotics, prebiotics, synbiotics, postbiotics, and metabolic diseases, presents promising results and the one in dispute, and especially attention is paid to illustrates potential mechanisms and clinical effects, which could contribute to the next research and development of PPSP.

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Gut Microbiome and Its Associations With Acute and Chronic Gastrointestinal Toxicities in Cancer Patients With Pelvic Radiation Therapy: A Systematic Review

Frontiers in Oncology ◽

10.3389/fonc.2021.745262 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jinbing Bai ◽

Zahra A. Barandouzi ◽

Claire Rowcliffe ◽

Rebecca Meador ◽

Despina Tsementzi ◽

...

Keyword(s):

Systematic Review ◽

Radiation Therapy ◽

Gut Microbiome ◽

Assessment Tool ◽

Intestinal Barrier ◽

Included Study ◽

Radiation Enteritis ◽

Intestinal Barrier Function ◽

Screening Process ◽

Pelvic Radiation

AimPelvic radiation therapy (RT) can impact the gut microbiome in patients with cancer and result in gastrointestinal (GI) toxicities. The purpose of this systematic review was to describe the effects of RT on the gut microbiome and the associations between the gut microbiome and GI toxicities in patients treated with pelvic RT.MethodsPubMed, Embase, and Web of Science databases were searched from their earliest records to August 2020. The articles screening process adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Mixed Method Assessment Tool was used to assess the methodological quality for each included study. All study findings were synthesized and presented in narrative format. Thirteen studies were included. The gut microbiome of fecal samples was analyzed using 16S rRNA sequencing approaches.ResultsThere were disparities in alpha and beta diversities that existed across the studies. Divergent results were found among various phyla, including Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, Cyanobacteria, Fusobacteria, and Deinococcus-Thermus. Moreover, alteration in the gut microbiome diversity and abundance related to cancer treatment was associated with pelvic toxicities, specifically diarrhea. Following treatment, increases in the abundance of Bacteroides was associated with diarrhea and radiation enteritis.ConclusionsPelvic RT can disrupt the diversity and abundance of commensal gut microorganisms. A dysbiotic gut microbiome showed a promising association with radiation enteritis through alterations of the intestinal barrier function, innate immunity, and intestinal repair mechanisms; however, confounders, such as diet, were not thoroughly addressed.

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Linkage of gut microbiome with cognition in hepatic encephalopathy

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00190.2011 ◽

2012 ◽

Vol 302 (1) ◽

pp. G168-G175 ◽

Cited By ~ 260

Author(s):

Jasmohan S. Bajaj ◽

Jason M. Ridlon ◽

Phillip B. Hylemon ◽

Leroy R. Thacker ◽

Douglas M. Heuman ◽

...

Keyword(s):

Hepatic Encephalopathy ◽

Network Analysis ◽

Gut Microbiome ◽

Intestinal Barrier ◽

Fecal Microbiota ◽

Cognitive Testing ◽

Barrier Dysfunction ◽

Select Group ◽

Before And After ◽

End Stage

Hepatic encephalopathy (HE) has been related to gut bacteria and inflammation in the setting of intestinal barrier dysfunction. We aimed to link the gut microbiome with cognition and inflammation in HE using a systems biology approach. Multitag pyrosequencing (MTPS) was performed on stool of cirrhotics and age-matched controls. Cirrhotics with/without HE underwent cognitive testing, inflammatory cytokines, and endotoxin analysis. Patients with HE were compared with those without HE using a correlation-network analysis. A select group of patients with HE ( n = 7) on lactulose underwent stool MTPS before and after lactulose withdrawal over 14 days. Twenty-five patients [17 HE (all on lactulose, 6 also on rifaximin) and 8 without HE, age 56 ± 6 yr, model for end-stage liver disease score 16 ± 6] and ten controls were included. Fecal microbiota in cirrhotics were significantly different (higher Enterobacteriaceae , Alcaligeneceae , and Fusobacteriaceae and lower Ruminococcaceae and Lachnospiraceae ) compared with controls. We found altered flora (higher Veillonellaceae ), poor cognition, endotoxemia, and inflammation (IL-6, TNF-α, IL-2, and IL-13) in HE compared with cirrhotics without HE. In the cirrhosis group, Alcaligeneceae and Porphyromonadaceae were positively correlated with cognitive impairment. Fusobacteriaceae , Veillonellaceae , and Enterobacteriaceae were positively and Ruminococcaceae negatively related to inflammation. Network-analysis comparison showed robust correlations (all P < 1E-5) only in the HE group between the microbiome, cognition, and IL-23, IL-2, and IL-13. Lactulose withdrawal did not change the microbiome significantly beyond Fecalibacterium reduction. We concluded that cirrhosis, especially when complicated with HE, is associated with significant alterations in the stool microbiome compared with healthy individuals. Specific bacterial families ( Alcaligeneceae , Porphyromonadaceae , Enterobacteriaceae ) are strongly associated with cognition and inflammation in HE.

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Gut Microbiota-Mediated NLRP12 Expression Drives the Attenuation of Dextran Sulphate Sodium-Induced Ulcerative Colitis by Qingchang Wenzhong Decoction

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/9839474 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 2

Author(s):

Zhongmei Sun ◽

Wenjing Pei ◽

Yi Guo ◽

Zhibin Wang ◽

Rui Shi ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiota ◽

Clinical Symptoms ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Dextran Sulphate ◽

16S Rrna Analysis ◽

Dextran Sulphate Sodium ◽

Regulatory Effects ◽

The Relationship

Qingchang Wenzhong Decoction (QCWZD) is a newly developed, effective traditional Chinese herbal formulation for ulcerative colitis (UC). In earlier studies, we found that QCWZD could relieve the clinical symptoms of UC patients, reduce inflammation, and improve the intestinal barrier function in dextran sulphate sodium (DSS)-induced UC rats. However, the relationship between QCWZD and the gut microbiota in colitis was not clarified. In this study, we established a rat model of DSS-induced UC and then investigated the regulatory effects of QCWZD on the gut microbiota using 16S rRNA analysis. We also determined the expression of NLRP12 after QCWZD administration. Our findings suggested that QCWZD administration could modulate gut microbiota composition and selectively promote the protective strains such asButyricimonas,Blautia,andOdoribacter,whereas the enteric pathogens includingClostridiumandDoreawere significantly reduced after QCWZD treatment. It is noteworthy that QCWZD administration was identified to promote gut microbiota-mediated NLRP12 expression by inhibiting the activity of the TLR4/Blimp-1 axis. In conclusion, our study supports the potential of QCWZD administration as a beneficial therapeutic strategy for UC.

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Long-Term Blackcurrant Supplementation Modified Gut Microbiome Profiles in Mice in an Age-Dependent Manner: An Exploratory Study

Nutrients ◽

10.3390/nu12020290 ◽

2020 ◽

Vol 12 (2) ◽

pp. 290 ◽

Cited By ~ 1

Author(s):

Lei Cao ◽

Sang Gil Lee ◽

Melissa M. Melough ◽

Junichi R. Sakaki ◽

Kendra R. Maas ◽

...

Keyword(s):

Gut Microbiome ◽

Beta Diversity ◽

Age Groups ◽

Dependent Manner ◽

16S Sequencing ◽

Microbiome Composition ◽

Age Related ◽

Regulatory Effects ◽

Old Mice ◽

Young Mice

Recent studies have suggested that blackcurrant (BC) anthocyanins have promising health benefits, possibly through regulating gut microbiome. Three- and eighteen-month old female mice were fed standard mouse diets for 4 months, each with or without BC (1% w/w) supplementation (n = 3 in each treatment group, 12 in total). We then assessed gut microbiome profiles using 16S sequencing of their feces. Old mice had a less diverse microbiome community compared to young mice and there was a remarkable age-related difference in microbiome composition in the beta diversity analysis. BC supplementation did not significantly affect alpha or beta diversity. The relative abundance of several phyla, including Firmicutes, Bacteroidetes, Proteobacteria and Tenericutes, was lower in old mice. BC downregulated Firmicutes abundance in young mice and upregulated Bacteroidetes in both age groups, leading to a decreased Firmicutes/Bacteroidetes ratio. There were age-specific differences in the effect of BC supplementation on the microbiome. Twenty-four operational taxonomic units showed a significant interaction between age and BC supplementation (p < 0.01), which suggests that the ecosystem and the host health status affect the functions and efficiency of BC intake. These results indicate that BC supplementation favorably modulates gut microbiome, but there are distinct age-specific differences. Studies with human hosts are needed to better understand BC’s regulatory effects on the gut microbiome.

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