A Novel Probiotic Formula, BIOCG, Protects Against Alzheimer’s-Related Cognitive Deficits via Regulation of Dendritic Spine Dynamics

2021 ◽  
Vol 18 ◽  
Author(s):  
Miao Sun ◽  
Wenchenyang Bao ◽  
Chengyu Huang ◽  
Ziyue Xia ◽  
Changliang Zhang ◽  
...  
Keyword(s):  
Dendritic Spine ◽  
Gut Microbiome ◽  
Long Term Potentiation ◽  
Functional Improvement ◽  
Sequencing Data ◽  
Microbial Composition ◽  
App Processing ◽  
Probiotic Treatment ◽  
The Impact ◽  
Spine Dynamics

Background: The brain-gut-microbiome axis has emerged as an important pathway through which perturbations in the gut and/or microbial microenvironment can impact neurological function. Such alterations have been implicated in a variety of neuropsychiatric disorders, includ- ing depression, anxiety, and Alzheimer’s Disease (AD) and the use of probiotics as therapy for th- ese diseases remains promising. However, the mechanisms underlying the gut microenvironment’s influence on disease pathogenesis and therapy remain unclear. Objective: The objective of this study is to investigate the effect of a novel probiotic formula, BIOCG, on cognitive function and pathobiological mechanisms, including amyloid processing and dendritic spine dynamics, in a mouse model of AD. Methods: BIOCG was administered for 3 months to 3xTg or 3xTg; Thy1-YFP AD mice and func- tional outcomes were assessed via behavioral testing and electrophysiology. Mechanisms relevant to AD pathogenesis including dendritic spine morphology and turnover, Amyloid Precursor Pro- tein (APP) processing and microglial phenotype were also evaluated. Finally, we sequenced fecal samples following probiotic treatment to assess the impact on gut microbial composition and corre- late the changes with the above described measures. Results: Mice treated with BIOCG demonstrated preserved cognitive abilities and stronger Long- Term Potentiation (LTP), spontaneous Excitatory Postsynaptic Currents (sEPSC), and glutamate-in- duced LTPs, indicative of functional and electrophysiological effects. Moreover, we observed atten- uated AD pathogenesis, including reduced Amyloid Beta (Aβ) burden, as well as more mature den- dritic spines in the BIOCG-treated. Our finding of changes in microglial number and phenotype in the treatment group suggests that this formulation may mediate its effects via attenuation of neu- roinflammation. Sequencing data confirmed that the gut microbiome in treated mice was more varied and harbored a greater proportion of “beneficial” bacteria. Conclusion: Overall, our results indicate that treatment with BIOCG enhances microbial diversity and, through gut-brain axis interactions, attenuates neuroinflammation to produce histologic and functional improvement in AD pathogenesis.

IMMU-09. HUMAN MICROBIOTA INFLUENCE THE EFFICACY OF IMMUNOTHERAPY IN A MOUSE MODEL OF GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi93-vi94
Author(s):  
Kory Dees ◽  
Hyunmin Koo ◽  
James Humphreys ◽  
Joseph Hakim ◽  
David Crossman ◽  
...  
Keyword(s):  
Mouse Model ◽  
Microbial Communities ◽  
Mouse Models ◽  
Gut Microbiome ◽  
Positive Response ◽  
Checkpoint Inhibitors ◽  
Metagenomic Sequencing ◽  
Sequencing Data ◽  
Microbial Composition ◽  
Healthy Human

Abstract Although immunotherapy works well in glioblastoma (GBM) pre-clinical mouse models, the therapy has unfortunately not demonstrated efficacy in humans. In melanoma and other cancers, the composition of the gut microbiome has been shown to determine responsiveness or resistance to immune checkpoint inhibitors (anti-PD-1). Most pre-clinical cancer studies have been done in mouse models using mouse gut microbiomes, but there are significant differences between mouse and human microbial gut compositions. To address this inconsistency, we developed a novel humanized microbiome (HuM) model to study the response to immunotherapy in a pre-clinical mouse model of GBM. We used five healthy human donors for fecal transplantation of gnotobiotic mice. After the transplanted microbiomes stabilized, the mice were bred to generate five independent humanized mouse lines (HuM1-HuM5). Analysis of shotgun metagenomic sequencing data from fecal samples revealed a unique microbiome with significant differences in diversity and microbial composition among HuM1-HuM5 lines. Interestingly, we found that the HuM lines responded differently to anti-PD-1. Specifically, we demonstrate that HuM2 and HuM3 mice are responsive to anti-PD-1 and displayed significantly increased survival compared to isotype controls, while HuM1, HuM4, and HuM5 mice are resistant to anti-PD-1. These mice are genetically identical, and only differ in the composition of the gut microbiome. In a correlative experiment, we found that disrupting the responder HuM2 microbiome with antibiotics abrogated the positive response to anti-PD-1, indicating that HuM2 microbiota must be present in the mice to elicit the positive response to anti-PD-1 in the GBM model. The question remains of whether the “responsive” microbial communities in HuM2 and HuM3 can be therapeutically exploited and applicable in other tumor models, or if the “resistant” microbial communities in HuM1, HuM4, and HuM5 can be depleted and/or replaced. Future studies will assess responder microbial transplants as a method of enhancing immunotherapy.

scholarly journals The Impact of Environmental Chemicals on the Gut Microbiome

2020 ◽  
Vol 176 (2) ◽  
pp. 253-284 ◽  
Author(s):  
Karen Chiu ◽  
Genoa Warner ◽  
Romana A Nowak ◽  
Jodi A Flaws ◽  
Wenyan Mei
Keyword(s):  
Gut Microbiome ◽  
Current Knowledge ◽  
Environmental Chemicals ◽  
Microbial Composition ◽  
Multiple Factors ◽  
Microbiome Research ◽  
Health Related ◽  
Exogenous Factors ◽  
The Impact ◽  
Insight Into

Abstract Since the surge of microbiome research in the last decade, many studies have provided insight into the causes and consequences of changes in the gut microbiota. Among the multiple factors involved in regulating the microbiome, exogenous factors such as diet and environmental chemicals have been shown to alter the gut microbiome significantly. Although diet substantially contributes to changes in the gut microbiome, environmental chemicals are major contaminants in our food and are often overlooked. Herein, we summarize the current knowledge on major classes of environmental chemicals (bisphenols, phthalates, persistent organic pollutants, heavy metals, and pesticides) and their impact on the gut microbiome, which includes alterations in microbial composition, gene expression, function, and health effects in the host. We then discuss health-related implications of gut microbial changes, which include changes in metabolism, immunity, and neurological function.

scholarly journals Microbiability of meat quality and carcass composition traits in swine

2020 ◽  
Author(s):  
Piush Khanal ◽  
Christian Maltecca ◽  
Clint Schwab ◽  
Justin Fix ◽  
Francesco Tiezzi
Keyword(s):  
Meat Quality ◽  
Gut Microbiome ◽  
Complex Traits ◽  
Carcass Composition ◽  
Intestinal Microbiome ◽  
Quality Traits ◽  
Microbial Composition ◽  
Meat Quality Traits ◽  
Genomic Heritability ◽  
The Impact

Abstract BackgroundSwine gut microbiome constitutes a portion of the whole genome and has potential to affect different phenotypes. More recently, research is more directed towards association of gut microbiome and different traits in swine. However, the contribution of microbial composition to the phenotypic variation of meat quality and carcass composition traits in pigs has not been explored yet. The objectives of this study are to estimate the microbiabilities for different meat quality and carcass composition traits; to investigate the impact of intestinal microbiome on heritability estimates; to estimate the correlation between microbial diversity and meat quality and carcass composition traits; and to estimate the microbial correlation between the meat quality and carcass composition traits in a commercial swine population.ResultsThe contribution of the microbiome to carcass composition and meat quality traits was prominent although it varied over time, increasing from weaning to off test for most traits. Microbiability estimates of carcass composition traits were greater than that of meat quality traits. Among all of the traits analyzed, belly weight had higher microbiability estimate (0.29 ± 0.04). Adding microbiome information did not affect the estimates of genomic heritability of meat quality traits but affected the estimates of carcass composition traits. Fat depth had greater decrease (10%) in genomic heritability. High microbial correlations were found among several traits. This suggested that genomic correlation was partially contributed by genetic similarity of microbiome composition.ConclusionsResults indicate that better understanding of microbial composition could aid the improvement of complex traits, particularly the carcass composition traits in swine by inclusion of microbiome information in the genetic evaluation process.

scholarly journals Probiotics maintain the gut microbiome homeostasis during Indian Antarctic expedition by ship

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ashish Kumar Srivastava ◽  
Vishwajeet Rohil ◽  
Brij Bhushan ◽  
Malleswara Rao Eslavath ◽  
Harshita Gupta ◽  
...  
Keyword(s):  
Placebo Group ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Glycoside Hydrolases ◽  
Gut Health ◽  
Microbial Composition ◽  
Carbohydrate Binding Modules ◽  
Antarctic Expedition ◽  
Probiotic Intervention ◽  
The Impact

AbstractShip voyage to Antarctica is a stressful journey for expedition members. The response of human gut microbiota to ship voyage and a feasible approach to maintain gut health, is still unexplored. The present findings describe a 24-day long longitudinal study involving 19 members from 38th Indian Antarctic Expedition, to investigate the impact of ship voyage and effect of probiotic intervention on gut microbiota. Fecal samples collected on day 0 as baseline and at the end of ship voyage (day 24), were analyzed using whole genome shotgun sequencing. Probiotic intervention reduced the sea sickness by 10% compared to 44% in placebo group. The gut microbiome in placebo group members on day 0 and day 24, indicated significant alteration compared to a marginal change in the microbial composition in probiotic group. Functional analysis revealed significant alterations in carbohydrate and amino acid metabolism. Carbohydrate-active enzymes analysis represented functional genes involved in glycoside hydrolases, glycosyltransferases and carbohydrate binding modules, for maintaining gut microbiome homeostasis. Suggesting thereby the possible mechanism of probiotic in stabilizing and restoring gut microflora during stressful ship journey. The present study is first of its kind, providing a feasible approach for protecting gut health during Antarctic expedition involving ship voyage.

scholarly journals Infants’ First Solid Foods: Impact on Gut Microbiota Development in Two Intercontinental Cohorts

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2639
Author(s):  
Chiara-Maria Homann ◽  
Connor A. J. Rossel ◽  
Sara Dizzell ◽  
Liene Bervoets ◽  
Julia Simioni ◽  
...  
Keyword(s):  
Community Structure ◽  
Gut Microbiome ◽  
Dietary Diversity ◽  
Solid Food ◽  
Microbial Composition ◽  
Term Infants ◽  
Negatively Associated ◽  
Solid Foods ◽  
Solid Food Introduction ◽  
The Impact

The introduction of solid foods is an important dietary event during infancy that causes profound shifts in the gut microbial composition towards a more adult-like state. Infant gut bacterial dynamics, especially in relation to nutritional intake remain understudied. Over 2 weeks surrounding the time of solid food introduction, the day-to-day dynamics in the gut microbiomes of 24 healthy, full-term infants from the Baby, Food & Mi and LucKi-Gut cohort studies were investigated in relation to their dietary intake. Microbial richness (observed species) and diversity (Shannon index) increased over time and were positively associated with dietary diversity. Microbial community structure (Bray–Curtis dissimilarity) was determined predominantly by individual and age (days). The extent of change in community structure in the introductory period was negatively associated with daily dietary diversity. High daily dietary diversity stabilized the gut microbiome. Bifidobacterial taxa were positively associated, while taxa of the genus Veillonella, that may be the same species, were negatively associated with dietary diversity in both cohorts. This study furthers our understanding of the impact of solid food introduction on gut microbiome development in early life. Dietary diversity seems to have the greatest impact on the gut microbiome as solids are introduced.

scholarly journals Effect of radiotherapy on the gut microbiome in pediatric cancer patients: a pilot study

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7683 ◽  
Author(s):  
Nourhan Sahly ◽  
Ahmed Moustafa ◽  
Mohamed Zaghloul ◽  
Tamer Z. Salem
Keyword(s):  
Pilot Study ◽  
Sample Size ◽  
Cancer Patients ◽  
Pediatric Cancer ◽  
Gut Microbiome ◽  
Small Sample ◽  
Response To Treatment ◽  
Microbial Composition ◽  
Pediatric Cancer Patients ◽  
The Impact

The incidence of pediatric cancer is lower than that of adult cancer worldwide. However, the former has detrimental side effects on the health of individuals, even after the cancer is cured, due to the impact of treatment on development. Recently, correlations have been made between the gut microbiome and cancer in several studies but only on adult participants. There is always a complication of dealing with pediatric cancer treatment protocols because they usually include a combination of chemotherapy, radiotherapy, and intensive prophylactic antibiotics. In the current study, a pilot study was conducted to analyze ten fecal samples from three pediatric cancer patients, suffering from rhabdomyosarcoma near their pelvic region, and two healthy individuals. A correlation between microbial composition and response to treatment was reported, in which the responders had generally a lower microbial diversity compared to non-responders. In addition, nucleotide changes and deletions in the tested 16S rRNA sequences post radiotherapy were detected. Despite the small sample size used in the experiments due to the uncommon rhabdomyosarcoma in children, the results can help in understanding the influence of radiotherapy on the gut microbiome in pediatric cancer patients. More work with larger sample size and different cancer types need to be conducted to understand the influence of radiotherapy on gut microbiome to mitigate the deleterious impact of radiation on treated children.

Association between Gut Microbiome and Frailty in the Older Adult Population in Korea

2021 ◽  
Author(s):  
Mi Young Lim ◽  
Seungpyo Hong ◽  
Jung-Ha Kim ◽  
Young-Do Nam
Keyword(s):  
Older Adults ◽  
Gut Microbiome ◽  
Adult Population ◽  
Frailty Index ◽  
Depression Scale ◽  
Geriatric Syndrome ◽  
Rrna Gene ◽  
Sequencing Data ◽  
Microbial Composition ◽  
Increased Risk

Abstract Frailty is a common geriatric syndrome associated with the risk of adverse health outcomes. Recently, two key pathophysiological characteristics of frailty, altered energy metabolism and dysregulated immunity, have been reported to be associated with gut microbiome dysbiosis, indicating that the gut microbiome plays a role in frailty. However, few studies have directly examined the relationship between the gut microbiome and frailty. Here, we investigated the association of frailty measures with the gut microbiome using 16S rRNA gene sequencing data obtained from the fecal samples of 176 Korean older adults. Overall frailty was scored using the Korean Frailty Index (FI). Grip strength and Geriatric Depression Scale (GDS) scores were used as physical and mental frailty measures, respectively. In contrast to age, metabolic, and inflammatory biomarkers, the frailty measures were associated with inter-individual variations in microbial composition (false discovery rate [FDR] < 0.2). Both FI and GDS scores were negatively associated with microbial diversity (FDR < 0.2). Frailty measures showed distinct associations with specific microbial taxa and metabolic functions. Particularly, the Bacteroides enterotype was found only in subjects categorized in the frail group. Moreover, we observed that the abundance of beneficial taxa, such as Prevotella copri and Coprococcus eutactus, was reduced in frailer individuals, whereas that of detrimental taxa, such as Bacteroides fragilis and Clostridium hathewayi, was increased (FDR < 0.2). Our findings suggest that the gut microbiome can be used an indicator of an increased risk of frailty or a target for improving health in frail older adults.

scholarly journals The potential therapeutic effects of the gut microbiome manipulation by synbiotic containing-Lactobacillus plantarum on neuropsychological performance of diabetic rats

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Mohammad Morshedi ◽  
Maryam Saghafi-Asl ◽  
Elaheh-Sadat Hosseinifard
Keyword(s):  
Oxidative Stress ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Therapeutic Potential ◽  
Diabetic Rats ◽  
Therapeutic Effects ◽  
Microbial Composition ◽  
Stress Markers ◽  
Oxidative Stress Status ◽  
The Impact

Abstract Background The manipulation of gut microbiota as a target has been suggested to reduce the risks for a number of diseases such as type 2 diabetes mellitus (T2DM). Conversely, T2DM is associated with complications such as gut and brain disorders. Furthermore, the impact of probiotics and prebiotics to improve T2DM complications are reported. Thus, the present study seeks to investigate the therapeutic and neuropsychological effects of L. plantarum and inulin in diabetic rats. Methods Throughout the investigation, L. plantarum, inulin or their combination (synbiotic) was administered to diabetic rats. in the end, fecal samples were collected to evaluate the gut microbial composition. Then behavioral tests were conducted. Subsequently, the obtainment of the prefrontal cortex (PFC) and hippocampal samples. Results Our data demonstrated that administration of L. plantarum and inulin could improve gut dysbiosis and oxidative stress status. In addition, it could ameliorate serotonin and BDNF/TrkB signaling pathway. Notably, a strong correlation between the gut microbiota changes and cognition responses was observed. Interestingly, synbiotics intake exploited a rather powerful effect on oxidative stress markers. Conclusion The findings confirm that there is a beneficial therapeutic potential of supplements, especially symbiotic. Moreover, neuropsychological improvement associated with balanced gut microbiome.

scholarly journals The Impact of Anthelmintic Treatment on Human Gut Microbiota Based on Cross-Sectional and Pre- and Postdeworming Comparisons in Western Kenya

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Alice V. Easton ◽  
Mariam Quiñones ◽  
Ivan Vujkovic-Cvijin ◽  
Rita G. Oliveira ◽  
Stella Kepha ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Intestinal Parasites ◽  
Fold Change ◽  
Rrna Gene ◽  
Human Gut ◽  
Microbial Composition ◽  
Content Type ◽  
Average Fold Change ◽  
The Impact

ABSTRACT Murine studies suggest that the presence of some species of intestinal helminths is associated with changes in host microbiota composition and diversity. However, studies in humans have produced varied conclusions, and the impact appears to vary widely depending on the helminth species present. To demonstrate how molecular approaches to the human gut microbiome can provide insights into the complex interplay among disparate organisms, DNA was extracted from cryopreserved stools collected from residents of 5 rural Kenyan villages prior to and 3 weeks and 3 months following albendazole (ALB) therapy. Samples were analyzed by quantitative PCR (qPCR) for the presence of 8 species of intestinal parasites and by MiSeq 16S rRNA gene sequencing. Based on pretreatment results, the presence of neither Ascaris lumbricoides nor Necator americanus infection significantly altered the overall diversity of the microbiota in comparison with age-matched controls. Following ALB therapy and clearance of soil-transmitted helminths (STH), there were significant increases in the proportion of the microbiota made up by Clostridiales (P = 0.0002; average fold change, 0.57) and reductions in the proportion made up by Enterobacteriales (P = 0.0004; average fold change, −0.58). There was a significant posttreatment decrease in Chao1 richness, even among individuals who were uninfected pretreatment, suggesting that antimicrobial effects must be considered in any posttreatment setting. Nevertheless, the helminth-associated changes in Clostridiales and Enterobacteriales suggest that clearance of STH, and of N. americanus in particular, alters the gut microbiota. IMPORTANCE The gut microbiome is an important factor in human health. It is affected by what we eat, what medicines we take, and what infections we acquire. In turn, it affects the way we absorb nutrients and whether we have excessive intestinal inflammation. Intestinal worms may have an important impact on the composition of the gut microbiome. Without a complete understanding of the impact of mass deworming programs on the microbiome, it is impossible to accurately calculate the cost-effectiveness of such public health interventions and to guard against any possible deleterious side effects. Our research examines this question in a “real-world” setting, using a longitudinal cohort, in which individuals with and without worm infections are treated with deworming medication and followed up at both three weeks and three months posttreatment. We quantify the impact of roundworms and hookworms on gut microbial composition, suggesting that the impact is small, but that treatment of hookworm infection results in significant changes. This work points to the need for follow-up studies to further examine the impact of hookworm on the gut microbiota and determine the health consequences of the observed changes.

The impact of gut microbial composition on response to neoadjuvant chemotherapy (NACT) in early-stage triple negative breast cancer (TNBC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 590-590
Author(s):  
Nour Abuhadra ◽  
Chia-Chi Chang ◽  
Clinton Yam ◽  
Jason B White ◽  
Elizabeth Ravenberg ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Early Stage ◽  
Univariate Analysis ◽  
Alpha Diversity ◽  
Microbial Composition ◽  
Fecal Microbiota Transplant ◽  
Fecal Samples ◽  
Response To Chemotherapy ◽  
Significant Difference ◽  
The Impact

590 Background: The impact of gut microbiome on tumor biology, progression and response to immunotherapy has been shown across cancer types. However, there is little known about the impact of gut microbial composition on response to chemotherapy. We have previously shown that the gut microbiome remains unaltered during NACT in a cohort of 32 patients. Here we investigate the association between gut microbiome and response to NACT in a larger cohort of early-stage TNBC. Methods: Longitudinal fecal samples were collected from 85 patients with newly-diagnosed, early-stage TNBC patients enrolled in the ARTEMIS trial (NCT02276443). Patients all received standard NACT with adriamycin/cyclophosphamide (AC); volumetric change was assessed using ultrasound and patients with < 70% volumetric reduction (VR) after 4 cycles of AC were recommended to receive targeted therapy in addition to standard NACT to improve response rates. We performed 16S sequencing on bacterial genomic DNA extracted from 85 pre-AC fecal samples using the 2x250 bp paired-end read protocol. Quality-filtered sequences were clustered into Operational Taxonomic Units and classified using Mothur method with the Silva database version 138. For differential taxa-based univariate analysis, abundant microbiome taxa at species, genus, family, class, and order levels were analyzed using DESeq2 after logit transformation. Alpha-diversity indices within group categories were calculated using phyloseq. Microbial alpha diversity (within-sample diversity) was measured by Simpson's reciprocal index. β-diversity was measured using weighted UniFrac distances between the groups. The association between microbiota abundance and pathologic complete response (pCR) or residual disease (RD) was assessed using DESeq2 analysis. Results: Pre-AC fecal samples from 85 patients were available for analysis. Amongst them, there were 46 patients with pCR and 39 patients with RD. There was no significant difference in alpha diversity (p = 0.8) or beta-diversity (p = 0.7) between the pCR and RD groups. However, relative to patients with RD, the gut microbiome in patients with pCR was enriched for the Bifidobacterium longum species (p = 0.03). The gut microbiome in patients with RD was enriched for Lachnospiraceae (p = 0.03) at the genus level and the Bacteroides thetaiotaomicron species (p = 0.02). Conclusions: We have demonstrated significant differences in the gut microbial composition in patients with pCR as compared to patients with RD. Further investigation in larger studies is needed to support therapeutic exploration of gut microbiome modulation in TNBC patients receiving chemotherapy such as probiotic supplementation or fecal microbiota transplant.

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