Impact of Microbiota Transplant on Resistome of Gut Microbiota in Gnotobiotic Piglets and Human Subjects

The human intestinal microbial ecosystem plays an important role in maintaining health. A multitude of diseases including diarrhoea, gastrointestinal inflammatory disorders, such as necrotising enterocolitis (NEC) of neonates, and obesity are linked to microbial composition and metabolic activity. Therefore, research on possible dietary strategies influencing microbial composition and activity, both preventive and curative, is being accomplished. Interest has focused on pre- and probiotics that stimulate the intestinal production of beneficial bacterial metabolites such as butyrate, and beneficially affect microbial composition. The suitability of an animal model to study dietary linked diseases is of much concern. The physiological similarity between humans and pigs in terms of digestive and associated metabolic processes places the pig in a superior position over other non-primate models. Furthermore, the pig is a human-sized omnivorous animal with comparable nutritional requirements, and shows similarities to the human intestinal microbial ecosystem. Also, the pig has been used as a model to assess microbiota–health interactions, since pigs exhibit similar syndromes to humans, such as NEC and partly weanling diarrhoea. In contrast, when using rodent models to study diet–microbiota–health interactions, differences between rodents and humans have to be considered. For example, studies with mice and human subjects assessing possible relationships between the composition and metabolic activity of the gut microbiota and the development of obesity have shown inconsistencies in results between studies. The present review displays the similarities and differences in intestinal microbial ecology between humans and pigs, scrutinising the pig as a potential animal model, with regard to possible health effects.

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Fatty Acid Diets: Regulation of Gut Microbiota Composition and Obesity and Its Related Metabolic Dysbiosis

International Journal of Molecular Sciences ◽

10.3390/ijms21114093 ◽

2020 ◽

Vol 21 (11) ◽

pp. 4093 ◽

Cited By ~ 1

Author(s):

David Johane Machate ◽

Priscila Silva Figueiredo ◽

Gabriela Marcelino ◽

Rita de Cássia Avellaneda Guimarães ◽

Priscila Aiko Hiane ◽

...

Keyword(s):

Fatty Acids ◽

Health Promotion ◽

Fatty Acid ◽

Gut Microbiota ◽

Human Subjects ◽

Monounsaturated Fatty Acids ◽

Microbiota Composition ◽

High Fat ◽

Gut Microbiota Composition ◽

Chain Fatty Acids

Long-term high-fat dietary intake plays a crucial role in the composition of gut microbiota in animal models and human subjects, which affect directly short-chain fatty acid (SCFA) production and host health. This review aims to highlight the interplay of fatty acid (FA) intake and gut microbiota composition and its interaction with hosts in health promotion and obesity prevention and its related metabolic dysbiosis. The abundance of the Bacteroidetes/Firmicutes ratio, as Actinobacteria and Proteobacteria species are associated with increased SCFA production, reported high-fat diet rich in medium-chain fatty acids (MCFAs), monounsaturated fatty acids (MUFAs), and n–3 polyunsaturated fatty acids (PUFAs) as well as low-fat diets rich in long-chain fatty acids (LCFAs). SCFAs play a key role in health promotion and prevention and, reduction and reversion of metabolic syndromes in the host. Furthermore, in this review, we discussed the type of fatty acids and their amount, including the administration time and their interplay with gut microbiota and its results about health or several metabolic dysbioses undergone by hosts.

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A sparse covarying unit that describes healthy and impaired human gut microbiota development

Science ◽

10.1126/science.aau4735 ◽

2019 ◽

Vol 365 (6449) ◽

pp. eaau4735 ◽

Cited By ~ 31

Author(s):

Arjun S. Raman ◽

Jeanette L. Gehrig ◽

Siddarth Venkatesh ◽

Hao-Wei Chang ◽

Matthew C. Hibberd ◽

...

Keyword(s):

Gut Microbiota ◽

Financial Markets ◽

Low Income ◽

Low Income Countries ◽

Healthy Children ◽

Human Gut ◽

Human Gut Microbiota ◽

Formidable Challenge ◽

Gnotobiotic Piglets ◽

Milk Feeding

Characterizing the organization of the human gut microbiota is a formidable challenge given the number of possible interactions between its components. Using a statistical approach initially applied to financial markets, we measured temporally conserved covariance among bacterial taxa in the microbiota of healthy members of a Bangladeshi birth cohort sampled from 1 to 60 months of age. The results revealed an “ecogroup” of 15 covarying bacterial taxa that provide a concise description of microbiota development in healthy children from this and other low-income countries, and a means for monitoring community repair in undernourished children treated with therapeutic foods. Features of ecogroup population dynamics were recapitulated in gnotobiotic piglets as they transitioned from exclusive milk feeding to a fully weaned state consuming a representative Bangladeshi diet.

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Why interindividual variation in response to consumption of plant food bioactives matters for future personalised nutrition

Proceedings of The Nutrition Society ◽

10.1017/s0029665120000014 ◽

2020 ◽

Vol 79 (2) ◽

pp. 225-235 ◽

Cited By ~ 3

Author(s):

Christine Morand ◽

Baukje De Roos ◽

Maria Teresa Garcia-Conesa ◽

Eileen R. Gibney ◽

Rikard Landberg ◽

...

Keyword(s):

Health Status ◽

Gut Microbiota ◽

Intervention Studies ◽

Current Knowledge ◽

Human Subjects ◽

Interindividual Variation ◽

Cardiometabolic Health ◽

Plant Food ◽

Systematic Analysis ◽

Beneficial Effects

Food phytochemicals are increasingly considered to play a key role in the cardiometabolic health effects of plant foods. However, the heterogeneity in responsiveness to their intake frequently observed in clinical trials can hinder the beneficial effects of these compounds in specific subpopulations. A range of factors, including genetic background, gut microbiota, age, sex and health status, could be involved in these interindividual variations; however, the current knowledge is limited and fragmented. The European network, European Cooperation in Science and Technology (COST)-POSITIVe, has analysed, in a systematic way, existing knowledge with the aim to better understand the factors responsible for the interindividual variation in response to the consumption of the major families of plant food bioactives, regarding their bioavailability and bioefficacy. If differences in bioavailability, likely reflecting differences in human subjects’ genetics or in gut microbiota composition and functionality, are believed to underpin much of the interindividual variability, the key molecular determinants or microbial species remain to be identified. The systematic analysis of published studies conducted to assess the interindividual variation in biomarkers of cardiometabolic risk suggested some factors (such as adiposity and health status) as involved in between-subject variation. However, the contribution of these factors is not demonstrated consistently across the different compounds and biological outcomes and would deserve further investigations. The findings of the network clearly highlight that the human subjects’ intervention studies published so far are not adequate to investigate the relevant determinants of the absorption/metabolism and biological responsiveness. They also emphasise the need for a new generation of intervention studies designed to capture this interindividual variation.

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Type-2 Diabetics Reduces Spatial Variation of Microbiome Based on Extracellular Vesicles from Gut Microbes across Human Body

Scientific Reports ◽

10.1038/s41598-019-56662-x ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Geumkyung Nah ◽

Sang-Cheol Park ◽

Kangjin Kim ◽

Sungmin Kim ◽

Jaehyun Park ◽

...

Keyword(s):

Gut Microbiota ◽

Intestinal Permeability ◽

Extracellular Vesicles ◽

Human Body ◽

Healthy Subjects ◽

Human Subjects ◽

Gut Microbes ◽

Serum And Urine

AbstractAs a result of advances in sequencing technology, the role of gut microbiota in the mechanism of type-2 diabetes mellitus (T2DM) has been revealed. Studies showing wide distribution of microbiome throughout the human body, even in the blood, have motivated the investigation of the dynamics in gut microbiota across the humans. Particularly, extracellular vesicles (EVs), lipid bilayer structures secreted from the gut microbiota, have recently come into the spotlight because gut microbe-derived EVs affect glucose metabolism by inducing insulin resistance. Recently, intestine hyper-permeability linked to T2DM has also been associated with the interaction between gut microbes and leaky gut epithelium, which increases the uptake of macromolecules like lipopolysaccharide from the membranes of microbes leading to chronic inflammation. In this article, we firstly investigate the co-occurrence of stool microbes and microbe-derived EVs across serum and urine in human subjects (N = 284), showing the dynamics and stability of gut derived EVs. Stool EVs are intermediate, while the bacterial composition in both urine and serum EVs is distinct from the stool microbiome. The co-occurrence of microbes was compared between patients with T2DM (N = 29) and matched in healthy subjects (N = 145). Our results showed significantly higher correlations in patients with T2DM compared to healthy subjects across stool, serum, and urine, which could be interpreted as the dysfunction of intestinal permeability in T2DM. Therefore, the significant correlation of EVs might give insight into the pathophysiological mechanisms of T2DM, as well as the role of EVs as a biomarker in the intestinal permeability of T2DM.

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Gut microbiota in obesity and metabolic disorders

Proceedings of The Nutrition Society ◽

10.1017/s0029665110001813 ◽

2010 ◽

Vol 69 (3) ◽

pp. 434-441 ◽

Cited By ~ 147

Author(s):

Yolanda Sanz ◽

Arlette Santacruz ◽

Paola Gauffin

Keyword(s):

Body Weight ◽

Weight Gain ◽

Gut Microbiota ◽

Metabolic Disorders ◽

Dietary Intervention ◽

Body Weight Gain ◽

Human Subjects ◽

Inflammatory Factors ◽

Public Health Issue ◽

Immune Functions

Obesity is a major public health issue as it is causally related to several chronic disorders, including type-2 diabetes, CVD and cancer. Novel research shows that the gut microbiota is involved in obesity and metabolic disorders, revealing that obese animal and human subjects have alterations in the composition of the gut microbiota compared to their lean counterparts. Moreover, transplantation of the microbiota of either obese or lean mice influences body weight in the germ-free recipient mice, suggesting that the gut ecosystem is a relevant target for weight management. Indigenous gut microbes may regulate body weight by influencing the host's metabolic, neuroendocrine and immune functions. The intestinal microbiota, as a whole, provides additional metabolic functions and regulates the host's gene expression, improving the ability to extract and store energy from the diet and contributing to body-weight gain. Imbalances in the gut microbiota and increases in plasma lipopolysaccharide may also act as inflammatory factors related to the development of atherosclerosis, insulin resistance and body-weight gain. In contrast, specific probiotics, prebiotics and related metabolites might exert beneficial effects on lipid and glucose metabolism, the production of satiety peptides and the inflammatory tone related to obesity and associated metabolic disorders. This knowledge is contributing to our understanding of how environmental factors influence obesity and associated diseases, providing new opportunities to design improved dietary intervention strategies to manage these disorders.

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Effects of a gluten-free diet on gut microbiota and immune function in healthy adult human subjects

British Journal Of Nutrition ◽

10.1017/s0007114509371767 ◽

2009 ◽

Vol 102 (8) ◽

pp. 1154-1160 ◽

Cited By ~ 167

Author(s):

Giada De Palma ◽

Inmaculada Nadal ◽

Maria Carmen Collado ◽

Yolanda Sanz

Keyword(s):

Gut Microbiota ◽

Immune Function ◽

Mononuclear Cells ◽

Human Subjects ◽

Bifidobacterium Longum ◽

Gluten Free Diet ◽

Gluten Free ◽

Gut Health ◽

Peripheral Blood Mononuclear ◽

Faecal Samples

Diet influences the composition of the gut microbiota and host's health, particularly in patients suffering from food-related diseases. Coeliac disease (CD) is a permanent intolerance to cereal gluten proteins and the only therapy for the patients is to adhere to a life-long gluten-free diet (GFD). In the present preliminary study, the effects of a GFD on the composition and immune function of the gut microbiota were analysed in ten healthy subjects (mean age 30·3 years) over 1 month. Faecal microbiota was analysed by fluorescencein situhybridisation (FISH) and quantitative PCR (qPCR). The ability of faecal bacteria to stimulate cytokine production by peripheral blood mononuclear cells (PBMC) was determined by ELISA. No significant differences in dietary intake were found before and after the GFD except for reductions (P = 0·001) in polysaccharides.Bifidobacterium,Clostridium lituseburenseandFaecalibacterium prausnitziiproportions decreased (P = 0·007,P = 0·031 andP = 0·009, respectively) as a result of the GFD analysed by FISH.Bifidobacterium,LactobacillusandBifidobacterium longumcounts decreased (P = 0·020,P = 0·001 andP = 0·017, respectively), whileEnterobacteriaceaeandEscherichia colicounts increased (P = 0·005 andP = 0·003) after the GFD assessed by qPCR. TNF-α, interferon-γ, IL-10 and IL-8 production by PBMC stimulated with faecal samples was also reduced (P = 0·021,P = 0·037,P = 0·002 andP = 0·007, respectively) after the diet. Therefore, the GFD led to reductions in beneficial gut bacteria populations and the ability of faecal samples to stimulate the host's immunity. Thus, the GFD may constitute an environmental variable to be considered in treated CD patients for its possible effects on gut health.

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Linking the gut microbiota to human health

British Journal Of Nutrition ◽

10.1017/s0007114512005235 ◽

2013 ◽

Vol 109 (S2) ◽

pp. S21-S26 ◽

Cited By ~ 162

Author(s):

Virginia Robles Alonso ◽

Francisco Guarner

Keyword(s):

Gut Microbiota ◽

Microbial Communities ◽

Human Subjects ◽

Experimental Studies ◽

Adult Life ◽

Normal Growth ◽

Bioinformatic Analysis ◽

Human Gut ◽

Sequencing Technologies ◽

The Metabolic Syndrome

The human gut is the natural environment for a diverse and dynamic microbial ecosystem, whose structure and functions are presently a major target of research in biomedicine. Experimental studies in germ-free animals performed some decades ago revealed the importance of these microbial communities for normal growth and development and for the maintenance of health in adult life. The host provides habitat and nutrition to the microbial communities and derives many benefits from its symbionts that contribute to metabolic, defensive and trophic functions. Development of novel gene sequencing technologies as well as availability of powerful bioinformatic analysis tools provide new insights into the composition and structure of the human gut microbiota. There is no clear definition of the characteristics of a normal ‘healthy’ gut microbiota in human subjects, but several disease states have been associated with changes in the composition of faecal and intestinal mucosal communities, including inflammatory bowel diseases, obesity and the metabolic syndrome. Probiotics and prebiotics are used to improve symbiosis between enteric microbiota and the host or restore states of dysbiosis.

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A Computational Framework to Quantify Host-Microbiome Interactions in Clostridioides Difficile Infection

10.21203/rs.3.rs-65421/v1 ◽

2020 ◽

Author(s):

Shanlin Ke ◽

Nira R. Pollock ◽

Xu-wen Wang ◽

Xinhua Chen ◽

Kaitlyn Daugherty ◽

...

Keyword(s):

Random Forest ◽

Gut Microbiota ◽

Gut Microbiome ◽

Human Subjects ◽

Disease Diagnosis ◽

Healthcare Associated Infection ◽

Immune Markers ◽

Computational Framework ◽

Treatment And Prevention ◽

Clostridioides Difficile

Abstract Background: Clostridioides difficile infection (CDI) is the most common cause of healthcare–associated infection and an important cause of morbidity and mortality among hospitalized patients. A comprehensive understanding of C. difficile infection (CDI) pathogenesis is crucial for disease diagnosis, treatment and prevention. To achieve that, a quantitative study of host-microbiome interactions in CDI is a prerequisite. Yet, an effective computational framework to quantify host-microbiome interactions in CDI was lacking. Methods: Here, we characterized gut microbial compositions and abroad panel of immunological markers in a comprehensive clinical cohort of 243 well-characterized human subjects with four different C. difficile infection/colonization statuses (CDI, Asymptomatic Carriage, Non-CDI Diarrhea, and Control). Based on microbial and immunological features, we developed a computational framework to detect CDI status using random forest and symbolic classification models.Results: First, by calculating the correlations between microbial compositions and the circulating levels of host immune markers for each of the four phenotype groups, we found that the interactions between gut microbiota and host immune markers are very sensitive to the status of C. difficile colonization and infection. Second, we demonstrated that incorporating both gut microbiome and host immune marker data into random forest classifiers can better distinguish CDI from other groups than can either type of data alone. Finally, we performed symbolic classification using selected features from random forest classifiers to derive simple mathematic formulas that explicitly model the interactions between gut microbiome and host immune markers.Conclusions: Overall, this study provides an effective computational framework to quantify the role of the intricate interactions between gut microbiota and host immune markers in CDI pathogenesis. This framework may inform the design of future diagnostic and therapeutic strategies.

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