Use of pigs as a potential model for research into dietary modulation of the human gut microbiota

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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The use of non-rodent model species in microbiota studies

Laboratory Animals ◽

10.1177/0023677219834593 ◽

2019 ◽

Vol 53 (3) ◽

pp. 259-270 ◽

Cited By ~ 4

Author(s):

Aaron C. Ericsson

Keyword(s):

Gut Microbiota ◽

Potential Model ◽

Rodent Model ◽

Rodent Models ◽

Prospective Evaluation ◽

Model Species ◽

Human Gut ◽

Causative Factors ◽

Disease Initiation ◽

Made In

In recent years, tremendous advances have been made in our ability to characterize complex microbial communities such as the gut microbiota, and numerous surveys of the human gut microbiota have identified countless associations between different compositional attributes of the gut microbiota and adverse health conditions. However, most of these findings in humans are purely correlative and animal models are required for prospective evaluation of such changes as causative factors in disease initiation or progression. As in most fields of biomedical research, microbiota-focused studies are predominantly performed in mouse or rat models. Depending on the field of research and experimental question or objective, non-rodent models may be preferable due to better translatability or an inability to use rodents for various reasons. The following review describes the utility and limitations of several non-rodent model species for research on the microbiota and its influence on host physiology and disease. In an effort to balance the breadth of potential model species with the amount of detail provided, four model species are discussed: zebrafish, dogs, pigs, and rabbits.

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Distinct composition and metabolic functions of human gut microbiota are associated with cachexia in lung cancer patients

The ISME Journal ◽

10.1038/s41396-021-00998-8 ◽

2021 ◽

Author(s):

Yueqiong Ni ◽

Zoltan Lohinai ◽

Yoshitaro Heshiki ◽

Balazs Dome ◽

Judit Moldvay ◽

...

Keyword(s):

Lung Cancer ◽

Gut Microbiota ◽

Cancer Patients ◽

Gut Microbiome ◽

Human Gut ◽

Microbial Composition ◽

Shotgun Metagenomics ◽

Lung Cancer Patients ◽

Microbial Species ◽

Functional Pathways

AbstractCachexia is associated with decreased survival in cancer patients and has a prevalence of up to 80%. The etiology of cachexia is poorly understood, and limited treatment options exist. Here, we investigated the role of the human gut microbiome in cachexia by integrating shotgun metagenomics and plasma metabolomics of 31 lung cancer patients. The cachexia group showed significant differences in the gut microbial composition, functional pathways of the metagenome, and the related plasma metabolites compared to non-cachectic patients. Branched-chain amino acids (BCAAs), methylhistamine, and vitamins were significantly depleted in the plasma of cachexia patients, which was also reflected in the depletion of relevant gut microbiota functional pathways. The enrichment of BCAAs and 3-oxocholic acid in non-cachectic patients were positively correlated with gut microbial species Prevotella copri and Lactobacillus gasseri, respectively. Furthermore, the gut microbiota capacity for lipopolysaccharides biosynthesis was significantly enriched in cachectic patients. The involvement of the gut microbiome in cachexia was further observed in a high-performance machine learning model using solely gut microbial features. Our study demonstrates the links between cachectic host metabolism and specific gut microbial species and functions in a clinical setting, suggesting that the gut microbiota could have an influence on cachexia with possible therapeutic applications.

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New View on Dietary Fiber Selection for Predictable Shifts in Gut Microbiota

mBio ◽

10.1128/mbio.02179-19 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 3

Author(s):

T. M. Cantu-Jungles ◽

B. R. Hamaker

Keyword(s):

Gut Microbiota ◽

Microbial Communities ◽

Dietary Fiber ◽

Physical Characteristics ◽

Dietary Fibers ◽

Human Gut ◽

Microbial Composition ◽

Human Gut Microbiota ◽

Selection For ◽

Fiber Selection

ABSTRACT Dietary fibers can be utilized to shape the human gut microbiota. However, the outcomes from most dietary fibers currently used as prebiotics are a result of competition between microbes with overlapping abilities to utilize these fibers. Thus, divergent fiber responses are observed across individuals harboring distinct microbial communities. Here, we propose that dietary fibers can be classified hierarchically according to their specificity toward gut microbes. Highly specific fibers harbor chemical and physical characteristics that allow them to be utilized by only a narrow group of bacteria within the gut, reducing competition for that substrate. The use of such fibers as prebiotics targeted to specific microbes would result in predictable shifts independent of the background microbial composition.

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Diet drives quick changes in the metabolic activity and composition of human gut microbiota in a validated in vitro gut model

Research in Microbiology ◽

10.1016/j.resmic.2015.09.006 ◽

2016 ◽

Vol 167 (2) ◽

pp. 114-125 ◽

Cited By ~ 41

Author(s):

Marisol Aguirre ◽

Anat Eck ◽

Marjorie E. Koenen ◽

Paul H.M. Savelkoul ◽

Andries E. Budding ◽

...

Keyword(s):

Gut Microbiota ◽

Metabolic Activity ◽

Human Gut ◽

Human Gut Microbiota

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Understanding Microbiome Data: A Primer for Clinicians

Digestive Diseases ◽

10.1159/000437034 ◽

2015 ◽

Vol 33 (Suppl. 1) ◽

pp. 11-16 ◽

Cited By ~ 13

Author(s):

Philippe Seksik ◽

Cécilia Landman

Keyword(s):

Gut Microbiota ◽

Bacterial Colonization ◽

Data Sets ◽

Human Gut ◽

Microbial Composition ◽

Host Determinants ◽

Host Interaction ◽

Bacterial Genes ◽

Micro Organisms ◽

Microbiome Data

The human gut contains 1014 bacteria and many other micro-organisms such as Archaea, viruses and fungi. This gut microbiota has co-evolved with host determinants through symbiotic and co-dependent relationships. Bacteria, which represent 10 times the number of human cells, form the most depicted part of this black box owing to new tools. Re-evaluating the gut microbiota showed how this entity participates in gut physiology and beyond this in human health. Studying and handling this real ‘hidden organ' remains a challenge for clinicians. In this review, we aimed to bring information about gut microbiota, its structure, its roles and the way to capture and measure it. After bacterial colonization in infant, intestinal microbial composition is unique for each individual although more than 95% can be assigned to 4 major phyla. Besides its biodiversity, the major characteristics of gut microbiota are stability over time and resilience after perturbation. In pathological situations, dysbiosis (i.e. imbalance in gut microbiota composition) is observed with a loss in overall diversity. Dysbiosis associated with inflammatory bowel disease was specified with the reduction in biodiversity, the decreased representation of different taxa in the Firmicutes phylum and an increase in Gammaproteobacteria. Beyond depicting gut microbial composition, metagenomics allows the description of the combined genomes of the microorganisms present in the gut, giving access to their potential functions. In fact, each individual overall microbial metagenome outnumbers the size of human genome by a factor of 150. Besides a functional core in which there is redundancy for mandatory functions assuring the robustness of the ecosystem, human gut contains an important diversity and high number of non-redundant bacterial genes. Clinical data, treatment and all the factors able to influence microbiome should enter integrated big data sets to put in light pathways of interplay within the supra organism composed of gut microbiome and host. A better understanding of dynamics within human gut microbiota and microbes-host interaction will allow new insight into gut pathophysiology especially regarding resilience mechanisms and dysbiosis onset and maintenance. This will lead to description of biomarkers of diseases, development of new probiotics/prebiotics and new therapies.

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Effect of Diet on the Gut Microbiota: Rethinking Intervention Duration

Nutrients ◽

10.3390/nu11122862 ◽

2019 ◽

Vol 11 (12) ◽

pp. 2862 ◽

Cited By ~ 24

Author(s):

Emily R Leeming ◽

Abigail J Johnson ◽

Tim D Spector ◽

Caroline I Le Roy

Keyword(s):

Gut Microbiota ◽

Current Knowledge ◽

Dietary Interventions ◽

Human Gut ◽

Short Term ◽

Modifiable Factor ◽

Health And Disease ◽

Major Factors ◽

Dietary Strategies

The human gut is inhabited by trillions of microorganisms composing a dynamic ecosystem implicated in health and disease. The composition of the gut microbiota is unique to each individual and tends to remain relatively stable throughout life, yet daily transient fluctuations are observed. Diet is a key modifiable factor influencing the composition of the gut microbiota, indicating the potential for therapeutic dietary strategies to manipulate microbial diversity, composition, and stability. While diet can induce a shift in the gut microbiota, these changes appear to be temporary. Whether prolonged dietary changes can induce permanent alterations in the gut microbiota is unknown, mainly due to a lack of long-term human dietary interventions, or long-term follow-ups of short-term dietary interventions. It is possible that habitual diets have a greater influence on the gut microbiota than acute dietary strategies. This review presents the current knowledge around the response of the gut microbiota to short-term and long-term dietary interventions and identifies major factors that contribute to microbiota response to diet. Overall, further research on long-term diets that include health and microbiome measures is required before clinical recommendations can be made for dietary modulation of the gut microbiota for health.

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Exercise and human gut microbiota: a systemic review

Proceedings of The Nutrition Society ◽

10.1017/s002966512000590x ◽

2020 ◽

Vol 79 (OCE2) ◽

Author(s):

Huiwen Xu ◽

Lourdes Ortiz Álvarez ◽

Borja Martínez-Téllez ◽

Jonatan Ruiz Ruiz

Keyword(s):

Physical Activity ◽

Gut Microbiota ◽

Alpha Diversity ◽

Healthy Adults ◽

Human Gut ◽

Cross Sectional ◽

Microbial Ecosystem ◽

Exercise Interventions ◽

Human Gut Microbiota ◽

Cross Sectional Studies

AbstractBackground:Eubiosis is the intestinal microbial ecosystem balance between human and microorganisms, whereas a disbalance in this intestinal microbial ecosystem is known as dysbiosis. The relationship between exercise with gut microbiota in humans is poorly studied, although it seems that one of the possible ways to restore eubiosis could be via exercise. This systematic review aimed to examine the scientific literature available on the influence of exercise in the gut microbiota of healthy adults.Methods:A systematic and comprehensive literature search was conducted in PubMed and Web of Science (WOS) from their inception to April 2019. Search terms used were: “Gastrointestinal Microbiome”, “Fecal Microbiota”, “Cecal Microbiota”, “Faecal Microbiota, “Exercises”, “Training” and “Human”.Results:The initial search retrieved 218 articles and 15 met the inclusion criteria of which 9 were cross-sectional, 3 acute and 3 chronic exercise interventions. Higher levels of physical activity or VO2max were positively associated with alpha-diversity in the 85.7% of the cross-sectional studies (n = 6). We found controversial findings between levels of physical activity or VO2max with Firmicutes, Bacteroidetes and Proteobacteria phylum over cross-sectional studies. However, some studies found that higher levels of physical activity or VO2max were positively related with Verrumicrobia and Actinobacteria, as well as their levels increased after the exercise interventions studies. Furthermore, higher levels of physical activity or VO2max were positively related with short-chain-fatty-acids (SCFAs), as well as their levels increased after a chronic intervention.Discussion:The muscle-gut axis is based on the contraction of skeletal muscle during exercise due to the release of myokines. This myokines that seem to play a role in mediating the glucagon-like peptide-1 (GLP-1) secretion in the gut during exercise. GLP-1 is one of the key incretins involved in the whole-body metabolism. On other hand, the gut-muscle axis, relies that the gut microbiota is able to produce SCFAs, which are mediator of mitochondrial energy metabolism in skeletal muscles.Conclusion:Higher levels of physical activity or VO2max are positively related with higher levels of alpha diversity and some phylum in healthy adults. Moreover, both acute and chronic exercises only influence some phylum. However, the high heterogeneity between studies hampers to draw stronger conclusions. Therefore, further studies are needed to understand the possible mechanism about how exercise could affect healthy human gut microbiota.

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Production of conjugated linoleic acid (CLA): effect of inulin on microbial composition and CLA concentration in a human intestinal model

Proceedings of The Nutrition Society ◽

10.1017/s0029665120005777 ◽

2020 ◽

Vol 79 (OCE2) ◽

Author(s):

Ilaria Carafa ◽

Domenico Masuero ◽

Urska Vrhovsek ◽

Giovanni Bittante ◽

Elena Franciosi ◽

...

Keyword(s):

Linoleic Acid ◽

Gut Microbiota ◽

Relative Abundance ◽

Illumina Miseq ◽

Ultra Performance Liquid Chromatography ◽

Rrna Gene ◽

Human Gut ◽

Microbial Composition ◽

Human Gut Microbiota

AbstractConjugated linoleic acids (CLAs) show a number of putative health-promoting activities including anti-carcinogenic, anti-adipogenic, anti-diabetogenic, anti-inflammatory and antioxidant actions. CLAs are naturally produced by ruminal bacteria and several studies demonstrate that various lactobacilli and bifidobacteria are also able to produce CLAs in vitro from linoleic acid (LA). However, the ability of the human gut microbiota to produce CLA is less extensively studied. Our hypothesis is that the human gut microbiota is able to convert LA to CLA, and that the readily fermentable fiber inulin would positively modulate the growth of CLA-producing bacteria and, consequently increase the CLA content in the intestine.The capability of the faecal microbiota from five healthy donors to produce CLA was tested in anaerobic batch cultures for 48 hours at pH 5.5 and 6.5. Test treatments were linoleic acid (LA; 1 mg/mL) + bovine serum albumin (BSA; 0.2 mg/mL), and LA (1 mg/mL) + BSA (0.2 mg/mL) + inulin (1%, w/v) compared to a control BSA (0.2 mg/mL) fermentation. The microbial composition was analyzed 0, 24 and 48 hours after starting the fermentation by 16S rRNA gene Illumina MiSeq sequencing (V3-V4 region). CLAs were quantified by Ultra performance liquid chromatography - tandem mass spectrometer (UPLC-MS/MS) and bi-dimensional gas chromatography (GC x GC).The inclusion of LA + BSA + inulin at pH 5.5 significantly increased the relative abundance of Collinsella aerofaciens (p < 0.05), and tended to increase the relative abundance of bifidobacteria. LA + BSA + inulin at both pH 5.5 and 6.5 reduced the relative abundance of Parabacteroides, Bilophila, Clostridia and Enterobacteriaceae (p < 0.05). The concentration of CLA, in particular the isomer cis9,trans11 C18:2, was significantly higher in the LA + BSA + inulin group at pH 5.5 after 24 and 48 hours fermentation.The data show that the treatment LA + BSA + inulin at pH 5.5 induce substantial changes in microbiota composition, including bifidogenesis and CLA production in a human intestinal microbiota model. The changes of relative abundance detected are consistent with changes in gut bacteria previously linked to human health. Collinsella aerofaciens has been reported for reducing bloating, in particular in subjects suffering from irritable bowel syndrome, while Clostridia, Bilophila and Enterobacteriaceae causes human infections. In addition, the increase of bifidobacteria and LAB, which have previously been shown in vitro to produce CLA, may also be involved in CLA production under simulated cecal microbiome. These preclinical observations warrant confirmation in suitably designed animal and human mechanistic studies.

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Novel approaches for analysing gut microbes and dietary polyphenols: challenges and opportunities

Microbiology ◽

10.1099/mic.0.042127-0 ◽

2010 ◽

Vol 156 (11) ◽

pp. 3224-3231 ◽

Cited By ~ 122

Author(s):

R. A. Kemperman ◽

S. Bolca ◽

L. C. Roger ◽

E. E. Vaughan

Keyword(s):

Gut Microbiota ◽

Health Effects ◽

Fruit And Vegetables ◽

Human Gut ◽

Microbial Composition ◽

Dietary Polyphenols ◽

Host Health ◽

The Impact

Polyphenols, ubiquitously present in the food we consume, may modify the gut microbial composition and/or activity, and moreover, may be converted by the colonic microbiota to bioactive compounds that influence host health. The polyphenol content of fruit and vegetables and derived products is implicated in some of the health benefits bestowed on eating fruit and vegetables. Elucidating the mechanisms behind polyphenol metabolism is an important step in understanding their health effects. Yet, this is no trivial assignment due to the diversity encountered in both polyphenols and the gut microbial composition, which is further confounded by the interactions with the host. Only a limited number of studies have investigated the impact of dietary polyphenols on the complex human gut microbiota and these were mainly focused on single polyphenol molecules and selected bacterial populations. Our knowledge of gut microbial genes and pathways for polyphenol bioconversion and interactions is poor. Application of specific in vitro or in vivo models mimicking the human gut environment is required to analyse these diverse interactions. A particular benefit can now be gained from next-generation analytical tools such as metagenomics and metatranscriptomics allowing a wider, more holistic approach to the analysis of polyphenol metabolism. Understanding the polyphenol–gut microbiota interactions and gut microbial bioconversion capacity will facilitate studies on bioavailability of polyphenols in the host, provide more insight into the health effects of polyphenols and potentially open avenues for modulation of polyphenol bioactivity for host 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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