The role of gut microbiota in health and disease: In vitro modeling of host-microbe interactions at the aerobe-anaerobe interphase of the human gut

ABSTRACTThe mammalian gut contains a complex assembly of commensal microbes termed microbiota. Although much has been learned about the role of these microbes in health, the mechanisms underlying these functions are ill defined. We have recently shown that the mammalian gut contains thousands of small molecules, most of which are currently unidentified. Therefore, we hypothesized that these molecules function as chemical cues used by hosts and microbes during their interactions in health and disease. Thus, a search was initiated to identify molecules produced by the microbiota that are sensed by pathogens. We found that a secreted molecule produced by clostridia acts as a strong repressor ofSalmonellavirulence, obliterating expression of theSalmonellapathogenicity island 1 as well as host cell invasion. It has been known for decades that the microbiota protects its hosts from invading pathogens, and these data suggest that chemical sensing may be involved in this phenomenon. Further investigations should reveal the exact biological role of this molecule as well as its therapeutic potential.IMPORTANCEMicrobes can communicate through the production and sensing of small molecules. Within the complex ecosystem formed by commensal microbes living in and on the human body, it is likely that these molecular messages are used extensively during the interactions between different microbial species as well as with host cells. Deciphering such a molecular dialect will be fundamental to our understanding of host-microbe interactions in health and disease and may prove useful for the design of new therapeutic strategies that target these mechanisms of communication.

Download Full-text

The Use of Defined Microbial Communities To Model Host-Microbe Interactions in the Human Gut

Microbiology and Molecular Biology Reviews ◽

10.1128/mmbr.00054-18 ◽

2019 ◽

Vol 83 (2) ◽

Cited By ~ 19

Author(s):

Janneke Elzinga ◽

John van der Oost ◽

Willem M. de Vos ◽

Hauke Smidt

Keyword(s):

Gut Microbiota ◽

Microbial Communities ◽

Well Being ◽

Human Gut ◽

Human Host ◽

Advantages And Disadvantages ◽

Human Gut Microbiota ◽

Microbe Interactions ◽

Host Microbe Interactions

SUMMARYThe human intestinal ecosystem is characterized by a complex interplay between different microorganisms and the host. The high variation within the human population further complicates the quest toward an adequate understanding of this complex system that is so relevant to human health and well-being. To study host-microbe interactions, defined synthetic bacterial communities have been introduced in gnotobiotic animals or in sophisticatedin vitrocell models. This review reinforces that our limited understanding has often hampered the appropriate design of defined communities that represent the human gut microbiota. On top of this, some communities have been applied toin vivomodels that differ appreciably from the human host. In this review, the advantages and disadvantages of using defined microbial communities are outlined, and suggestions for future improvement of host-microbe interaction models are provided. With respect to the host, technological advances, such as the development of a gut-on-a-chip system and intestinal organoids, may contribute to more-accuratein vitromodels of the human host. With respect to the microbiota, due to the increasing availability of representative cultured isolates and their genomic sequences, our understanding and controllability of the human gut “core microbiota” are likely to increase. Taken together, these advancements could further unravel the molecular mechanisms underlying the human gut microbiota superorganism. Such a gain of insight would provide a solid basis for the improvement of pre-, pro-, and synbiotics as well as the development of new therapeutic microbes.

Download Full-text

Mucosal microbial parasites/symbionts in health and disease: an integrative overview

Parasitology ◽

10.1017/s0031182019000647 ◽

2019 ◽

Vol 146 (9) ◽

pp. 1109-1115 ◽

Cited By ~ 3

Author(s):

Robert P. Hirt

Keyword(s):

Host Interactions ◽

Detection Techniques ◽

Symbiotic Relationships ◽

Life Styles ◽

Mucosal Surfaces ◽

Microbe Interactions ◽

Health And Disease ◽

Host Microbe Interactions ◽

Species Being

AbstractMicrobial parasites adapted to thrive at mammalian mucosal surfaces have evolved multiple times from phylogenetically distant lineages into various extracellular and intracellular life styles. Their symbiotic relationships can range from commensalism to parasitism and more recently some host–parasites interactions are thought to have evolved into mutualistic associations too. It is increasingly appreciated that this diversity of symbiotic outcomes is the product of a complex network of parasites–microbiota–host interactions. Refinement and broader use of DNA based detection techniques are providing increasing evidence of how common some mucosal microbial parasites are and their host range, with some species being able to swap hosts, including from farm and pet animals to humans. A selection of examples will illustrate the zoonotic potential for a number of microbial parasites and how some species can be either disruptive or beneficial nodes in the complex networks of host–microbe interactions disrupting or maintaining mucosal homoeostasis. It will be argued that mucosal microbial parasitic diversity will represent an important resource to help us dissect through comparative studies the role of host–microbe interactions in both human health and disease.

Download Full-text

Gut Microbiota and Iron: The Crucial Actors in Health and Disease

Pharmaceuticals ◽

10.3390/ph11040098 ◽

2018 ◽

Vol 11 (4) ◽

pp. 98 ◽

Cited By ~ 44

Author(s):

Bahtiyar Yilmaz ◽

Hai Li

Keyword(s):

Gut Microbiota ◽

Inflammatory Diseases ◽

Life Forms ◽

Iron Availability ◽

Human Beings ◽

Human Gastrointestinal Tract ◽

Dynamic Modulation ◽

Microbe Interactions ◽

Health And Disease ◽

Host Microbe Interactions

Iron (Fe) is a highly ample metal on planet earth (~35% of the Earth’s mass) and is particularly essential for most life forms, including from bacteria to mammals. Nonetheless, iron deficiency is highly prevalent in developing countries, and oral administration of this metal is so far the most effective treatment for human beings. Notably, the excessive amount of unabsorbed iron leave unappreciated side effects at the highly interactive host–microbe interface of the human gastrointestinal tract. Recent advances in elucidating the molecular basis of interactions between iron and gut microbiota shed new light(s) on the health and pathogenesis of intestinal inflammatory diseases. We here aim to present the dynamic modulation of intestinal microbiota by iron availability, and conversely, the influence on dietary iron absorption in the gut. The central part of this review is intended to summarize our current understanding about the effects of luminal iron on host–microbe interactions in the context of human health and disease.

Download Full-text

In vitro model insights into the role of human gut microbiota on arsenic bioaccessibility and its speciation in soils

Environmental Pollution ◽

10.1016/j.envpol.2020.114580 ◽

2020 ◽

Vol 263 ◽

pp. 114580 ◽

Cited By ~ 1

Author(s):

Haifeng Chi ◽

Yanwei Hou ◽

Guofeng Li ◽

Youchi Zhang ◽

Frédéric Coulon ◽

...

Keyword(s):

Gut Microbiota ◽

In Vitro Model ◽

Human Gut ◽

Human Gut Microbiota ◽

Vitro Model

Download Full-text

The gut microbial metabolome: modulation of cancer risk in obese individuals

Proceedings of The Nutrition Society ◽

10.1017/s0029665112002881 ◽

2012 ◽

Vol 72 (1) ◽

pp. 178-188 ◽

Cited By ~ 16

Author(s):

Wendy R. Russell ◽

Sylvia H. Duncan ◽

Harry J. Flint

Keyword(s):

Gut Microbiota ◽

Genetic Factors ◽

Microbial Metabolism ◽

Health Concern ◽

Human Gut ◽

Alcoholic Fatty Liver ◽

Health And Disease ◽

Diet And Lifestyle ◽

Alcoholic Fatty Liver Disease

Obesity is a critical health concern and although genetic factors may predispose an individual to become obese, changes in diet and lifestyle over the last few decades are likely to be significant contributors. Even so, it has been suggested that the causes of the current obesity crisis are not simply explained by changes in eating and exercise habits. Evidence suggests that the gut microbiota may play an important role in obesity and may be a factor in the development of associated disease including diabetes, CVD, non-alcoholic fatty liver disease and cancer. There have been tremendous advances in knowledge regarding the composition of human gut microbiota, but less is known about their function and role within the human host. It is becoming widely accepted that the products of microbial metabolism influence human health and disease, particularly with respect to immune response and inflammation. However, in most cases, the products of microbial metabolism are uncharacterised and their mechanism of action remains unknown. This review addresses the role of the metabolites produced by gut microbiota in cancer and obesity. It is clear that only if the link between microbial diversity and metabolic functionality is firmly established, will the mechanism by which gut microbiota maintains health or contributes to disease development be elucidated.

Download Full-text

Introduction to the human gut microbiota

Biochemical Journal ◽

10.1042/bcj20160510 ◽

2017 ◽

Vol 474 (11) ◽

pp. 1823-1836 ◽

Cited By ~ 478

Author(s):

Elizabeth Thursby ◽

Nathalie Juge

Keyword(s):

Gut Microbiota ◽

Inflammatory Diseases ◽

Intestinal Bacteria ◽

Life Time ◽

Gi Tract ◽

Human Gut ◽

Human Gut Microbiota ◽

Microbe Interactions ◽

Host Microbe Interactions ◽

Dynamic Population

The human gastrointestinal (GI) tract harbours a complex and dynamic population of microorganisms, the gut microbiota, which exert a marked influence on the host during homeostasis and disease. Multiple factors contribute to the establishment of the human gut microbiota during infancy. Diet is considered as one of the main drivers in shaping the gut microbiota across the life time. Intestinal bacteria play a crucial role in maintaining immune and metabolic homeostasis and protecting against pathogens. Altered gut bacterial composition (dysbiosis) has been associated with the pathogenesis of many inflammatory diseases and infections. The interpretation of these studies relies on a better understanding of inter-individual variations, heterogeneity of bacterial communities along and across the GI tract, functional redundancy and the need to distinguish cause from effect in states of dysbiosis. This review summarises our current understanding of the development and composition of the human GI microbiota, and its impact on gut integrity and host health, underlying the need for mechanistic studies focusing on host–microbe interactions.

Download Full-text

The Controversial Role of Human Gut Lachnospiraceae

Microorganisms ◽

10.3390/microorganisms8040573 ◽

2020 ◽

Vol 8 (4) ◽

pp. 573 ◽

Cited By ~ 18

Author(s):

Mirco Vacca ◽

Giuseppe Celano ◽

Francesco Maria Calabrese ◽

Piero Portincasa ◽

Marco Gobbetti ◽

...

Keyword(s):

Fatty Acids ◽

Gut Microbiota ◽

Short Chain Fatty Acids ◽

Intestinal Lumen ◽

Human Gut ◽

The Core ◽

Host Diet ◽

Health And Disease ◽

Host Physiology

The complex polymicrobial composition of human gut microbiota plays a key role in health and disease. Lachnospiraceae belong to the core of gut microbiota, colonizing the intestinal lumen from birth and increasing, in terms of species richness and their relative abundances during the host’s life. Although, members of Lachnospiraceae are among the main producers of short-chain fatty acids, different taxa of Lachnospiraceae are also associated with different intra- and extraintestinal diseases. Their impact on the host physiology is often inconsistent across different studies. Here, we discuss changes in Lachnospiraceae abundances according to health and disease. With the aim of harnessing Lachnospiraceae to promote human health, we also analyze how nutrients from the host diet can influence their growth and how their metabolites can, in turn, influence host physiology.

Download Full-text

Metabolic functions of the human gut microbiota: the role of metalloenzymes

Natural Product Reports ◽

10.1039/c8np00074c ◽

2019 ◽

Vol 36 (4) ◽

pp. 593-625 ◽

Cited By ~ 15

Author(s):

Lauren J. Rajakovich ◽

Emily P. Balskus

Keyword(s):

Gut Microbiota ◽

Human Gut ◽

Human Gut Microbiota ◽

Metabolic Functions ◽

Host Health ◽

Health And Disease

Metalloenzymes play central roles in metabolic functions of the human gut microbiota that are associated with host health and disease.

Download Full-text

Gut health: predictive biomarkers for preventive medicine and development of functional foods

British Journal Of Nutrition ◽

10.1017/s0007114509993400 ◽

2010 ◽

Vol 103 (10) ◽

pp. 1539-1544 ◽

Cited By ~ 17

Author(s):

Raish Oozeer ◽

Maria Rescigno ◽

R. Paul Ross ◽

Jan Knol ◽

Michael Blaut ◽

...

Keyword(s):

Gut Microbiota ◽

Predictive Biomarkers ◽

Gut Health ◽

Human Gut ◽

Observation Study ◽

Industry Collaboration ◽

Health And Disease ◽

Micro Organisms ◽

First Time

There is an urgent need to develop and validate a series of biomarkers, which accurately measure and inform on how the human gut microbiota can affect human health. The human gut hosts a complex community of micro-organisms, with unique features in each individual. The functional role of this gut microbiota in health and disease is increasingly evident, but poorly understood. Comprehension of this ecosystem implies a significant challenge in the elucidation of interactions between all of its components, but promises a paradigm shift in preventive nutrition and medicine. ‘Omics’ technologies for the first time offer tools of sufficient subtlety to tackle this challenge. However, these techniques must be allied with traditional skills of the microbial physiologist, which are in danger of being lost. Targeting these efforts at the identification of biomarkers associated with gut health will require access to a ‘biobank’ from a pan-European or worldwide observation study, which would include samples taken with appropriate frequency from healthy individuals of different ages. This offers a pragmatic opportunity for a unique food and pharmaceutical industry collaboration.

Download Full-text