Elsevier

Diabetes & Metabolism

Volume 35, Issue 4, September 2009, Pages 262-272
Diabetes & Metabolism

Review
Intestinal microflora and metabolic diseasesFlore intestinale et maladies métaboliques

https://doi.org/10.1016/j.diabet.2009.03.003Get rights and content

Abstract

Recent advances in molecular sequencing technology have allowed researchers to answer major questions regarding the relationship between a vast genomic diversity—such as found in the intestinal microflora—and host physiology. Over the past few years, it has been established that, in obesity, type 1 diabetes and Crohn's disease—to cite but a few—the intestinal microflora play a pathophysiological role and can induce, transfer or prevent the outcome of such conditions. A few of the molecular vectors responsible for this regulatory role have been determined. Some are related to control of the immune, vascular, endocrine and nervous systems located in the intestines. However, more important is the fact that the intestinal microflora-to-host relationship is bidirectional, with evidence of an impact of the host genome on the intestinal microbiome. This means that the ecology shared by the host and gut microflora should now be considered a new player that can be manipulated, using pharmacological and nutritional approaches, to control physiological functions and pathological outcomes. What now remains is to demonstrate the molecular connection between the intestinal microflora and metabolic diseases. We propose here that the proinflammatory lipopolysaccharides play a causal role in the onset of metabolic disorders.

Résumé

Les progrès récents des méthodes de séquençage à ultrahaut débit ont permis de répondre à des questions fondamentales concernant la relation entre la flore intestinale, vecteur de la plus grande diversité génétique de notre organisme, et la physiologie de l’hôte. Il est maintenant établi qu’au cours de l’obésité, du diabète de type 1 et de la maladie de Crohn, pour n’en citer que quelques unes, la flore intestinale joue un rôle important. Ce microbiote peut induire, transférer ou prévenir le développement de ces maladies. Certains acteurs moléculaires responsables de ces effets ont été identifiés et seraient relatifs au contrôle du système immunitaire, du développement vasculaire ou de fonctions endocrines et nerveuses principalement et initialement localisées dans l’intestin. Il faut également considérer que la relation entre l’hôte et la flore intestinale est bidirectionnelle. En effet, certaines données démontrent l’impact de l’hôte sur la flore intestinale. Désormais, une écologie mutualisée entre la flore intestinale et l’hôte doit être considérée comme un nouvel acteur de la physiologie et physiopathologie. Cet acteur peut être manipulé par des approches pharmacologiques et nutritionnelles afin de contrôler la physiologie humaine et ses dysfonctionnements. Les mécanismes moléculaires doivent encore être démontrés. Nous proposons dans cette revue que les lipopolysaccharides bactériens, hautement inflammatogènes, sont responsables de l’initiation du développement des maladies métaboliques.

Introduction

Our human microflora are an inherited feature resulting from our evolution. With the celebration of 200 years since the birth of Charles Darwin, it makes sense to consider that the development of human physiology could be the consequence of environmental factors such as microflora, which might even be thought of as a selection factor among humans. Indeed, the selection of the species comprising our microflora today could be considered to be the result of evolution, with some strains selected on the basis of our evolving genome. This means that the host–microflora relationship could be the result of a bidirectional selection process that has now established a shared ecology among the different members of the microflora and the host.

However, the molecular bases of this ecology and its interaction with the host need deciphering if we are to have access to the potentially vast new spectrum of strategies for the management of human physiology and treatment of diseases. Cancer and the inflammatory and metabolic diseases are among the first in line for the use of microflora-based therapeutic strategies.

Given the wide diversity of our entire body's microflora, this review focuses on the intestinal microflora, and its relationship with metabolic diseases and other related disorders. The choice of this narrow field of discussion is driven by the intuitive concept that feeding our body is also feeding our intestinal flora. Consequently, both the genome and metagenome contribute to the subtle balance of mechanisms involved in metabolism. We discuss here some of the most recent findings on the molecular mechanisms through which the intestinal microflora influence metabolic diseases.

Section snippets

Intestinal microflora: a mutual ecology

The intestine is inhabited by trillions of microorganisms, including bacteria, fungi and the Archaea. Two sets of microorganisms have been described. In one, the tasks performed by some members are partially known and are most likely beneficial to the host. However, the vast majority of species are neither beneficial nor harmful to human physiology, and their function remains completely unknown. These species are termed “normal flora”, or “microbiota”. It is estimated that 500 to 1000 different

Intestinal microflora and inflammatory diseases

The role of the intestinal microflora has been largely described in inflammatory diseases such as IBD, CD and UC. Although beyond the scope of this review, some concepts are helpful for understanding the origin of metabolic disorders. Indeed, it is now thought that obesity and diabetes are associated with a poor inflammatory status, leading to impaired insulin action and adipose tissue plasticity (Fig. 2, Fig. 3) [33], [34]. This means that the origin of metabolic inflammation could have some

Intestinal microflora and T1D

T1D is a T-cell-mediated autoimmune disease that results in destruction of the insulin-producing beta cells of the pancreas. T1D is known as “childhood”, “juvenile” or “insulin-dependent” diabetes, although it is not exclusively seen in childhood, as demonstrated by its growing incidence in adults. So far, there are no preventative measures against T1D, and the initiating cause of the immune-system damage is still not fully understood, although diet and exercise can help. However, a provocative

Intestinal microflora, obesity and type 2 diabetes (T2D)

In the USA, roughly one million diabetic patients are newly diagnosed each year. Given this growing number of cases, as well as the numbers of undiagnosed cases (one-third of patients are not aware of their disease), the treatment of diabetes remains a major therapeutic challenge that the entire population needs to address. Obesity has now been classified as the newest epidemic, as its occurrence is on the increase in Western countries. The World Health Organization (WHO) has estimated that 600

Intestinal microflora and increased metabolic endotoxaemia

A raised hepatic low-density lipoprotein (LDL)–high-density lipoprotein (HDL) ratio defines dyslipidaemia, an important feature of metabolic diseases. The LPS, the principal component of the outer membrane of Gram-negative bacteria and the most powerful of the proinflammatory molecules, is also a component of lipoprotein particles [62], [63]. The latter have been proposed to buffer LPS in response to septic shock [63], and to prevent an overt inflammatory response and fatality. As for the

Antibiotic treatments

As the intestinal microflora could be a causal triggering factor of metabolic diseases, Cani et al. [58] treated control, high-fat-fed and ob/ob mice with broad-spectrum antibiotics. They used ampicillin and neomycin as examples of antibiotics that are poorly absorbed (or unabsorbed in the case of neomycin) by the organism to reduce the occurrence of systemic effects [65]. The results showed that changes in the gut microbiota induced by antibiotic treatment reduced metabolic endotoxaemia and

Microflora as a friend

Mazmanian et al. [93] showed that a specific component of the intestinal microflora can directly interact with the innate immune system of the host, resulting in a beneficial effect. In their elegantly written report, the investigators showed that Bacteroides fragilis can protect animals against experimental colitis induced by Helicobacter hepaticus, a potential pathogenic commensal of the intestinal microflora. The benefit depends on the production of a single specific molecule produced by B. 

Conflicts of interest

The authors have no conflicts of interest to declare in relation to this report.

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