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Discovery of an anti-inflammatory molecule produced by gut bacteria

Researchers at INRA, INSERM, AP-HP, and UPMC have just discovered a new protein with anti-inflammatory properties, which has been named MAM (microbial anti-inflammatory molecule). It is secreted by the bacterium Faecalibacterium prausnitzii and helps fight intestinal inflammation. This discovery, recently published in the journal Gut, is a major advance in efforts to develop new means of treating inflammatory bowel disease. Consequently, the results of this research have great potential future applications.

A few years ago, researchers discovered that the gut bacterium Faecalibacterium prausnitzii was present at lower levels in individuals affected by inflammatory bowel diseases (IBDs), such as Crohn’s disease or ulcerative colitis.They also found that this species secretes one or more molecules with anti-inflammatory properties that help in the fight against IBDs. The identification of the molecules produced by F. prausnitzii is a major step forward, which has occurred thanks to the efforts of a team of researchers from INRA, INSERM, AP-HP (Greater Paris University Hospitals), and UPMC (Pierre-and-Marie-Curie University).

Using biochemistry and mass spectrometry, the researchers discovered the existence of several peptides that were all derived from a single molecule produced by F. prausnitzii, a protein that they called MAM for microbial anti-inflammatory molecule. First, they showed that the addition of MAM to intestinal cells reduced inflammation. Second, they demonstrated that MAM helped alleviate an IBD in a mouse model. More specifically, mice that received MAM lost less weight than control mice. The researchers also showed that MAM’s effect was due to its ability to reduce the levels of certain immune system compounds in the intestinal mucosa that cause inflammation. It therefore seems that the bacteria that live in our guts protect us using the same tools as medical professionals.

When F. prausnitzii is present at low levels, IBDs are exacerbated, creating a vicious cycle. To break the cycle of chronic intestinal inflammation, researchers are working on ways to restore F. prausnitzii’s presence in the gut. These include providing nutritional supplements that contain the bacterium (i.e., probiotics) and/or molecules that promote the bacterium’s growth (prebiotics). The discovery and characterization of MAM also has relevance for the pharmaceutical industry: the protein could eventually be manufactured and serve as an active ingredient in medications. These results, which add to the growing base of knowledge regarding intestinal bacteria, also clearly have practical industrial or medical applications.

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Image en microscopie électronique à balayage de F. prausnitzii © Inra, plateforme MIMA 2, T. Meylheuc

Friday 5 June: World Environment Day

On 15 June 1972, the United Nations celebrated World Environment Day for the first time. Since that day, every year on the same date, the major issues in environmental conservation are given prominence in over 100 countries, a day devoted to the protection of the planet and the future of mankind, which is inseparable from the fate of the ecosystem.

At Inserm, active research is being devoted to understanding the impact of the environment on health, especially changes due to environmental contaminants such as pesticides, atmospheric pollution, radiation, etc.

In 2011 and 2013, the researchers at Inserm endeavoured to understand the influence of  pollution on general health and of environmental factors on reproduction, respectively, in two joint expert reports[1].

Today, many studies are devoted to this theme. The European project HELIX, which brings together experts from every background, is especially focused on exposome-related risk factors for children, i.e., the sum of environmental exposures from the antenatal period on. Pregnancy and the early years of life are well recognised as periods of high sensitivity to these factors, with lifelong consequences.As part of HELIX, Inserm Research Director Rémy Slama directs a working group that is attempting to determine the relationship between the exposome and child health. By establishing a database that includes all environmental pollutants, behaviours, diet and health outcomes, the researchers hope to establish the risk factors that lead to the development of diseases in children.


Cohorte couple-enfants SEPAGES

©Inserm/Delapierre, Patrick. All the photos of the SEPAGES cohort cohorte are available on the Inserm image bank Serimedis



Latest Inserm actualities on this theme:

Air quality in nursing homes affecting lung health of residents – March 2015
Exposure of pregnant women to certain phenols may disrupt the growth of boys during foetal development and the first years of life – September 2014

[1] See the joint expert reports “Reproduction et Environnement” (Reproduction and Environment) and “Pesticides: Effets sur la Santé” (Pesticides: Effects on Health) on the Inserm.fr website.

HIV: new indicators for improving access to treatments for HIV

Despite the recommendations of the World Health Organization (WHO), which advocate early initiation of antiretroviral treatment for people infected with the HIV virus, it has been found that treatment is always initiated too late, particularly in medium- and low-income countries. Thus there is a gap between recommendations and what happens in the field. In a study published in the Bulletin of the WHO, the team led by Dr Dominique Costagliola (Director of the Pierre Louis Institute of Epidemiology and Public Health – Joint Research Unit S 1136 – Inserm/UPMC), in collaboration with the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) sites in Cameroon and Côte d’Ivoire, proposes two new indicators enabling the evaluation of interventions implemented in the field to hasten access to treatments. Particules_VIH

© Inserm/Roingeard, Philippe

Since 2006, the World Health Organization (WHO) has been recommending increasingly earlier treatment for people infected with HIV. In 2006, the threshold for initiation of antiretroviral (ARV) treatment was 200 CD4 cells/mm3, and was then changed to 350/mm3 in 2010, and finally 500/mm3 from 2013. These changes in recommendations have been accompanied by a considerable increase in the numbers of people receiving ARV treatment: this number reached 12.9 million in 2013, including 5.6 million from 2010, leading to hope that the objective set by the United Nations, of 15 million people on ARV treatment by 2015, may be achieved.

However, in Sub-Saharan Africa, initiation of ARV treatment remains late. In 2011, one in two people infected with HIV was started on ARV drugs at a CD4 count below 185/mm3.

Moreover, the delay in treatment represents as much risk for the person infected as for the community. Many studies have in fact shown that on the one hand, rapid initiation of treatment reduces the risk of mortality and morbidity associated with HIV/AIDS for those affected, and on the other hand, reduces the viral load, thereby reducing the risk of transmitting the virus to others. A study conducted in South Africa and published in The Lancet[1] in 2009 went even further by pointing out that elimination of the HIV epidemic might be envisaged if, and only if, those infected with the virus were started on ARV treatment in the year following seroconversion[2].

The crucial question therefore arises regarding the evaluation of policies put in place to improve waiting times for the initiation of treatment. This is what is proposed by the team led by Dr Dominique Costagliola (Director of the Pierre Louis Institute of Epidemiology and Public Health – Joint Research Unit S 1136 – Inserm/UPMC ), which has developed two measurement indicators. The first measures the time elapsed between seroconversion and access to antiretroviral drugs, and the second evaluates the gap between WHO recommendations and what actually happens in the field. Their results are published in the latest issue of the Bulletin of the WHO.

The estimation of these two indicators is based on statistical modelling of data from a survey conducted on the ANRS site in Cameroon in 2011 of people who had started ARV treatment, and on the Côte d’Ivoire ANRS 1220 Primo CI cohort of people for whom the date of seroconversion could be estimated.

The first indicator enables the observation of a reduction, albeit modest, in the mean time from seroconversion to access to ARV drugs: this went from 10.4 years in 2007-2009 to 9.8 years in 2010.

The second indicator, estimating the gap between the WHO recommendations for initiating treatment and the actual time of treatment initiation, has, for its part, increased. It went from 3.4 years for the 2007-2009 period to 5.8 years in 2010.

For Virginie Supervie, an Inserm research fellow in Dominique Costagliola’s team, “These indicators reflect the gap between what needs to be done in theory to end the HIV epidemic, and what is happening in reality.”

They show that substantial efforts are needed.

The United Nations’ eight Millennium Development Goals include action on HIV/AIDS, with the objective of halting its spread and starting to reverse the current trend. However, in the example of the countries chosen for the study, with treatment waiting times of 10 years from seroconversion, and of 6 years from the time of eligibility for treatment, the reality is quite different. The indicators proposed here could contribute to these goals by helping in the evaluation of health policies established in all countries facing the epidemic.

[1] Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for elimination of HIV transmission: a mathematical model. Granich RM1, Gilks CF, Dye C, De Cock KM, Williams BG. Lancet. 2009 Jan 3;373(9657):48-57

[2] Period during which specific antibodies appear in the bloodstream in response to the virus.

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