In theory, vaccines work on a simple (or fairly simple) principle: they train our immune system (composed of an army of antibodies) to react quickly to attacks by invading pathogens. (sidenote: To do this, a harmless fragment of the invader is inoculated into the host so that it develops targeted defenses. When the real pathogen subsequently appears, our defenses are ready to neutralize it.  https://www.who.int/news-room/feature-stories/detail/how-do-vaccines-work ) However, in practice, vaccines do not always work. They save millions of lives each year, especially among young children who are more vulnerable to infectious disease, but they are more effective in European children than in children from low- and middle-income countries (LMIC). Although treated with vaccines, many of these children fail to develop protective immunity. (sidenote: While nearly 100% of Finnish children develop protective immunity in response to rotavirus vaccines, this is the case for only 58% of children in Nicaragua and 46% of children in Bangladesh. Similarly, protection rates for the BCG vaccine range from 0%-51% in African children versus 88%-100% in European children. ) In other words, the army of antibodies that makes up their immune system (sidenote: Innate and adaptive immunity  The human body protects itself using two kinds of defense mechanisms: innate immunity and adaptive immunity. Innate immunity is the first line of defense against disease agents and is an immediate response, while adaptive immunity is delayed but provides lasting protection Janeway CA Jr, Travers P, Walport M, et al. Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; 2001. Principles of innate and adaptive immunity. ) fails to respond. Untrained to recognize and eradicate the enemy, they are unlikely to be able to defend the host in a real battle. But what causes this “immune inequality”?

Gut microbiota, an ally of immune response

The answer may involve a special third force allied with the immune army, the gut microbiota. The development and functioning of the gut microbiota and immune system are intimately linked; but the gut microbiota of European children differs significantly from that of children from LMIC. The researchers thus believe that differences in microbiota composition may explain variations in vaccine response. Accordingly, certain studies have sought to modify the gut microbiota in order to improve immune response. Trials in humans that used probiotics (live bacteria that strengthen the microbiota) to increase the proportion of patients who develop protective immunity have shown positive outcomes in half of cases. Two sentries of the gut microbiota, the bacterial genera Bifidobacterium (sidenote: Bifidobacterium A genus of Y-shaped bacteria, most species of which are beneficial to humans. They are found in the gut of humans, and in some yogurts.

They:
- Protect the gut barrier 
- Participate in the development of the immune system and help fight inflammation 
- Promote digestion and improve symptoms of gastrointestinal disorders Sung V, D'Amico F, Cabana MD, et al. Lactobacillus reuteri to Treat Infant Colic: A Meta-analysis. Pediatrics. 2018 Jan;141(1):e20171811.  O'Callaghan A, van Sinderen D. Bifidobacteria and Their Role as Members of the Human Gut Microbiota. Front Microbiol. 2016 Jun 15;7:925. Ruiz L, Delgado S, Ruas-Madiedo P, et al. Bifidobacteria and Their Molecular Communication with the Immune System. Front Microbiol. 2017 Dec 4;8:2345. ) and Bacteroides, seem particularly capable of rallying the immune system’s troops.

Improving vaccine response

Although further research is required, the researchers are already considering new vaccine strategies that involve the modulation of gut flora composition in the hope of stimulating responses to vaccines. This new approach may increase access to effective vaccines in low- and middle-income countries (LMIC). It may also make it possible to do without certain adjuvants that are added to boost immune responses, but which are thought to have adverse side effects that fuel vaccine hesitancy.

Only half an hour to eat? Think twice before grabbing fried noodles at your local snack bar... especially if they come in plastic packaging. According to a recent study, the microplastics and nanoplastics in these disposable containers may disrupt your gut and oral microbiota.¹

Microbiota imbalance: plastic in the dock

We know that takeaway food packaging releases significant amounts of small plastic particles. Tests on animals fed with these micro- and nanoplastics show an adverse impact on the animals’ gut microbiota. But how do they affect human health?

To answer this question, researchers enrolled 390 Chinese students aged between 18 and 30 and put them into three groups: heavy consumers of takeaway food in plastic packaging (at least three times per week), occasional consumers (maximum once per week), and non-consumers. They collected stool and saliva samples in order to analyze and compare their oral and gut microbiota.

Significant impact on balance of gut and oral flora

The results show that consumers of takeaway food in plastic containers suffer more gut disorders and cough than those who never consume such food. More worryingly, they show significant alterations (dysbiosis (sidenote: Dysbiosis Generally defined as an alteration in the composition and function of the microbiota caused by a combination of environmental and individual-specific factors. Levy M, Kolodziejczyk AA, Thaiss CA, et al. Dysbiosis and the immune system. Nat Rev Immunol. 2017;17(4):219-232.   ) ) in their gut and oral microbiota. These have specific bacterial signatures, such as higher quantities of Collinsella in their stools and higher quantities of Thiobacillus (previously found in rice fields polluted by plastic) in their mouths.

Particles able to pass between body compartments?

The authors suggest that coughing, which was more frequent in the takeaway food eaters, may result from micro- and nanoplastics that migrate from the gut to the lungs, where they accumulate in the airway microbiota, leading to dysbiosis. 

These results have yet to be confirmed, but in the meantime, consider preparing your own snacks and, above all, carry them in a (more stable) glass container.

Identify early and intervene as soon as possible. This is the key to managing neonatal necrotizing enterocolitis (NEC), which affects between 5% and 12% of premature babies. However, due to a lack of sufficiently sensitive biomarkers in newborns, this remains wishful thinking. Nonetheless, previous studies have shown the appearance of a gut dysbiosis in the 7 days to 72 hours preceding NEC. Can the microbiota and its metabolites – particularly short-chain fatty acids (SCFAs) involved in maintaining the integrity of the intestinal epithelium – predict NEC?

34 preterm infants with digestive disorders

To explore the predictive value of the gut microbiota and SCFAs, a prospective study was conducted in 34 preterm infants (gestational age less than 34 weeks) suffering from gut disorders (bloating, vomiting, or bloody stools). 17 of the infants were suspected of having NEC and 17 were matched controls without NEC whose stools were collected on the enrollment day. Of the 17 infants suspected of having NEC, the diagnosis was confirmed in only 12 (sidenote: Gut perforation The remaining 5 children showed gut perforation on the day of enrollment in the study. ) (a subgroup of the original matched sample), whose stool was collected seven days later on average.

Gut dysbiosis precedes NEC

Contrary to the results of previous studies, the researchers did not systematically observe a loss of gut diversity prior to the disease: some indices of bacterial richness (Ace and Chao1) showed a significant difference, while others (Simpson and Shannon) did not. According to the authors, the digestive disorders present in all children in the study (including the controls) may explain this discrepancy with the data from the literature.

Conversely, seven days before the onset of NEC, a change in the composition of the flora was noted: the bacterial species Streptococcus salivarius and Rothia mucilaginosa increased, while Bifidobacterium subsp. lactis decreased. Variations at phylum level (increase in Proteobacteria, decrease in Firmicutes, Actinobacteriota, and Bacteroidota) were also explored, but the differences were not deemed significant.

Three SCFAs as metabolic markers

The researchers also looked at bacterial metabolites, specifically acetate, propionate, and butyrate, which represent 90%-95% of total SCFAs in the human gut. The study showed that these three SCFAs decreased significantly seven days before the onset of NEC, probably due to the decrease in Firmicutes and Bacteroidota. These metabolites proved to be much better predictive biomarkers for NEC than the bacterial biomarkers. More specific and sensitive (AUC of 68%-73%, depending on the SCFA), in the future they may have a clinical application.

Road transport, factories, wood heating... It has long been known that air pollution adversely affects lung and cardiovascular health. Indeed, recent studies have shown that it alters the microbiota of adults. But what impact do air pollutants have on the microbiota of babies?

To answer this question, scientists from the University of Colorado Boulder (USA) measured air pollutant exposure levels in 103 Californian children aged six months. They also collected stool samples to analyze the composition of their microbiota.

^{Sources (sidenote: WHO. https://www.who.int/news-room/spotlight/how-air-pollution-is-destroying-our-health/10-things-to-know-about-air-pollution )}

Serious microbiota disturbances

The scientists found that, after adjusting for potential confounders such as birthweight, socioeconomic status, mode of delivery, and breast or formula feeding, the more newborns are exposed to air pollution, the greater the changes to the composition of their microbiota.

The microbiota of the most exposed babies contained more Dialister and Dorea, two bacterial genera associated, in adults, with systemic inflammation and a higher risk of cancer, multiple sclerosis, and mental health disorders.

Their microbiota also contained fewer bacteria that produce short-chain fatty acids (SCFAs (sidenote: AGCC Acides gras à chaîne courte ) ), which are known to have beneficial effects on gut barrier integrity, cardiovascular health, gut-brain communication, and the blood-brain barrier (sidenote: Blood-brain barrier The blood-brain barrier is a “physical” barrier that separates the central nervous system (CNS) from the bloodstream. It tightly controls exchanges between the blood and the brain compartment. 
Engelhard HH, Arnone GD, Mehta AI, Nicholas MK. Biology of the blood-brain and blood-brain tumor barriers. InHandbook of Brain Tumor Chemotherapy, Molecular Therapeutics, and Immunotherapy 2018 Jan 1 (pp. 113-125). Academic Press. https://www.sciencedirect.com/science/article/pii/B9780128121009000085 ) . 

Understanding the effects of pollution on microbial communities

This study highlights for the first time an association between exposure to ambient air pollution and the gut flora composition of young children. Although concerning, these results still need to be confirmed and completed by further studies. As a next step, researchers should follow changes in the children’s microbiota over time, try to identify the mechanisms by which pollution exerts its effects on microbial communities, and find out whether the changes are really associated with health problems.

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For scientists, an “association” is where two phenomena occur at the same time, without necessarily having a cause-and-effect relationship. Is the gut dysbiosis (i.e. imbalance of the gut flora’s composition) observed in those infected with human immunodeficiency virus (HIV) a cause or a consequence of the disease? Or is it both? With only a few days to go before World AIDS Day on December 1st, the jury is still out, since the state of the gut microbiota prior to infection is not well known, and many other factors influence the appearance of dysbiosis, including age, diet, antibiotic use, and even sexual behavior, according to some recent data^2,3.  

To get a clearer picture, US researchers brought together gut microbiota samples from about 50 men who have sex with men, collected during different studies. They selected individuals with similar profiles (age, ethnicity, sexual behavior, etc.), half of whom were infected with HIV during the course of the studies, with the other half remaining HIV free. They were thus able to compare the gut microbiota of the infected men before and immediately after infection, and to compare the infected men’s gut microbiota with that of the healthy uninfected pairs.

_Sources

Minimal changes in microbiota before/after HIV infection... 

The authors first found that the composition of the infected men’s gut microbiota changed very little during the acute phase of HIV. Only increased Fusobacterium mortiferum was observed. Not normally resident in the gut flora, this bacterial species had already been associated with HIV in other studies.

... but significant pre-infection differences vs. controls

In contrast, the gut microbiota of the men who would go on to be infected with HIV (i.e., their “pre-infection” gut microbiota) differed from that of the controls (who remained HIV free). In particular, they had fewer bacteria from the Bacteroides group, and increased levels of Megasphaera elsdenii, Acidaminococcus fermentans, and Helicobacter cinaedi. This type of dysbiosis has frequently been observed in HIV-infected individuals. However, in this new study, the gut imbalance appears to have been present before infection, potentially influencing susceptibility to HIV, according to the authors.

Gut microbiota, a new tool for preventing HIV?

So, does gut microbiota composition play a role in susceptibility to HIV infection? Encouraged by similar conclusions from another US team⁵, the researchers propose that this avenue be followed up by studies on larger samples. They hope that this will identify a “gut microbiota signature” associated with greater susceptibility to HIV infection, thus allowing more targeted prevention via treatment of the gut microbiota of people at risk.⁶  

The researchers make it clear that this finding does not contradict the idea that HIV can itself cause dysbiosis. The short duration of the study meant it was not possible to observe the changes in gut microbiota composition that occur during chronic HIV. In addition, these results were obtained in a small group with a specific profile and thus generalizability beyond this population is limited.

With only a few days to go before World AIDS Day on December 1st, let’s take a look at the links between HIV and the microbiota. Numerous studies have associated changes in the gut microbiome with HIV infection. However, many of these studies have been cross-sectional and methodologically heterogeneous, and therefore subject to various confounding factors. HIV infection is known to be accompanied by gut dysbiosis and bacterial translocation linked to systemic inflammation, but the time course involved is not fully understood. Furthermore, recent studies have shown that, in addition to age, diet, and antibiotic use, sexual behavior also influences the gut microbiota, regardless of HIV status^2,3, further confounding the evidence.

Longitudinal study with bias controlled

 To measure changes in the gut microbiota and markers of inflammation during HIV infection, the researchers selected fecal and blood samples from four different longitudinal studies (USA, Peru) conducted over periods of 4 months to 2 years among men who have sex with men. Of these men, 27 were infected with HIV. The samples from the infected men were paired with those of 28 controls with similar demographic and behavioral characteristics.

Changes in the gut microbiota and inflammatory markers precede seroconversion 

The researchers noted few changes in the gut microbiota of subjects during the acute phase of HIV. In a subgroup from a US study, only an increase in Fusobacterium mortiferum was observed shortly after seroconversion, together with a decrease in Prevotella intermedia. The most significant differences were between pre-HIV infection subjects and controls. The gut microbiota of pre-HIV infection subjects showed reduced levels of several Bacteroides species and a higher level of Megasphaera elsdenii. They also had higher plasma levels of inflammatory cytokines (B cell activating factor, IL-8, TNF-α).

Gut microbiota, a targeted prevention option?

According to the authors, the study suggests that the changes to the gut microbiota existed before HIV infection. Together with similar results from another US team⁴, this shows that gut dysbiosis is a contributing factor to HIV rather than a consequence of it, even if dysbiosis is subsequently observed in chronic HIV. The observation period of the study was too short for the researchers to identify subsequent changes. In addition, the small sample size and the specific characteristics of the participants (sex, age, drug use, sexual behavior, etc.) may also limit generalizability. However, the researchers believe that the discovery of a gut signature for HIV susceptibility and/or inflammatory markers may provide a new tool for targeted prevention.

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The gut microbiota interacts with the central nervous system and is involved in numerous diseases, including mental illnesses. It determines the way the body adapts and responds to its environment, which may include our responses to alcohol consumption. Some people seem to enjoy and/or tolerate alcohol more than others, while others are more prone to abuse and addiction. Spanish researchers have explored the links between the gut microbiota and behavior towards alcohol in humans and animals.

_Sources

Gut microbiota and transit modified in heaviest drinkers

The researchers used a questionnaire to assess the weekly alcohol consumption in grams of 507 students (83.3% female, mean age 19.8 years), taking into account the type and amount of alcohol consumed, the time elapsed between 2 drinking episodes, and the subject’s weight. The appearance of the participants’ feces was classified according to the Bristol scale. While nearly 55% had type 3 stool, the heaviest drinkers tended to have type 1, with a linear relationship between stool type 1 and alcohol consumption. This result was unexpected, since alcohol abuse is usually associated with diarrhea. To study the effect of alcohol consumption on the composition of the gut microbiota, the researchers analyzed fecal samples from the 17 non-drinkers in the cohort and from the 17 heaviest drinkers. Alpha diversity (sidenote: α diversity A measure indicating the diversity of a single sample, i.e. the number of different species present in an individual. Hamady M, Lozupone C, Knight R. Fast UniFrac: facilitating high-throughput phylogenetic analyses of microbial communities including analysis of pyrosequencing and PhyloChip data. ISME J. 2010;4:17-27. https://www.nature.com/articles/ismej200997 ) did not differ significantly between the two groups, but beta diversity (sidenote: β diversity A measure indicating the species diversity between samples, it allows to assess the variability of microbiota diversity between subjects. Hamady M, Lozupone C, Knight R. Fast UniFrac: facilitating high-throughput phylogenetic analyses of microbial communities including analysis of pyrosequencing and PhyloChip data. ISME J. 2010;4:17-27. https://www.nature.com/articles/ismej20099 ) showed a greater abundance of Actinobacteria in the heavy drinkers.

Rats receiving a transplant develop a taste for alcohol

The researchers then induced alcohol dependence in 8 rats via intragastric administration of alcohol for ten days, until signs of withdrawal appeared. Fecal samples were taken from these animals and transplanted into recipient rats. Two weeks later, the voluntary alcohol consumption among the latter was 27.4% higher than among controls. This time-lapse suggests that the new microbiota is the cause, rather than a consequence, of increased alcohol consumption. A gut microbiota analysis in the alcoholic donor and recipient rats suggests that the genus Porphyromonas, which was significantly less abundant in these animals than in controls, may be associated with the urge to consume alcohol. The researchers did not find any bacterial genus with increased content, but noted that in other studies, Actinobacteria were more abundant in alcoholic mice, just like they are in humans.

They believe the implanted microbiota to be a predisposing factor: when alcohol is added, this new microbiota somehow favors the abundance of bacteria that benefit the most from alcohol consumption. Moreover, given the observed reduction in locomotor activity in the recipient rats, the implanted microbiota may also modify their behavior towards alcohol by influencing cerebral dopaminergic neurotransmission and the brain’s reward system.

Managing alcohol use disorders via the microbiota

To conclude, the authors believe that this study supports a link between the gut microbiota and alcohol consumption. Furthermore, treating the gut microbiota with probiotics and/or prebiotics may help manage alcohol use disorders. The relevant genera and species have yet to be determined.