The almond producers of California have once again treated themselves to the Holy Grail of studies: a randomized controlled trial (RCT). Aim: to evaluate the impact of almonds and of their transformation (ground or not) on intestinal bifidobacteria and, secondarily, on the overall composition of the gut microbiota and intestinal transit time. To do this, 87 adults in good health, avid snackers (crisps, chocolate, etc.) and little inclined to consume fiber (fruit, vegetables, etc.), took part in this 3-arm trial: over 4 weeks, they replaced their 2 usual snacks either by whole almonds (2*23 g/d), or by ground almonds (2+23 g/d) or by 2 muffins with the same calorie content (control).

Almonds: the end of a nutritional myth?

Outcome? Contrary to the main hypothesis, bifidobacteria were not more abundant in the stools of the whole almond (8.7%) or ground almond (7.8 %) groups compared with the control (13.0 %), the opposite was the case. Nevertheless, the slight difference does not withstand an adjustment to the test. Almonds also have no effect on the gut microbiota, intestinal transit time (which the researchers thought was accelerated), stool consistency or intestinal symptoms. The particle size of ground almonds was finer than that of almonds after mastication: for all that, the effect of grinding on the release of lipids and therefore their accessibility by the organism proved smaller than anticipated, to the point that the researchers concluded that the commercial grinding of almonds does not lead to clinically significant differences in terms of nutrient bioaccessibility.
The only significant difference observed: the consumption of almonds (whole and ground) led to an increase in the production of butyrate by the gut bacteria (24.1 μmol/g vs 18.2 μmol/g for the control), a short-chain fatty acid with recognized health benefits, which, according to the authors would suggest a modification of the functions of the gut microbiota. 

No prebiotic effect 

It is without doubt a disappointment for the American producers but, according to this RCT, the consumption of almonds does not exert a prebiotic effect on the fecal bifidobacteria, produce major changes in the microbiota, or affect transit. Could the predominance of women (86.2%) and young people (27.5 ± 6.2 years) in the volunteers have biased the results? Perhaps. In the meantime, other studies are expected targeting a more uniform population to confirm these results. 

It’s all common sense. Often too rich in fat and sugar, the “Western (sidenote: Western diet Diet rich in processed foods, refined sugar, salt, saturated fats (red meats) and trans fats (pastries) Zinöcker MK, Lindseth IA. The Western Diet-Microbiome-Host Interaction and Its Role in Metabolic Disease. Nutrients. 2018 Mar 17;10(3):365.  ) ” diet has an impact on our health. It tends to increase inflammation in the body and to disrupt the metabolism. It can thus lead to obesity, type 2 diabetes, and metabolic syndrome. Numerous studies have shown that the gut microbiota and its immune system play a major role in metabolic balance, with disturbances in the gut converting excess food into extra pounds and serious illnesses.

More fat and sugar means less gut immune cells to balance the metabolism 

To better understand these disturbances, researchers fed mice a diet rich in fat and sugar for four weeks. As expected, in addition to gaining more weight than mice fed normally, these overfed mice also developed a metabolic syndrome (sidenote: Metabolic syndrome Combination of several metabolic anomalies: high blood pressure, large waist circumference, increased blood triglyceride and glucose levels associated to a low blood level of “good” cholesterol. Alberti KG, Zimmet P, Shaw J. The metabolic syndrome--a new worldwide definition. Lancet. 2005 ; 366 (9491) : 1059-62. ) . An analysis of the mice’s gut flora via their droppings showed that this diet caused a rapid loss of segmented filamentous bacteria (sidenote: Segmented filamentous bacteria Segmented filamentous bacteria (SFB) are bacteria of the Clostridiaceae family that colonize the gut of many vertebrate and invertebrate animals without causing an inflammatory response. On the contrary, their presence is thought to stimulate the immune response. They help in the differentiation and maturation of certain defense cells and promote the elimination of pathogenic microbes.  Hedblom GA, Reiland HA, Sylte MJ, et al. Segmented filamentous bacteria–metabolism meets immunity. Frontiers in microbiology. 2018 Aug 24;9:1991.  https://www.frontiersin.org/articles/10.3389/fmicb.2018.01991/full   ) . This in turn reduced the production of T helper 17 (Th17) immune cells (sidenote: T helper 17 (Th17) cells Th17 cells are immune system cells that play a role in host defense against pathogens, particularly at epithelial barriers, such as the gut barrier. Awasthi A, Kuchroo VK (2009) Th17 cells: From precursors to players in inflammation and infection. Int Immunol 21:489–498. ) , subsequent to which the metabolic syndrome appeared. 

The researchers found that Th17 cells regulate the absorption of lipids in the gut and are necessary for protection against metabolic syndrome. The loss of Th17 cells is thus to blame for the adverse health effects of a diet high in fat and sugar. By administering segmented filamentous bacteria to the overfed mice, Th17 production was restored. As a result, the mice lost weight and their metabolism improved.

Sugar, the metabolism’s worst enemy 

But which is most to blame, too much fat or too much sugar? The effects of a diet rich in fat and sugar (including sucrose and maltodextrin, common in candy and soda) were compared with those of a diet rich in fat but low in sugar. The researchers found that sugar on its own modifies the composition of the gut microbiota to the detriment of the segmented filamentous bacteria that stimulate Th17 cells. So would it be enough to eliminate sugar from the diet to ensure protection against metabolic disease? Not entirely, according to the researchers, since protection also requires the presence of the Th17 cells produced by the gut microbiota.

In short, metabolic syndrome, obesity, and type 2 diabetes are the result of complex interactions between diet, the gut microbiota, and immunity. According to the researchers, there is no “universal” diet that would produce the desired effect in everyone. Instead, a personalized approach to metabolic disorders is required. In the future, such approaches could take into account inter-individual differences in the gut microbiota’s immune system.

Vaccines are one of the greatest successes of public health, saving millions of lives worldwide, especially among young children (0-5 years), who are more vulnerable to infectious diseases. However, their efficacy varies from one population to another, with higher rates of protective immunity in European countries than in low- and middle-income countries (LMIC). Since the development of the gut microbiota in early life is intimately linked to the maturation of the immune system, and the microbiota of children in LMIC differ significantly from those of European children, researchers reviewed the evidence pointing to the gut microbiota’s role in disparities in vaccine response.

Immunomodulatory properties

A study on vaccines against tuberculosis, tetanus, hepatitis B, and poliomyelitis in Bangladeshi infants found that the presence of certain taxa is correlated with the rate of vaccine response, positively in the case of Actinobacteria, but negatively for Enterobacteriaceae. In addition, interventions to modify the microbiota (prebiotics, probiotics, antibiotics) provide further evidence of its involvement in vaccine response. A 2018 systematic review summarized the results of 26 studies in humans that used probiotics to enhance the efficacy of various vaccines. The review found positive outcomes in half the studies. Conversely, studies investigating the effects of antibiotics found either no improvement or a reduced immune response, which was attributed to disruption of the microbiota.

Two bacterial genera especially involved 

Two bacterial genera seem particularly capable of modulating responses to vaccines. Bifidobacterium and Bacteroides are essential for the development of a healthy microbiota in young children. However, young children can face significant microbiota disruptions (cesarean section, etc.). The effects of the microbiota on vaccine responses appear to be mediated by certain metabolites and/or cellular components, such as short-chain fatty acids, exopolysaccharides, or extracellular vesicles.

Towards a new generation of vaccine strategies

Although the relevant strains and products need to be better characterized, the intricate relationship between the microbiota and vaccine efficacy opens up rich clinical perspectives. This includes new vaccine stimulation therapies able to improve protection for children from LMIC without the use of adjuvants, which are often thought to have adverse side effects.

Plastic takeaway packaging releases microplastics and nanoplastics that may have a significant impact on the gut and oral microbiota.

Harmful effects on humans remain under-investigated

A study carried out in 2020 showed that plastic food containers made from polypropylene (PP), polystyrene (PS), polyethylene (PE), and polyethylene terephthalate (PET) all contain micro- and nanoplastics. Although the harmful effects of these particles on the microbiota have been demonstrated in animals (fish, shrimp, and mice), until now they have been under-investigated in humans.

Researchers analyzed and compared the gut and oral microbiota of 390 Chinese students aged between 18 and 30 who consumed takeaway food served in plastic packaging either frequently (at least three times a week), occasionally (once a week or less), or never. 

The scientists also created three groups of mice which, for five weeks, were given either a solution of microplastics at 5 mg/ml (20 mice), a solution of nanoplastics at 5 mg/ml (20 mice), or a solution of the same nanoplastics but at 2 mg/ml (20 mice). A control group of 15 mice was also established.

Disruption of microbial balance

The results show that consumers of takeaway food in plastic containers more frequently suffer from gut disorders and coughs than those who never consume such food. They also presented a dysbiosis of the gut and oral microbiota with specific bacterial signatures. The gut microbiota of occasional consumers was strongly associated with the presence of Faecalibacterium, while that of heavy consumers was associated with Collinsella. For the oral microbiota, the bacteria most strongly associated with heavy consumers was Thiobacillus.

Significant impact even with smaller particles and at low doses

The study on mice showed that all the animals fed with plastic particles presented a gut dysbiosis when compared to the control group. Changes in the size (i.e. micro- vs. nanoplastics) or quantity (5 mg/ml vs. 2 mg/ml) of the particles ingested had no effect on their impact.

Moreover, the researchers believe that the recurrent cough in takeaway lovers may mean that micro- and nanoplastics are able to migrate from the gut to the lungs, where they accumulate in the airway microbiota, causing a dysbiosis that leads to the cough. Although yet to be confirmed, these results are one more reason to switch to a glass lunch-box.

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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