Alzheimer’s disease is recognized as being multifactorial: genetics, lifestyle and environment are all involved. But according to a study published in the journal Brain ¹ in October 2023, it seems that the intestinal microbiota also plays a role. And an important one at that: simply transplanting the intestinal microbiota of patients with Alzheimer’s disease into juvenile rats is enough to induce alterations in the animals' spatial memory, a typical symptom of the disease.

An unbalanced intestinal microbiota

It was already known that patients with Alzheimer’s disease have an altered intestinal microbiota. The authors reconfirm this observation, with, for example, a reduction in Coprococcus bacteria, associated with healthy aging, in patients.

But above all, they show that these changes are associated with the clinical condition of patients, and more specifically with their success in a test of cognitive and memory capacity called MMSE: the more certain bacteria recognized as beneficial to health are present, the higher the MMSE score; conversely, the abundance of deleterious bacteria (Desulfovibrio, for example) goes hand in hand with a deterioration in the MMSE score. Thus, intestinal bacteria are associated with patients’ cognitive performance.

A transfer of intestinal flora... and disease

But how do we understand this link between the gut and the brain? Does the intestinal microbiota contribute to Alzheimer’s disease, or is it also affected by the disease?

To answer this question, the team took stool samples from healthy donors and Alzheimer’s patients and transplanted them into young adult rats. The result: in rats that received the "Alzheimer’s" flora, the abundance of deleterious Desulfovibrio bacteria increases, the digestive system is altered (wetter stools, shortening of the colon, etc.) and, above all, the rats perform less well in exercises requiring their long-term spatial memory. In other words, symptoms comparable to those of humans affected by the disease.

Further experiments suggest that transplantation altered a process in these rats that enables them to produce new neurons. How can what happens in the digestive tract reach the brain? Probably via the bloodstream: an unbalanced intestinal microbiota produces small molecules capable of crossing the blood-brain barrier and jeopardizing neuroregeneration processes.

The Biocodex Microbiota Institute is made of a passionate, enthusiastic, skillful and motivated team of scientific communication experts, journalists, digital marketers but also trainees dedicated to providing information about microbiota and promoting its importance to everyone. To fulfill this mission, we are supported by eminent microbiota experts coming from 27 nationalities.

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More than 230 researchers and healthcare professionals across diverse disciplines have been collaborating with the Biocodex Microbiota Institute since its creation in 2017. All together, we join forces and skills to advance microbiota research (gut microbiota but also vaginal, skin, lung…) and raise awareness about its crucial role.

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Scientific integrity drives the Biocodex Microbiota Institute. Once a month, the Institute’s editorial committee selects a range of scientific publications for a weekly news publication.

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International Microbiota Observatory. The Biocodex Microbiota Institute commissioned Ipsos to conduct a major international survey of 6,500 people in 7 countries (France, Spain, Portugal, U.S., Brazil, Mexico and China) to better understand people’s knowledge and behavior with regard to their microbiota. Check out the results.

IBS, endometriosis, overweight, Alzheimer’s disease, Parkinson’s disease, anxiety disorders, cancer, but also antibiotic resistance… Many health issues and concerns related to microbiota transcend national boundaries and require collaboration between researchers, patients’ associations and medical societies from across the world. That’s the reason why the Institute is endorsed by worldwide medical societies and patients ‘associations such as:

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Gut microbiota may be involved in Alzheimer’s disease. This is evidenced by specific alterations in gut flora in patients and in mouse models. But are these changes in gut microbiota the cause or a symptom of the disease? Research published in Brain ¹ provides some answers.

Altered cognitive state and microbial signature 

The 64 Alzheimer’s patients included in the study showed increased systemic inflammation compared with 69 healthy subjects. Their microbiota is enriched in Bacteroidetes (which includes many pro-inflammatory species) and depleted in Firmicutes and Verrucomicrobiota (known to be beneficial). Clostridium sensu stricto 1 and Coprococcus, producers of short-chain fatty acids, are less present, while the abundance of the pathobiont Desulfovibrio is increased.

These alterations in gut microbiota have been shown to be associated with the clinical state of patients with Alzheimer’s, and in particular with MMSE (Mini-Mental State Examination) cognitive and memory assessment scores: the less Coprococcus present, the lower the MMSE score; the more abundant Desulfovibrio and Dialister, the worse the MMSE score. These results point to a microbial signature of impaired cognitive performance in Alzheimer’s disease.

FMT modifies colonic function...

All that remained was to understand the contribution of human gut microbiota to Alzheimer’s disease. To do this, the team transplanted fecal samples from Alzheimer’s patients and healthy subjects into young adult rats with microbiota depleted by 7 days of antibiotics. While taxon diversity is maintained in rats that received healthy flora, FMT of microbiota from an Alzheimer’s patient induces a greater change in taxa, with a particular increase in Desulfovibrio. The colonic function of rats that received the microbiota of an Alzheimer’s patient was also modified (wetter stools, shortening of the colon, crypt hyperplasia of the proximal colon...).

...and transfers memory impairment

Above all, rats that received the microbiota of an Alzheimer’s patient performed less well on certain tasks, notably those involving long-term spatial memory and physiologically dependent on neurogenesis, the process by which neural stem cells in the hippocampus generate new neurons throughout life. Moreover, the authors show that FMT of microbiota from an Alzheimer’s patient affects this neurogenesis, and in particular the survival and dendritic arborization of neurons. How? Probably via the vascular route. The authors point at certain bacterial metabolites capable of crossing the blood-brain barrier. The authors also show that in vitro, bathing embryonic hippocampal progenitor cells in serum from Alzheimer’s patients affects neuronal proliferation, differentiation and dendrite morphology. 

These results, which need to be confirmed by other studies (mechanistic, interventional, metabolomic, etc.), show that Alzheimer’s disease is not confined to the brain alone. They could inspire new approaches aimed at delaying the onset or slowing the progression of dementia, or even be applied to other neurodegenerative and cognitive disorders.

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Tell me what your microbiota looks like, and I’ll tell you how the Covid vaccine protects you. 

That’s the takeaway from a study ¹ published last September in the academic journal Signal Transduction and Targeted Therapy.

The researchers succeeded in demonstrating that the presence of certain bacteria and molecules in the gut prior to the first injection may reinforce the immunity conferred by the vaccine, thereby extending its duration of action. 

A promising avenue for the development of new adjuvants.

• 161 participants
• two Covid-19 vaccines
• six months follow-up

This finding was made thanks to the participation of 161 volunteers enrolled for six months. 

121 participants received two injections of Comirnaty, Pfizer-BioNTech’s mRNA vaccine, while the remaining 40 received CoronaVac, Chinese firm Sinovac Biotech’s inactivated virus vaccine. No volunteers were infected with Covid during the study. Immediately prior to vaccination, then one month and six months later, the researchers took the following samples from the participants:

• blood samples to measure antibody concentrations; 
• stool samples to identify the bacteria in their gut microbiota and measure the levels of substances produced by the subject and their bacteria (vitamin B3, GABA, fumaric acid, etc. – i.e., the renowned “metabolome”).

The researchers found, first of all, that Comirnaty achieves better immunity than CoronaVac. 

State of gut flora modulates vaccine-induced immune response

In the Comirnaty group, patients whose gut microbiota before the first injection was abundant in bacteria such as Bacterium adolescentis, 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. ) bifidum and Roseburia faecis had higher levels of SARS-CoV-2 antibodies in their blood six months later. The same type of stronger, longer-lasting immunity was found in those with a metabolome richer in vitamin B3 and GABA.

In the CoronaVac group, a low abundance of Faecalibacterium prausnitzii and a higher abundance of Phocaeicola dorei – a signature found in Covid-infected patients – was associated with better immunity at six months, as was a higher presence of fumaric acid in the metabolome, a compound known to hinder virus replication.

Another finding was that, for the Comirnaty group, a greater proportion of the bacterial strains in the microbiota altered by the vaccine had not recovered their pre-vaccination state when compared with the CoronaVac group. While it remains difficult to analyze the consequences, the researchers point out that some of the strains affected are the same as those found altered in people suffering from long Covid.

Immune responses to the Covid-19 vaccine depend on multiple factors, among them gut microbiota composition. At the same time, vaccination may in turn modulate gut flora. To better understand this bi-directional interaction, a prospective longitudinal study was carried out in Hong Kong. Blood and stool samples were collected (at baseline and then at one and six months post-vaccination) from subjects vaccinated with either BNT162b2 (sidenote: BNT162b2 Covid-19 vaccine comprising lipid nanoparticle-encapsulated mRNA, developed by Pfizer-BioNTech and marketed under the name “Comirnaty” in the EU. ) (121 subjects, mean age 42 years) or CoronaVac (sidenote: CoronaVac Covid-19 vaccine developed by Sinova comprising whole inactivated and adjuvanted (adjuvant: aluminum hydroxide) virus. Approved in many countries in Asia and South America. In Europe, it has been approved in Bosnia, Ukraine, and Turkey. Source: www.mesvaccins.net/ ) (40 subjects, mean age 55 years) who did not contract Covid during the study.

Effect of microbiota on vaccine response

The immunogenicity of BNT162b2 (mRNA vaccine) was stronger and longer lasting than that of CoronaVac, with subjects showing higher antibody levels at six months.

In subjects vaccinated with BNT162b2, a higher content of Bifidobacterium adolescentis, B. bifidum, and Roseburia faecis at the time of vaccination was associated with a better vaccine response. The abundance of three bacterial species (B. adolescentis, Lachnospira pectinoschiza, and Lactococcus lactis) at baseline even predicted vaccine response at six months. Twenty-eight metabolites, including nicotinic acid (Vitamin B) and γ-aminobutyric acid (GABA), were positively or negatively associated with vaccine response.

In those who received CoronaVac (inactivated virus), more antibodies at six months were associated with more short-chain fatty acid-producing bacteria such as Phocaeicola dorei, Blautia massiliensis, and Dorea formicigenerans and a lower abundance of Faecalibacterium prausnitzii at baseline. The abundance of three bacterial species (Clostridium fessum, Actinomyces sp. ICM47, and Enterocloster citroniae) at baseline predicted antibody titles at six months. Forty-two metabolites, including L-tryptophan, were found to be negatively associated with antibody titles at six months. Thus, each vaccine technology is associated with a particular immune response, depending on initial microbiota composition.

Effect of vaccine on microbiota

At the same time, both vaccines altered the gut microbiota: reduced diversity; increased content of Bacteroidota and Pseudomonadota, decreased content of Bacillota and Actinomycetota; depleted histidine biosynthesis pathways, increased methionine and arginine degradation pathways. Alterations to the gut microbiota associated with CoronaVac vaccination more closely resembled those induced by SARS-CoV-2 infection. The technology used in CoronaVac (inactivated whole virus) may explain this difference.

Lastly, the gut microbiota of the BNT162b2 group recovered its diversity more quickly, but a greater proportion (58.0%) of the species modified by vaccination had not returned to initial levels at six months post-vaccination compared with CoronaVac (21.6%).

Osteomicrobiology is a new research field aiming at exploring the mechanisms linking the gut microbiota and the skeleton, and looking into many hypotheses about the mechanisms involved. For example, the gut flora may stimulate certain white blood cells, thus inducing inflammation, which in turn leads to bone loss. Numerous other mechanisms have been put forward, some involving short-chain fatty acids (sidenote: Short chain fatty acids (SCFA) Short chain fatty acids (SCFA) are a source of energy (fuel) for an individual’s cells. They interact with the immune system and are involved in communication between the intestine and the brain. Silva YP, Bernardi A, Frozza RL. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol (Lausanne). 2020;11:25. ) produced by bacteria via fermentation of fibers in the colon, or dietary compounds such as vitamins K or D. However, large-scale studies are still lacking. Or rather, were lacking, since a study on more than 2,000 Americans has provided new evidence.

Bone health: two bacteria under the spotlight

The study included participants from two markedly different studies: 836 elderly men (average age 84.2) on the one hand, and 1,227 men and women in their fifties (average age 55.2), on the other. Despite this heterogeneity of profiles in terms of age and sex, two bacteria, Akkermansia and Clostridiales DTU089, seem to be systematically associated with poorer bone health, and therefore a higher risk of osteoporosis (sidenote: Osteoporosis A disease characterized by a reduction in bone mass and a breakdown in the structure of bone tissue. It makes bones more fragile and thus considerably increases the risk of fractures. Source: Inserm ) and fracture at the slightest trauma. These bacteria are more abundant in those with low levels of physical activity and very limited protein intake – two behaviors not recommended for maintaining bone health.

Conversely, gut flora rich in Lachnospiraceae and Faecalibacterium were associated with stronger shins. It thus seems that certain bacteria influence how our bones remodel themselves as the years go by. Although this hypothesis has yet to be confirmed.

Sun, exercise, and a balanced diet

This finding is merely preliminary. Further studies are required, in particular to better understand the mechanisms by which certain bacteria can influence the integrity of our skeleton. This holds out the major hope of one day being able to modulate our gut microbiota to better protect bone health.

In the meantime, time spent outdoors (the sun pushes the body to produce vitamin D, which in turn facilitates calcium absorption), regular exercise, and a balanced diet will all help preserve bone health as you get older.

A number of mechanisms have been put forward to explain a link between the digestive microbiota ¹, from mouth to rectum, and atherosclerosis such as interference with lipid metabolism, inflammation linked to bacterial translocation or bacterial metabolites... However, studies to date have been hindered by multiple limitations (interactions with patient treatments, lifestyle, etc.). These biases have been partly overcome by a Swedish multicenter study involving 8,973 members of the SCAPIS ² cohort aged 50 to 65 with no history of atherosclerosis. Oral and fecal microbiota samples were collected and analyzed, then coronary atherosclerosis was measured using a Coronary Artery Calcium Score (sidenote: Coronary Artery Calcium Score quantitative assessment of the extent of calcified atheromatous deposits on the walls of the coronary arteries, i.e. the arteries of the heart. Higher Coronary Artery Calcium Scores mean greater cardiovascular risk. Source : CHversailles   ) and an angiography. Although asymptomatic, 40.3% of participants had coronary calcification, and 5.4% at least one stenosis with an occlusion exceeding 50%.

64 gut and oral species involved

The composition and diversity of the digestive microbiota were found to be associated with subclinical atherosclerosis. 64 species were associated with the Coronary Artery Calcium Score: 51 were harmful (the strongest associations being observed for Streptococcus anginosus and Streptococcus oralis subsp oralis) while 13 were protective. 

Of the 64 species, 19 were associated with markers of inflammation (C-reactive protein), including streptococci and other oral cavity species, and 16 with markers of infection (neutrophil count). According to the authors, many of these bacterial species (S. anginosus, S. oralis subsp oralis, S. parasanguinis, S. gordonii) are capable of crossing the oral or gut barrier during dental care or due to lesions, and then infecting coronary valves and vessels (infective endocarditis).

From digestive dysbiosis to atherogenesis

The composition of the gut microbiota may also contribute to atherogenesis through the alteration of host metabolism. Gut microbial species common to the oral cavity (e.g. all Streptococcus spp associated with coronary calcification, Rothia mucilaginosa, Bifidobacterium dentium, and Ligilactobacillus salivarius) were associated with lower plasma levels of indole propionate (considered protective against atherosclerosis) and higher levels of microbiota-derived plasma metabolites such as secondary bile acids and imidazole propionate (pro-inflammatory). 

While further longitudinal and experimental studies remain necessary, this work provides evidence of an association between the composition of the digestive system’s microbiota (notably Streptococcus spp and other species also present in the oral cavity), coronary atherosclerosis, and markers of systemic inflammation.

New research ¹ reveals that the age-old adage “an apple a day, keeps the doctor away” also applies to nourishing our microscopic inhabitants - the gut microbiome. Scientists discovered that plant- associated bacteria migrate to and persist within the human digestive tract. This study represents the first evidence for the transmission of plant microbes to the gut via consumption.

Plant microbes hitchhike to colonize gut microbiota

The scientists from The Institute of Environmental Biotechnology ² in Austria performed a sophisticated computational genomic analysis, reconstructing 156 bacterial genomes from fruit and vegetable metagenomic datasets. These microbial DNA sequences served as a reference to detect fresh produce-derived bacteria within publicly available human stool metagenomes. The researchers also examined a longitudinal cohort tracking infant stool samples over three years to assess bacterial persistence.
Researchers were surprised to find common bacterial genera inhabiting both fresh produce and people's intestines. Core plant genera detected in subjects' guts included Enterobacterales, Burkholderiales and Lactobacillales.

Plants seed 2% of total gut bacteria  

On average, nearly 2% of an individual's unique gut bacteria originated from fruits and vegetables. This proportion increased in younger kids and with greater vegetable intake.

Even if this proportion remains low compared to the total bacterial community, these plant-derived bacteria provide essential health components such as short-chain fatty acids, vitamin B12 and vitamin K. Their minority abundance belies a major functional role– supplementing human genes and metabolism.

Finally, the study showed that eating over 10 different plants weekly, compared to less dietary diversity, was associated with heightened gut species richness. Regular vegetable consumption was also linked to a more heterogeneous bacterial community structure.

Soil seeding our microbiome future

As human activity shrinks natural ecosystems and depletes environmental bacteria, dwindling microbial input from fresh produce may have far-reaching public health consequences we have only begun to grasp.

This research spotlights produce's unsuspected significance as vital conduits seeding our gut ecosystem - and suggests plant and soil conservation may "sow" seeds for better global microbiome futures.

We can also argue that diminishing microbial input from intensively farmed, less microbiome-rich produce may have negative public health impacts. This spotlight on fruits and vegetables as vital but vulnerable conduits transmitting environmental bacteria to our guts carries urgent implications for agriculture, conservation, and medicine.

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We've all heard "an apple a day keeps the doctor away." But what if that crunchy fruit is also feeding an invisible world inside you? New research ¹ has uncovered that when we bite into apples, carrots, and other fresh produce, we may be delivering microbes that seed our gut ecosystems, comprising the vast community of bacteria residing in our intestines.

Scientists from The Institute of Environmental Biotechnology ² in Austria have discovered a surprising new link between the fruits and vegetables we eat and the bacteria residing in our intestines. This new research has found that many types of gut bacteria actually originate from fresh produce, migrating to our digestive systems when we eat fruits, veggies and other plant foods.

By examining bacterial DNA, the researchers identified dozens of genera of bacteria that live both on produce and inside human intestines. These microbes make up a small but significant proportion of our gut ecosystems – on average close to 2% of an individual's unique gut bacteria come from fruits and vegetables.

This figure is higher among younger children and people who eat more vegetables. Although relatively few in number, these produce-derived bacteria provide health-promoting short-chain fatty acids (sidenote: Short chain fatty acids (SCFA) Short chain fatty acids (SCFA) are a source of energy (fuel) for an individual’s cells. They interact with the immune system and are involved in communication between the intestine and the brain. Silva YP, Bernardi A, Frozza RL. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol (Lausanne). 2020;11:25. ) , vitamin B12 and vitamin K. 

More Plant Diversity, More Gut Diversity

The study also showed links between produce consumption and gut health. Eating over 10 different types of fruits and vegetables weekly was associated with a greater diversity of gut bacteria compared to a less varied plant diet. People who ate more vegetables tended to have a greater variety of gut microbes.

This is one of the downsides of international travel: among other things, it encourages the spread of antibiotic resistance. As knowledge on the subject is still very patchy (studies on small cohorts, poorly characterized microorganisms, etc.) despite the threat posed by such resistance, a team has screened the microbiota of 267 Americans recruited in 3 clinics (Boston, New York and Salt Lake City) before and after a trip abroad.

Dysbiosis in travelers

The first finding of the study is that travel disrupts the intestinal microbiota, with a significant loss of microbial diversity in 61% of travelers, varying according to destination (from 42% of travelers to Central America to 76% of those who went to South America).

The abundance of Escherichia spp. and several other enterobacteria (Klebsiella, Enterobacter and Salmonella) increases with the acquisition of new strains, while the genus Alistipes virtually disappears. Travel to South Asia increases the risk of returning with an intestinal stowaway, while consumption of unfiltered tap water or prior vaccination against typhus seems to limit it.

When resistance travels

A third of the 267 travelers reported diarrhea and 18% of them were treated with antibiotics.

More significantly, on returning from their trip, 38% of the 267 travelers had acquired at least one of the 3 types of resistant bacteria targeted by this study: of these, 98% acquired extended-spectrum beta-lactamase-producing Enterobacteriaceae (sidenote: Extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae Enterobacteria that produce enzymes (extended-spectrum lactamases) with the ability to hydrolyze and cause resistance to various types of newer antibiotics. Klebsiella pneumoniae and Escherichia coli are the main ones. ESBL-producing Enterobacteriaceae, which make up the majority of multi-resistant bacteria, are responsible for potentially severe infections and prescriptions for broad-spectrum antibiotics. Sources :

Pitout JD, Laupland KB. Extended-spectrum beta-lactamase-producing Enterobacteriaceae: an emerging public-health concern. Lancet Infect Dis. 2008 Mar;8(3):159-66. doi: 10.1016/S1473-3099(08)70041-0. Et Vodovar D, Marcadé G, Raskine L et al. Entérobactéries productrices de bêta-lactamases à spectre élargi : épidémiologie, facteurs de risque et mesures de prévention [Enterobacteriaceae producing extended spectrum beta-lactamase: epidemiology, risk factors, and prevention]. La Revue de medecine interne, 34(11), 687–693. https://doi.org/10.1016/j.revmed.2012.10.365 ) (in 98% of cases, E. coli), 18% colistin-resistant Enterobacteriaceae, and 3% carbapenemase-producing Enterobacteriaceae.

And which risk factors encourage the acquisition of such resistance? Visits to friends and relatives, a trip to South Asia and eating raw vegetables. On the other hand, pre-departure intestinal diversity, the presence of a specific bacterial taxon, street food consumption and antibiotic use did not change the situation.

Limiting risks 

Among the types of resistance acquired during travel, fluoroquinolone resistance was particularly noteworthy: more than 1 in 2 travelers (56%) without resistance before the trip returned with at least one gene associated with resistance to an antibiotic in this class. In all, the group of 267 travelers returned to the United States with 72 new resistance genes, 15 of which are of public health concern!

These results call for warnings (especially for the riskiest destinations) and a reminder of good practices (cooked vegetables, hand-washing, etc.). Conversely, modulating intestinal microbiota before the trip (with probiotics, for example) would have no added value in this particular case.