Kissing your partner, breastfeeding and hugging your baby, sharing a pizza with roommates, or simply being together in the same space at a given time:   living together means much more than simply sharing a roof. It also means sharing a microbiota, with the extent of transmission depending on factors such as age, the type of relationship, and the amount of time spent together. A new study has shed some light on the importance of interpersonal relations for our gut and oral microbiota.

Gut microbiota under maternal influence

Kinship has the greatest influence. At birth, a baby shares 65% of its gut microbiota strains with its mother, a sort of “starter kit” provided at delivery. This rate progressively decreases as intimacy wanes, falling to :

• 50% at 1 week;
• 47% at 1 year;
• 27% between 1 and 3 years;
• 19% up to 18 years;
• and 14% up to 30 years.

However, a non-negligible remnant of the maternal imprint defies both space and time, with offspring at 50-85 years of age still sharing 16% of gut strains with their mother, even if they no longer live under the same roof.

Unexpected effect on the oral microbiota of living together

The dynamics of the oral microbiota are very different. Instead of decreasing, the sharing rates increase with age, especially after 3 years, a pivotal age from which the number of oral microbiota species multiplies. However, parents may be surprised to hear that their offspring will share more oral bacteria with roommates and, especially, partners (38%) than they ever shared with their mother (30%) or father (24%).

Spreading bacteria with your neighbors

More surprisingly, the study reveals that we exchange bacteria beyond the walls of our home. Adults living in the same town but under different roofs share 8% of their gut microbiota strains and 3% of their oral microbiota strains (compared with 0% for residents of separate towns), most likely due to physical interactions and a shared environment.

Effect of Western lifestyle

On the other hand, the researchers noted that lifestyle (Western vs. non-Western) has a much lower-than-expected impact on microbe transmission between individuals. Western microbiota is certainly characterized by low microbial richness. However, strain sharing rates are similar across countries, suggesting that the greater richness in non-Westerners’ gut and oral flora is due to interactions with their environment and diets that promote diversity rather than to increased transmission between individuals.

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Will it soon be possible to predict gestational diabetes (GDM) in the first trimester of pregnancy? So suggests a recent study published in the journal Gut.  

Israeli researchers recruited 394 women aged between 18 and 40 who were less than 3 months pregnant. The researchers collected stool samples to analyze their microbiota and blood samples to measure parameters such as blood glucose and serum cytokines. The researchers also recorded the participants’ medical history and dietary habits.

The participants were then followed for 27 to 30 weeks. In the second trimester, 44 of them (11%) developed GDM.
 

Clear differences in women with gestational diabetes

The results of the blood analyses showed that, as early as the first trimester, women who developed GDM had glucose intolerance and high levels of cytokines, particularly of interleukin-6 (IL-6), unlike the women without GDM. Several studies have shown that, by promoting inflammation, IL-6 is involved in various forms of diabetes, including GDM.

The analysis of the gut microbiota showed that as early as the first trimester women with GDM also presented:

• A decrease in short-chain fatty acids (SCFAs), especially isovalerate and isoburate, which are known to improve insulin sensitivity and lower inflammatory responses;
• A lower abundance of Prevotella, whose presence is associated with improved glucose metabolism;
• An enrichment of certain metabolic pathways, such as mevalonate, which is associated with increased IL-6 levels.

Symptoms reproduced in mice through microbiota transplant

To find out whether these characteristics play a role in the pathogenesis of GDM, the researchers then transplanted the fecal microbiota (FMT) of the women in the study into germ-free mice (lacking microbiota). 

They observed the same symptoms in the FMT mice as in the women with GDM: glucose intolerance and higher levels of IL-6. This suggests that the microbiota may be involved in the pathogenesis of GDM. 

The results were the same for FMTs from pregnant women in two other cohorts from Finland and the US, suggesting the “universal” nature of the microbiota changes associated with GDM.

Towards new detection tools?

The researchers then used a prediction model to see which first trimester data (microbiome composition, cytokine profile, medical history, or dietary characteristics) most accurately predicted GDM. The results indicated that the model incorporating the medical record was the most accurate (odds ratio – OR – = 3.2), followed by the model based on the fecal microbiota. Using both models together, the OR increased to 4.
Although further studies are needed to determine whether dysbiosis is caused by diabetes or vice versa, these results suggest it may be possible to manage GDM from an earlier stage and, more importantly, to mitigate the adverse effects of the disorder on the health of mother and child.

It is a long-lasting misconception that gestational diabète mellitus (GDM) is triggered in the second or third trimester of pregnancy. A recent study published in the journal Gut says otherwise. Changes in the gut microbiota linked to this sugar metabolism disorder may clearly appear as early as the first trimester, potentially opening the door to new predictive tools.

Nearly 400 pregnant women followed over several weeks

Researchers from Bar-Ilan University in Safed, Israel, recruited 394 women aged between 18 and 40 who were less than 3 months pregnant. The researchers collected stool samples to analyze their microbiota and blood samples to measure inflammation levels and various other parameters. The participants were then followed over several weeks. During this follow-up, 44 women developed GDM (11%).

Diabetes driven by microbiota-induced inflammation

By comparing their blood results to those of unaffected women, the researchers found that, as early as the first trimester, women with GDM had glucose regulation problems and higher levels of inflammatory messengers, particularly interleukin-6 (IL-6). Several studies have shown that, by promoting inflammation, IL-6 is involved in various forms of diabetes, including GDM.

In addition, a microbiota analysis showed alterations (dysbiose (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 some bacterial communities in women with GDM. There were also fewer short-chain fatty acids (SCFAs (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. ) ) compounds produced by bacteria that lower inflammation and improve sensitivity to insulin (and thus blood sugar management).

By transferring the microbiota of women with GDM into mice with no microbiota, the researchers reproduced the symptoms of GDM, including the inflammation associated with increased IL-6, demonstrating that dysbiosis is indeed at play in the development of GDM.

A step towards more efficient predictive tools that detect GDM earlier?

Lastly, the researchers used a prediction model to find out which parameters were the most relevant for predicting GDM accurately and early. While data from the patient’s medical record (weight, height, history, blood sugar levels, etc.) gave the most accurate predictions, data from the microbiota strongly improved predictive accuracy.

Despite certain limitations, this study is a further step towards understanding GDM. It also opens the door to high-precision detection methods allowing better management of GDM and a reduction in the associated risks.

Excellent news given the increasing prevalence of the disease worldwide due to the surge in cases of excess weight and obesity.

An altered gut microbiota composition has already been reported in metabolic, cardiovascular, oncological, neurological and psychiatric disorders. According to the results of a study published in early 2023 by a South Korean team, we can now add migraine to this long list. The researchers studied the stools of 42 individuals with episodic migraine, 45 individuals with chronic migraine (sidenote: Chronic form of migraine Headache for ≥ 15 days per month with ≥ 8 migraine features (increased sensitivity to light, sound or smells, nausea, vomiting…) for > 3 months.  Weatherall MW. The diagnosis and treatment of chronic migraine. Ther Adv Chronic Dis. 2015 May;6(3):115-23. ) and 43 healthy controls, all aged between 19 and 65 years.  The researchers excluded patients undergoing medical or psychiatric treatment other than for anxiety, depression, or fibromyalgia, those who had significantly changed their dietary habits in the previous six months, and those who had taken probiotics or antibiotics in the previous year.

However, all patients took migraine treatment in the case of an episode and 60% were taking disease-modifying treatments (anti-epileptics, beta-blockers, etc.), which may represent a bias (impact on the microbiota) and was taken into account in the analysis of the results.

Microbiota varies according to the study group

No significant differences were observed between the three groups in terms of alpha (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 ) and beta (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 ) diversity in their gut microbiota. However, the composition of the gut microbiota differed significantly:

• the class Tissierellia and the order Tissierellales  were overrepresented in the 87 individuals with migraine compared to the 43 controls. At the genus level, Roseburia, Eubacterium_g4, Agathobacter, PAC000195_g, and Catenibacterium were more abundant in the migraine groups.
• the class Bacilli and the orders Selenomonadales and Lactobacillales were less abundant in the chronic migraine group compared to the episodic migraine group, as were the classes Selenomonadaceae and Prevotellaceae. At the genus level, the bacterium PAC001212_g predominated in the chronic migraine group, whereas Prevotella, Holdemanella, Olsenella, Adlercreutzia, and Coprococcus characterized the episodic migraine group.

^{Sources (sidenote: Burch RC, Buse DC, Lipton RB. Migraine: Epidemiology, Burden, and Comorbidity. Neurol Clin. 2019 Nov;37(4):631-649. )}

Bacteria linked to headache frequency or intensity

Additional analyses show a link between certain bacterial genera and the clinical characteristics of migraine: a higher composition of PAC000195_g was significantly associated with lower headache frequency; whereas Agathobacter revealed a significant negative association with severe headache intensity.
While these results provide evidence of gut dysbiosis in individuals with migraine, only longitudinal studies will allow us to better understand the relationship between the gut microbiota and migraine (causes and consequences) and, ultimately, the potential to find prophylactic treatments against migraines via the gut microbiota.

Those who suffer from migraines are known to be more prone to gastrointestinal disorders such as diarrhea, constipation, and gastroesophageal reflux. A South Korean study published at the beginning of 2023 shows that they also have an altered gut microbiota.

Altered gut flora in individuals with migraine

By analyzing the bacteria present in the stools of 87 individuals with migraine (42 with episodic migraine and 45 with chronic migraine (sidenote: Chronic form of migraine Headache for ≥ 15 days per month with ≥ 8 migraine features (increased sensitivity to light, sound or smells, nausea, vomiting…) for > 3 months.  Weatherall MW. The diagnosis and treatment of chronic migraine. Ther Adv Chronic Dis. 2015 May;6(3):115-23. ) ) and 43 healthy controls, the researchers observed differences in their gut microbiota composition: in those suffering from migraine, bacteria of the genera Roseburia, Eubacterium, Agathobacter, PAC000195  (a previously undescribed bacterium), and Catenibacterium were more abundant than in people not affected by the disorder. There were also differences in certain gut bacteria according to the type of migraine (episodic or chronic): PAC001212 were characteristic of the chronic migraine group, while Prevotella, Holdemanella, Olsenella, Adlercreutzia, and Coprococcus were associated with episodic migraines.

^{Sources (sidenote: Burch RC, Buse DC, Lipton RB. Migraine: Epidemiology, Burden, and Comorbidity. Neurol Clin. 2019 Nov;37(4):631-649. )}

Bacteria as an indicator of headache severity

Furthermore, the presence of certain bacteria may predict key parameters of migraines. A higher content of PAC000195 was significantly associated with lower headache frequency, whereas Agathobacter revealed a significant negative association with severe headache intensity.

Microbiota and migraine: chicken or egg?

However, this does not mean that these bacteria protect against migraines and prevent their recurrence, or that others exacerbate migraines.  The results of this study merely show that individuals with migraine suffer from a gut dysbiosis. We cannot say for sure whether this imbalance is the cause or consequence of the migraine. The only way to find out is by performing longitudinal studies that follow the patients over time and look for variations in the microbiota that precede or follow migraine attacks, thus showing whether one factor triggers the other. This may in turn lead to the development of treatments for this disease.

Allergies and microbiota: what are the links?

The microbiota involved

Protective factors

Do disturbances of the gut-brain axis contribute to alcoholism?

Gut dysbiosis and an increase in inflammatory markers have already been identified in chronic alcoholics, particularly in cases of severe AUD and compulsive alcohol drinking. They appear to lead to neuroinflammation, which in turn results in cognitive and behavioral disorders, particularly social disorders. 
Deficits in social cognition have been reported in young binge drinkers. These dysbiosis and disturbances of the gut-brain axis may thus be involved in the transition to alcohol addiction.

An Irish team conducted a study on 71 young people aged 18 to 25 (37 women, 34 men) who were not dependent on alcohol in order to identify early signs of AUD among binge drinkers. The researchers explored the links between gut dysbiosis, inflammation, alcohol cravings, sociability deficits and impulsivity, a cognitive trait known to accelerate the transition to alcohol addiction. To do so, they subjected the participants to a neuropsychological evaluation, measured inflammatory markers in biological samples (blood, saliva, etc.) and, lastly, carried out metagenomic sequencing on fecal samples. During the three months of follow-up, the participants recorded their alcohol consumption and alcohol cravings.

Dysbiosis associated with binge drinking and cognitive impairment

The researchers observed that binge drinking was accompanied by specific taxonomic and functional imbalances in the gut microbiota, which in turn were associated with emotional regulation disorders. Statistical analyses showed that altered emotion recognition was linked to a decrease in Clostridium, Flavonifractor plautii, and Eggerthella lenta species, and an increase in Coprococcus species. Impulsivity was associated with a decrease in Collinsella and an increase in Roseburia and Parabacteroides. Compulsive alcohol drinking was correlated with a reduction in Ruthenibacterium lactiformans and an increased release of interleukins, a sign of immune overstimulation. Lastly, engaging more frequently in binge drinking was associated with decreased production of short-chain fatty acid isovalerate and increased impulsiveness.

Modulating the gut microbiota in the vulnerable period of adolescence

This study highlights the gut microbiota’s role in regulating social cognition and impulsiveness, and demonstrates that binge drinking is associated with alterations in the gut microbiota that foreshadow the onset of alcohol dependence. This may pave the way for new dietary or pre-/probiotic interventions to improve alcohol-related dysbiosis during the critical developmental period of adolescence.

Binge drinking leads to acute intoxication. Young people aged between 15 and 25 are most likely to engage in binge drinking. The practice has harmful effects on health during adolescence, since the body is still under development during this period. When practiced regularly, binge drinking alters the structure and functioning of the brain and increases the risk of developing alcohol use disorder, i.e. alcoholism, later in life.

Chronic alcoholics display gut microbiota imbalances (dysbiosis), and the stronger their cravings for alcohol, the more severe the imbalances. These imbalances are thought to cause inflammation of the brain, which in turn affects emotional regulation and​​​​​​​ social cognition (sidenote: Social cognition Ability to understand and manage social interactions. Beaudoin C, Beauchamp MH. Social cognition. Handb Clin Neurol. 2020;173:255-264. ) . Moreover, studies now suggest that dysbiosis and disturbances of the gut-brain axis may also be involved in the development of alcohol dependence.

Identifying signs of vulnerability to alcoholism in young binge drinkers

Irish researchers have sought to explore the links between dysbiosis, inflammation, compulsive alcohol drinking, and emotional control disorders in young binge drinkers. To do this, they brought together 71 men and women aged 18 to 25, who were not addicted to alcohol. They subjected the participants to a neuropsychological evaluation, analyzed samples of their biological fluids for markers of inflammation, and collected stool samples to analyze their gut microbiota. The participants recorded their alcohol consumption and alcohol cravings over a three month period.

^{Sources. (sidenote: Interministerial mission against drugs and addictive behaviors: Binge drinking. https://www.drogues.gouv.fr/le-binge-drinking )}

Cognitive problems and a transition to alcohol addiction

At the end of the study, the researchers found that young binge drinkers presented a dysbiosis specifically linked to cognitive disorders. Impaired emotion recognition (sidenote: Emotion recognition Ability to identify and describe one’s own emotional states and those of others. Cabé N, Laniepce A, Boudehent C et al : Repérage des troubles cognitifs liés à l’alcool, La Revue du Praticien, 20/10/2019, 69(8);904-8 ) and impulsiveness were each associated with changes in the presence of specific bacterial groups. Irresistible cravings for alcohol were linked to a reduction in an additional bacterial species and an increase in markers of inflammation. As the researchers expected, a greater number of binge drinking episodes increased impulsiveness, which is known to accelerate the transition to alcohol addiction.

Skin color, age, sex... Discrimination takes many forms but always has the same intent: to reject and exclude a person or a group of people. According to a study of different American populations, discrimination may affect not only the digestive system (specifically the gut microbiota), but also the brain system and the communication between the two (known as the gut-brain axis). More surprisingly, the effects and mechanisms at play could depend on the person’s ethnicity.

Effects of discrimination: causing havoc with the gut microbiota in African-Americans

Among African-Americans, high discrimination, usually based on skin color, can even affect the bacteria found in the gut microbiota, creating a condition known as dysbiosis.

For example, the researchers found increased levels of bacteria, especially a proinflammatory species called Prevotella copri, in African-Americans who had been subjected to high levels of discrimination. Brain images (using MRI, or Magnetic Resonance Imaging) reveal stimulation of areas involved in the regulation of negative emotions. In terms of mental health, although high discrimination led to increased levels of anxiety and stress (as with other groups), there was no observable association between discrimination and mental health (unlike for other communities). According to the authors, discrimination does trigger strong inflammation among African-Americans, but this group is more resilient and less prone to depression.

Different mechanisms for other communities

Comparable assessments of the gut microbiota, blood markers, brain activity, and mental state revealed very different responses in the other groups.

• Among Hispanics, discrimination was also associated with inflammation, but it was overcome by better coping strategies and cognitive control.
• Asians appeared to demonstrate very different mechanisms: increased discrimination went hand in hand with increased metabolites related to cholesterol and brain activity, suggesting that they dealt with stress by eating foods high in fat.
• Finally, the discrimination experienced by Caucasians was primarily based on age and sex. It was associated with anxiety but not inflammation. Their guts contained a lower concentration of P. copri compared to the Hispanic and African-American communities. The MRI results for this group also showed brain changes that could indicate coping difficulties.

Despite widespread consensus that discrimination is a risk factor for mental and physical disorders, the exact mechanisms remain unclear. The hypothalamic-pituitary-adrenal axis has often been cited. However, some experts have now turned their attention to the gut microbiota in light of its extreme sensitivity to stressors, its role in inflammation and long-term health, and recent results with the gut-brain axis. A study published in 2022 investigated the effects of discrimination on dysregulation of the gut-brain axis.

Brain rewiring

Of the 154 participants in this study, 80 had experienced high levels of discrimination and 74 had experienced low levels of discrimination based on the color of their skin (African-American, Hispanic and Asian individuals), sex or age (Caucasians). High levels of discrimination went hand in hand with higher levels of anxiety, depression, and visceral sensitivity. However, the associations varied by ethnicity, with African-American individuals showing no association between discrimination and mental health, for example.

Physiologically, MRI results found that discrimination was associated with variable changes in stress brain connectivity pathways, depending on ethnicity: for example, in Asian individuals, discrimination was associated with higher stimulation of areas of the brain engaged in interoceptive, autonomic, sensory, motor, and reward processing, whereas Caucasian participants displayed a “chaotic” connectivity in numerous brain networks, etc.

Dysbiosis of the gut microbiota

As well as these changes in the brain, discrimination also appears to be associated with gut dysbiosis and higher levels of the proinflammatory bacterium Prevotella copri among African-American and Hispanic individuals compared to Caucasian subjects. Bacterial metabolites were also affected, again with group-based variations: lower concentrations of a by-product of carnitine synthesis (an anti-inflammatory) among African-Americans; increase in metabolites involved in lipid metabolism among Asians, etc.

Discrimination with ethnicity-mediated consequences ?

The authors believe that discrimination affects the gut-brain axis, with consequences that vary between communities.

• Among African-Americans, there is a stronger association with inflammatory biomarkers, but this group appears less prone to anxiety and reports the highest resilience scores.
• Among Hispanics, discrimination is also associated with inflammation, but this group has better coping strategies.
• The results for Asians suggest they deal with stress by a diet high in fat.
• For Caucasians, the observed brain changes could indicate coping difficulties.