The gut microbiota of infants born by Caesarean section (CS) differs from that of infants born vaginally since CS-born infants are not exposed to maternal microbes during delivery. Some studies report that CS may have short- and long-term consequences for infants’ health, including an increased risk of chronic immune diseases (asthma, allergies, etc.), although this claim remains controversial. A Finnish team has evaluated the efficacy and safety of fecal microbiota transplant (FMT) as a means of restoring the gut microbiota of babies born by CS.

Strict clinical protocol

Stool samples were collected from 17 mothers three weeks before the scheduled CS. A total of 7 women were selected following rigorous screening for pathogens in their stool. Within two hours of birth by CS, each baby received via bottle an FMT from its mother containing approximately 10⁶-10⁷ viable bacterial cells (1 mL of maternal stool diluted in 4 mL of breast milk). The gut microbiota and health status of each infant were evaluated at birth, for two days in the maternity ward, then every week for one month, and finally at three months. The composition of their gut microbiota was analyzed via 16S rRNA sequencing, then compared to that of 82 babies born vaginally or by CS without FMT.

Promising results

FMT did not give rise to any adverse effects or complications in the infants during the study period. The gut microbiota of FMT-treated CS infants and infants born vaginally differed in the first few days, then became similar after one week, but remained quite distinct from that of untreated CS-born infants. FMT appears to correct the bacterial signature of CS by bringing the abundance of Bacteroidales and Bifidobacteriales in line with that of vaginally born infants. In addition, the presence of potential pathogens was lower at one week and three months in FMT-treated CS infants compared to untreated CS-born infants. This first proof-of-concept study shows the safety and potential efficacy of FMT as a means of restoring the gut microbiota of infants born by CS. Larger-scale studies are required, but these results provide additional evidence of the importance of natural microbiota transfer from mother to child during childbirth.

Insomnia is a condition that interferes with onset, maintenance, and quality of sleep. It is generally linked to genetic, hormonal, immune or psychosocial predispositions, and it can have a serious impact on daytime functioning.

Gut microbiota in the dock

The gut microbiota may be to blame, specifically via the gut-brain axis, which enables communication between bacteria in the digestive tract and those in the brain. Various studies in animals have shown sleep disturbances to be frequently associated with changes in the composition and function of the gut microbiota (dysbiosis). Conversely, the restoration of normal gut flora improves the quality of sleep. These interactions are thought to involve cytokines (inflammatory molecules produced by the immune system in response to certain gut bacteria), which could explain the inflammation observed in insomniacs.

Bacterial “signatures” of insomnia

These data mainly result from work carried out on animals. Seeking confirmation in humans, researchers analyzed and compared the gut microbiota and cytokine production of 96 adults, including 20 suffering from acute insomnia, 38 from chronic insomnia and 38 normal sleepers, who served as controls. The first finding was that insomniac patients showed higher levels of inflammatory cytokines than normal sleepers, and these levels appeared to increase with the severity of the disease. Their microbiota also showed a depletion of certain bacteria known to produce short-chain fatty acids (compounds with anti-inflammatory and health benefits). The researchers also identified bacterial “signatures” that reflect the quality of sleep and the severity of insomnia. These signatures made it possible to distinguish acute and chronic insomniacs from normal sleepers.

Overcoming insomnia thanks to the microbiota?

This study confirms that there are alterations to the gut microbiota in cases of insomnia, the severity of which may be linked to the presence or absence of certain bacterial groups. Any resulting inflammation is thought to depend on the duration of the 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.   ) . The microbiota may therefore be used to develop diagnostic or therapeutic tools that target this sleep disorder.

The incidence of irritable bowel syndrome (IBS) increases following gastroenteritis episodes, suggesting that gut dysbiosis could play a role in its onset. However, research to date has focused on the microbiota of the intestinal lumen and has failed to find any clear link between the composition of this microbiota and IBS. Changing strategy, a team analyzed the bacteria present in the mucus lining of the colonic epithelium rather than that present in the lumen. This was done via sigmoid colon mucus samples taken from patients with IBS (with diarrhea, with constipation, with mixed bowel habits or unclassified) and controls.

Peptides indicating the presence of Brachyspira

Metaproteomic analyses on an explorative cohort (22 patients, 14 controls) identified microbial peptides derived from potentially pathogenic Brachyspira species in the mucus of 3/22 patients with IBS. Electron microscopy was used to confirm the presence of this bacterium, both at the colonocyte apical membrane and in the mucus. Quantitative real-time PCR (qPCR) combined with immunofluorescence analyses on the entire cohort (62 patients, 31 controls) detected Brachyspira colonization in 31% of IBS patients and in 42% of patients with diarrheal forms of the disease. No such colonization was observed in the controls.

Brachyspira colonizes colonocytes

The presence of Brachyspira specifically in the colonocyte apical membrane (as opposed to the mucus) was observed in 21% of the patients, and was associated with increased diarrhea and accelerated transit. These patients presented mild mucosal inflammation and mast cell activation. In addition, the abundance of mast cells was correlated with abdominal pain scores.

Antibiotics counterproductive?

In a final experiment, the researchers tested the effects of metronidazole in four patients. One year after treatment, three out of four saw a reduction in IBS severity. However, although Brachyspira was cleared from the epithelial surface, its presence in crypts and goblet cells may represent a novel mechanism of antiobiotic resistance. In conclusion, Brachyspira colonization in IBS (particularly at colonocyte level) appears to be associated with specific clinical, metabolic, and immune responses, thus providing a potential diagnostic tool for the different forms of IBS. In addition, antibiotic therapy in cases of IBS should be considered with caution due to the potential bacterial colonization that it could later cause.

Many new mothers experience the baby blues after giving birth. However, some mothers (and sometimes even their partners) may suffer from a much more severe and long-lasting form of depression known as postpartum depression. The precise causes of this disorder often remain unknown and only certain risk factors, such as genetic and/or environmental factors, have been identified. A recent study published in a scientific journal suggests the gut microbiota may also be involved.

Altered gut flora

Numerous studies have shown that changes to the gut microbiota may influence certain depressive disorders. In particular, there appears to be a link between anxiety in late pregnancy and gut microbiota imbalance. In this new study involving around sixty women, the composition of the gut microbiota of mothers suffering from postpartum depression showed alterations with respect to that of healthy women. In addition, the severity of depressive symptoms correlated with the presence of certain bacterial species.

Sex hormones at heart of problem

This gut imbalance (dysbiosis) may be caused by abnormal secretions of sex hormones. While female sex hormones (estrogen and progesterone) have already been implicated in the development of postpartum depression, this new study shows that they may play an important role in disrupting the gut microbiota of affected patients.

A new diagnostic and treatment avenue

These results may help scholars further explore the underlying causes of postpartum depression. While the scientific theories proposed in the study remain tentative, the microbiota characteristics identified may prove to be valuable diagnostic biomarkers or provide significant clues for future treatments.

A mind-boggling number of studies are published each month on the gut microbiota’s influence on brain function. Many of these studies focus on the role of gut microbiota imbalances in the onset or progression of Alzheimer’s disease (AD). The researchers in this study sought to identify the ways in which gut bacteria contribute to the disease, and more specifically to the accumulation of the dreaded amyloid deposits.

Uncovering the mechanisms at play in the gut-brain axis

To this end, they brought together around 90 individuals aged between 50 and 85, with or without AD, in order to study how the gut influences the brain. Analyses assessed the presence in their blood of: 1. molecules produced by bacteria from the gut microbiota; 2. inflammatory molecules; and 3. markers signaling the alteration of the gut barrier (allowing gut compounds to reach the bloodstream) and blood-brain barrier (allowing compounds to cross from the blood to the brain). The presence of amyloid deposits in the brain was also measured. The aim was to find associations between all these parameters in order to identify the mechanisms involved.

Bacterial and inflammatory compounds implicated

This search proved fruitful, with many strong associations found. For example, between amyloid deposits on the one hand and inflammation and presence in the blood of compounds from the gut microbiota on the other, or between these compounds and alterations to the permeability of the aforementioned barriers. An imbalance in the gut microbiota could therefore trigger an inflammatory mechanism capable of disrupting the body’s protective barriers, leading to the leakage of compounds into the brain and the potential formation of amyloid plaques. This finding opens the way to novel therapeutic approaches, such as the administration of a cocktail of beneficial bacteria (probiotics) to preserve the balance in the microbiota, particularly in at-risk individuals. The ingredients of this cocktail remain to be identified, however.

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The presence of a gut dysbiosis in patients suffering from Alzheimer’s disease has already been proven. So too has the microbiota’s involvement in the cerebral accumulation of amyloid beta proteins associated with the disease. This new study aimed to investigate the signaling pathways through which patients’ gut microbiota contributes to this amyloid pathology.

In search of correlations

The study involved 89 individuals aged between 50 and 85 with cognitive performance ranging from normal to cognitive impairment with memory loss (whether or not associated with the disease). Amyloid deposits were measured by PET-scan and quantified in the various areas of the brain, while blood levels of molecules produced by the gut microbiota (lipopolysaccharides–LPS–and short-chain fatty acids–acetate, propionate, valerate, butyrate), pro- and anti-inflammatory biomarkers (including interleukins–ILs) and biomarkers of endothelial dysfunction (cell adhesion molecules–CAMs) were also measured.

Bacterial mediators implicated

Regardless of the brain area, amyloid deposition was positively correlated with blood levels of LPS, acetate, valerate, certain pro-inflammatory cytokines (e.g. IL1b, IL6) and many CAMs (e.g. P-selectin, PECAM-1), but negatively correlated with butyrate and IL10 (anti-inflammatory) levels. Lastly, some biomarkers of endothelial dysfunction were positively correlated with acetate, valerate, IL1b and IL4 levels, but again negatively correlated with levels of butyrate and IL10. The authors interpreted these correlations as evidence of a direct and indirect association between blood parameters linked to gut dysbiosis and amyloid pathology.

Inflammation, barrier function and Alzheimer’s

Therefore, the reduction in butyrate levels associated with an increase in the levels of acetate, valerate and LPS may compromise the integrity of the gut barrier, cause and maintain low-level systemic inflammation, and alter the blood-brain barrier, ultimately allowing pro-inflammatory compounds facilitating the pathological cascade of Alzheimer’s disease to enter the central nervous system. While highlighting that no causal link could be established from their data, the authors emphasize that the strength of the associations found supports this pathophysiological hypothesis. Lastly, it may be possible to develop prevention strategies for Alzheimer’s based on enriching the microbiota with beneficial bacteria or metabolites, once the microbial signature associated with the disease has been clarified.

Type 1 diabetes mellitus (T1DM) is an autoimmune disease that leads to the destruction of pancreatic β-cells. Studies in mice suggest that interactions between the gut microbiota and the innate immune system are involved in the development of the disease, the progression of which may be slowed by fecal microbiota transplantation (FMT).

Autologous versus allogenic transplantation

In a randomized controlled trial, patients recently diagnosed with T1DM received three FMTs by nasoduodenal tube at 0, 2 and 4 months, either from their own feces (autologous FMT, n=10) or from the feces of healthy donors (allogenic FMT, n=10). In the year following the first FMT, the researchers evaluated residual β-cell function (via C-peptide release in response to a test meal), as well as metabolic, immune and microbiota changes induced by the two types of FMT.

Pancreatic function preserved

Contrary to the researchers’ expectations, β-cell function was preserved in the autologous group one year after the first FMT. β-cell function deteriorated in the allogenic group, however, although less than in T1DM patients not treated within the first year of diagnosis (sidenote: Overgaard AJ, Weir JM, Jayawardana K, et al. Plasma lipid species at type 1 diabetes onset predict residual beta-cell function after 6 months. Metabolomics 2018;14:158; Lachin JM, McGee PL, Greenbaum CJ, et al. Sample size requirements for studies of treatment effects on beta-cell function in newly diagnosed type 1 diabetes. PLoS One 2011;6:e26471 ) . According to the researchers, the benefits of FMT may be more pronounced and long-lasting where immunological compatibility between donor and host is high.

Desulfovibrio piger involved?

Changes in the microbiota were found to be associated with certain metabolic and immune changes. In the duodenum, the presence of Prevotella spp. was inversely correlated with residual β-cell function. In the colon, Desulfovibrio piger became significantly more abundant following autologous FMT only. Its abundance was associated with improved residual β-cell function and increased levels of plasma 1-arachidonoyl-GPC (A-GPC), a microbial metabolite associated with increased C-peptide production. In addition, the abundance of D. piger was negatively correlated with levels of certain T cells involved in autoimmunity. What was the significance according to the authors? D. piger may inhibit autoimmunity by suppressing these T cells via the production of A-GPC. From the multiple correlations found, the researchers have identified mechanistic leads that will need to be further investigated to clarify the effects of FMT on T1DM. They have also newly identified the therapeutic potential of certain bacterial species.

As you probably know, Maya the Bee lives surrounded by her half-sisters, since the queen spends her life producing eggs to populate the hive. However, despite their genetic similarity, she and her sisters recognize each other by smell! What’s more, this study suggests that a bee’s scent–a signal of hive membership–is directly linked to the gut microbiota shared with its nestmates

Recognizing their own by smell

The honey bee’s body is covered with scent molecules. This allows the guards at the entrance to the hive to recognize hive members and stop intruders trying to sneak in and steal food. A research team has recently shown that the olfactory cues are based on shared characteristics of the gut microbiota (bacteria, fungi and viruses colonizing the digestive system), rather than genetic similarity. Bees from the same colony share several types of identical bacteria in the gut, giving them their common scent. Conversely, bees from a different colony, whose microbiota is home to distinct bacteria, emit a different scent.

Mechanisms involved

How to explain this influence of the microbiota? A number of theories have been put forward. According to one of them, the colony-specific scent is derived from the smell of the gut microbiota itself. However, this hypothesis seems unlikely as it goes against previous studies suggesting the involvement of molecules secreted by cells located under bees’ “skin”, to which the gut bacteria have no access. A second, more likely, theory suggests that the microbiota of honey bees quantitatively and qualitatively influences the production of scent molecules, for example, by providing their ingredients (or failing to do so). This scent recognition system is very useful to bees, but also has advantages for their gut bacteria: by rejecting bees with a distinct digestive flora, the hive also limits the entry of different bacteria, offering the organisms in the microbiota a quiet life, without competition.

Introversion, social anxiety... alcoholics display alterations in social behavior that may facilitate relapse. Alcohol consumption can lead to a dysbiosis of the gut microbiota, which in turn is known to be a modulator of social behavior in rodents. Hence the theory that the gut microbiota may be involved in the sociability problems associated with alcoholism. To test this hypothesis, a team of researchers transplanted (FMT ) into mice the microbiota of alcoholic patients suffering from a dysbiosis (reduced bacterial count, reduced content of Faecalibacterium prausnitzii and increased content of Lachnospiraceae), increased gut permeability and psychological disorders (anxiety, alcoholic impulses, impaired sociability, etc.).

Microbiota was enough to modify behavior

The results? The mice which received the transplant (FMT) showed a reduced interest in social interactions and more depressive-like behavior, as well as higher corticosterone levels, reflecting higher levels of stress. Disturbances of myelination and neurotransmission, as well as inflammation, were observed in the frontal cortex and striatum.

β-hydroxybutyrate, a metabolic mediator?

β-hydroxybutyrate (BHB), a ketone body produced by the liver that serves as an energy source for neurons may be involved in the behavioral and brain disorders observed. Reduced in the FMT mice, it is one of the metabolites distinguishing them from controls. Studies in other animal models and in humans supports the involvement of BHB. In mice, an increase in plasma BHB levels under the ketogenic diet improved social skills and myelination and reduced brain inflammation. In alcoholics, low plasma BHB levels were associated with higher levels of social anxiety, depression and alcohol craving, and lower white matter integrity (one of the determinants of which is myelination).

Is microbial ethanol involved?

But how would the microbiota influence plasma BHB levels? The microbiota of alcoholic patients produces ethanol, even with protracted alcohol withdrawal, an observation confirmed in FMT mice. The authors believe this alcohol may inhibit the Hmgcs2 enzyme and PPARα transcription factor, which are involved in the synthesis of BHB. Indeed, the expression of these two molecules is lower in FMT mice. Restoring the microbiota or ketone body metabolism is one clinical avenue that may result from this work: by favorably modulating the gut-brain axis, this may help limit relapse.

Atopic dermatitis (or atopic eczema) is a chronic inflammatory skin disease that starts in early childhood as eczema patches appearing during flare-ups. The disease disappears in most cases during adolescence. Changes in the skin microbiome have been associated with atopic dermatitis and its severity, with an overabundance of Staphylococcus aureus and S. epidermidis in lesions, and a reduced abundance of streptococci during inflammatory flare-ups. Furthermore, the nasal microbiota is suspected of acting as a bacterial reservoir and of maintaining self-contamination between the skin and the nose, although few data support this theory.

Nose and skin: two connected microbiomes?

A team of researchers analyzed samples taken from the nose and lesioned skin of children suffering from atopic dermatitis. While the skin lesions were almost exclusively colonized by staphylococci, these species were far from the majority in the nasal microbiome, which is more diverse and dominated by other bacteria (Moraxella, Corynebacterium, Dolosigranulum). However, these distinct compositions do not prevent the nasal and skin microbiomes from interacting, as indicated by the statistical association between the bacterial species in the nasal passages and those present on the skin. However, the mechanisms involved are not fully understood.

Two microbiomes associated with severity

In addition, the composition of the nasal and skin microbiomes, and particularly that of the skin microbiome, was found to be linked to the severity of the disease. This link is mainly due to the presence of staphylococci in both microbiomes, but other species also play a role, such as Moraxella in the nose. According to the authors, these results suggest that the skin and nasal microbiomes play a role in exacerbating the inflammation caused by atopic dermatitis. The authors call for further research in order to identify more precisely the species and various microbiomes involved in the disease.