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Dad’s gut microbes matter for pregnancy health and baby’s growth

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THE PAPER IN BRIEF

• Gut bacteria can affect biological processes at body sites far from the gut.

• The extent to which gut bacteria can affect reproductive tissues is not fully understood.

• Argaw-Denboba et al.1 report that altering the community of gut bacteria in male mice had negative consequences for the health and lifespan of offspring.

• Abnormalities in sperm RNA and the placenta were some of the changes associated with changes to male gut microbes.

• More work will be needed to uncover all the mechanisms underlying this phenomenon.

LIISA VEERUS & MARTIN J. BLASER: The power of paternal bacteria

The microbial communities living in and on animal hosts have become a notable focus of scientific research in recent decades. Studies have explored the many interactions that these microbiomes have with their hosts, and the consequent implications for health and disease. Argaw-Denboba and colleagues now present work that contributes to the emerging field of cross-generational microbiome effects. They investigated how the gut microbiome of male mice might affect the health of the animals’ offspring through changes in the paternal germline tissue, which contains the cells that form sperm. The authors’ observations pointing to a gut–germline axis could, if confirmed, shift the focus of microbiome research from the current mother–newborn model2 towards a new mother–father–newborn interactive system.

After changing the community of gut microbes in prospective fathers by administering either gut-specific (primarily non-absorbable) antibiotics or laxatives, the authors showed that the sperm from a father with a perturbed gut microbiome triggered changes in the placenta (which forms from cells of the embryo) that developed in its mating partner. Some of the resulting offspring had a lower birth weight and a higher chance of premature death (Fig. 1) than did offspring of fathers with a normal microbiome.

Figure 1

Figure 1 | The effect of male gut microbes on offspring health. Argaw-Denboba et al.1 report that using antibiotics to alter the community of gut microbes in male mice affected the production of healthy sperm in a way that had negative consequences for the development of embryonic cells into the placenta and for offspring weight and lifespan. The molecular pathways underlying this phenomenon are not yet fully understood. The effect was reversed after recovery from antibiotic treatment.

By using a variety of methods, such as microbiome transplantation, in vitro fertilization and analysis of gene expression, Argaw-Denboba et al. go beyond correlation to pinpoint that the disadvantageous effect in the offspring is transferred through sperm cells, not through the paternal microbiome. And they demonstrate that the effect is not inherited genetically, but through epigenetic modifications (alterations that do not change the DNA sequence) in the male reproductive system, with differences in sperm RNA reported. The authors also show that the paternal microbiome was restored naturally within eight weeks of the perturbation, and that this restoration was associated with a return to producing healthy offspring, indicating that the microbiome alteration effect was short-lived.

One limitation of the study is that it does not define the molecular pathway through which the perturbed gut microbiome affects the male germline. Doing so could be a goal of future research. The authors note that the disadvantageous aspects of offspring development, including severe growth restriction, did not arise in all offspring, suggesting that further investigation will be required to understand the proposed gut–germline axis and its effect on offspring health.

Whether these findings in mice are also relevant to humans remains to be determined. Another interesting question is how long the gut microbiome takes to recover in people who receive a course of antibiotics. The authors’ finding that the negative effect is reversible might prove useful in providing advice on the optimal timing for fertilization, to avoid costs to the offspring.

Argaw-Denboba and colleagues’ carefully planned research demonstrates how little we still know about antibiotics’ potential effects and underlying mechanisms in relation to crucial concerns such as healthy fertilization and offspring. Exploring the modulation of the gut microbiome and the consequent effects across organ systems is a scientific frontier. Although the health implications of antibiotic use in mothers and newborns have garnered interest in previous publications3,4, the role of fathers has been mostly ignored. This study shows that the preconception microbiome has a role, and that fathers are not just gene donors, but can also, through their microbiomes, affect their offspring’s health5.

YOEL SADOVSKY & ELDIN JAŠAREVIĆ: A father’s microbes and pregnancy outcomes

In mammalian species that form placentas, embryonic development and subsequent fetal growth depend on the genetic contributions and related signals carried in the egg and the sperm, with roles for the placenta, the maternal host tissues and the external environment. These influences are mediated by the exchange of gases, nutrients and metabolic waste, and are modulated by hormones. They are also affected by exposure to microbial or viral disease-causing agents and to inflammation, toxic compounds and social and behavioural stressors. The integration of these signals determines the outcome of pregnancy, and adverse influences can compromise fetal and maternal health and lifespan.

A key challenge in studying pregnancy relates to the dynamic and complex signals arising from factors that the parent encounters during their lifetime (described as lifetime exposures), and to how these signals affect fetal and placental development. A mother might generate or modulate health-related signals in many ways during pregnancy. By contrast, the father’s influences are limited mostly to sperm-dependent genetic (DNA) contributions, and to effects resulting from epigenetic modifications of DNA and its associated proteins, which are commonly induced by stress and dietary changes6,7. Paternal effects on offspring health, such as those mediated by stress, exposure to inhaled or ingested chemicals, or male help in providing maternal nutrition, are thought to be indirect when compared with the more direct maternal effects on the offspring.

A growing body of work demonstrates that gut bacteria and the metabolite molecules that they produce are key intermediaries between maternal lifetime exposures, pregnancy outcomes and lasting outcomes for offspring8–10. In their related findings, Argaw-Denboba and colleagues add an unexpected dimension to parental gut microbiome influences on gestational biology — namely, the effect of antibiotic-mediated disruption of the paternal microbiota on a male germline. Using mice, the authors established a strong association between a perturbed paternal gut microbiome and sex-independent restriction of fetal growth; the resultant low birth weight lingered into early adulthood and was associated with reduced survival times compared with the offspring of males who had unperturbed gut microbes.

Crucially, the effect was reversed when the paternal gut microbiome was restored to normal by ceasing antibiotic exposure, and was recapitulated through in vitro fertilization using sperm from males harbouring the perturbed gut microbiome. Furthermore, the altered paternal microbiome was associated with changes in male reproductive tissue (smaller testes and seminiferous tubules with a swollen (vacuolated) appearance and thinner than normal layers of epithelial cells). The authors observed intact genomic parental-specific expression of genes (imprints) but altered transcriptome, metabolome and methylome profiles (relating, respectively, to gene expression, production of metabolite molecules and the attachment of methyl groups to DNA); these profiles were of unknown relevance to the observed outcome.

Do any of these changes causally explain the prenatal and postnatal effects on the offspring? Examining samples of fetal and placental tissue, Argaw-Denboba et al. listed a series of changes in the fetal gene-expression profiles, highlighting differentially expressed genes related to lipid and metabolic processes. These changes were associated mainly with the fetal brain and brown adipose tissue. Placental analysis at embryonic days 13.5 and 18.5 revealed a smaller labyrinth (the mouse placental region that governs gas and nutrient exchange between the mother and the fetus) and impaired formation of blood vessels.

Gene-expression analysis highlighted altered expression of genes related to a metabolic process called glycolysis, to the metabolism of molecules called prolactin and steroids and to several regulators of placental development (such as the genes Hand1 and Syna). Intriguingly, some of the transcriptional changes can cause placental dysfunction. Certainly, further characterization will be crucial to determine whether effects similar to those observed in the placenta-associated condition pre-eclampsia (which involves maternal hypertension and target-organ injury and can lead to fetal or maternal illness or death) are an underlying cause of disease in this context.

These exciting observations establish a link between the paternal gut microbiota, sperm RNA content and pregnancy outcome. Although the mechanisms linking altered sperm biology with changes in the offspring and placenta and with altered gene expression remain to be unravelled, this line of investigation highlights antibiotic-mediated disruption of the paternal gut microbiota as a previously unknown mode of a sperm-mediated effect on fetal development and offspring health. Furthermore, if validated in humans, the work might indicate a potentially modifiable preconceptional contribution by the father’s microbiome to pregnancy health, which would be a pioneering concept in the biology of human pregnancy.

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Gut bacteria can break down artery-clogging cholesterol

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Illustration of a lipid nanoparticle mRNA vaccine, a type of vaccine used against COVID-19 and influenza.

A new drug consists of pieces of mRNA encased in a fatty envelope (artist’s impression).Credit: Kateryna Kon/SPL

A therapy that extends mRNA technology beyond vaccines has shown early success in treating a rare genetic disease, propionic acidaemia, that prevents people from processing certain nutrients. The treatment — made by US pharma company Moderna, and known as mRNA-3927 — gives those treated a working copy of the instructions needed to make an enzyme that is missing in people with the disease. In a small clinical trial, half of the participants receiving the therapy saw their risk of life-threatening episodes decrease by 70–80%. But the drug also produced side effects and required frequent infusions.

Nature | 5 min read

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Nature | 3 min read

A fertility treatment that has been used for 45 years is back in Alabama after being halted in February by the state’s Supreme Court. The court ruled that embryos created using in vitro fertilization (IVF) have the same rights as children, but a new state law in Alabama that protects clinics from legal fallout has allowed IVF treatments to resume. US clinicians and scientists who are working with human embryos are not totally reassured and fear that they will face an increasing number of legal and constitutional challenges. “From a researcher’s perspective, there’s reason to be worried,” says Hank Greely, director of the Center for Law and the Biosciences at Stanford University.

Nature | 5 min read

Researchers have identified gut bacteria that can transform artery-clogging cholesterol into a more harmless form. In previous work, the authors showed that a bacterial enzyme called ismA can metabolize cholesterol into coprostanol, a lipid that is excreted instead of absorbed by the body. They have now identified gut bacteria, including several Oscillibacter species, that correlate with lower cholesterol levels in people. These species could also metabolize cholesterol in lab experiments. Whether these bacteria can directly influence blood cholesterol in people needs to be confirmed, but if they could be delivered to the right place in the gut, it might lead to new treatments.

Nature | 4 min read

Reference: Cell paper

Infographic of the week

‘CROWN’ JEWELS. Graphic labelling features of the Sun's corona.

Source: Nature adaptation from image provided by Nicolas Lefaudeux

Features & opinion

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LONELINESS AND HEALTH. Graphic shows lonely adults are more likely to be diagnosed with a range of physical health issues.

Source: The Cigna Group

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Nature | 5 min read

“Astrophysics is an exercise in incredible experiments not runnable on Earth,” says theoretical physicist Avery Broderick. “And black holes are an ideal laboratory.” What makes black holes appealing to physicists is their extreme simplicity: an extraordinary amount of mass in a ridiculously small space. Black holes also challenge physicists’ ideas about general relativity and quantum mechanics. Astronomers can observe the gravitational waves emitted by colliding black holes, and maybe understand how they deviate from Einstein’s theories.

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Quote of the day

The loss of pristine tropical forests slowed last year, but ten football pitches’ worth of forest were still lost every minute in 2023, found an analysis by environmental scientist Mikaela Weisse and her colleagues at the environmental think tank World Resources Institute. (Nature | 3 min read)

Reference: Global Forest Watch map

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Gut bacteria break down cholesterol — hinting at probiotic treatments

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Scientists have pinpointed human gut bacteria that have a useful tool: an enzyme that can convert artery-clogging cholesterol into a more harmless form that is not absorbed by the body. The finding points towards possible treatments for high cholesterol levels.

Although the newly described bacterial species can metabolize cholesterol in the laboratory, whether they can cause changes in their hosts’ blood cholesterol levels has yet to be confirmed in animal models or clinical trials.

“It’s very exciting to further explore,” says bioinformatician Daoming Wang at the University of Groningen in the Netherlands, who was not involved in the research.

Wang adds that the methods in the study, published on 2 April in Cell1, address thorny challenges in human microbiome research. The research is “really outstanding”, agrees bioinformatician Alexander Kurilshikov at the University of Groningen, who also was not involved in the work.

Missing link

It has been established that the human gut microbiome affects cholesterol levels, and previous research has pointed to microbial enzymes that might be involved. A 2020 study2 identified a bacterial enzyme called ismA that can convert cholesterol into coprostanol, a lipid that is excreted instead of absorbed by the body. People whose gut bacteria made this enzyme had lower cholesterol levels in their blood than did those who did not. This study was published by the same research group — led by gastroenterologist and microbiologist Ramnik Xavier at the Massachusetts General Hospital in Boston — that is responsible for the new finding. Until now, it was not clear which bacteria produced enzymes that metabolize cholesterol.

For the current study, the researchers analysed microbial genomes in stool samples from 1,429 participants in a long-term study of risk factors for cardiovascular disease. The team found many gut-bacteria species, including those in the genus Oscillibacter, that were correlated with lower cholesterol levels. The researchers confirmed their results in participants in two independent studies.

Dark matter of the gut

Next, the team searched two Oscillibacter species and one other bacterial species for genes similar to those known to affect cholesterol metabolism. To do so, the scientists used a deep-learning algorithm that they call a ‘protein language model’. The model assesses not only the features of a gene itself, but also predictions of how the protein encoded by the gene will fold into a 3D structure. The extra information makes the algorithm more sensitive than those that rely on only information about the gene.

They found that the three species have genes encoding proteins that are structurally similar to ismA and other enzymes involved in cholesterol metabolism.

This technique is “innovative and significant”, says Wang, because it provides a method for getting at the ‘dark matter’ of the microbiome: the large number of bacterial genes that aren’t similar enough to any known genes to give clues about their function.

The authors also showed in lab experiments that these three species can metabolize cholesterol. Xavier suspects, on the basis of their data, that there are “many more” Oscillibacter species to be discovered than the 25 identified in the study.

Treatment barriers

If the bacterial species or enzymes could be delivered to the right place in the gut, it might be possible to lower the necessary dose of drugs such as statins to reduce or manage cholesterol levels.

But there are hurdles facing development of such a treatment. Delivering beneficial bacteria has worked very well in treating infections with the common pathogen Clostridium difficile, says Xavier, but C. difficile’s toxin kills off a lot of bacteria, creating space for helpful bacteria. Individuals receiving treatment for high cholesterol would still have their usual gut microbiome community, he says, which could squeeze out the beneficial bacteria.

“It’s a long way off,” says Xavier. But “maybe in patients at risk, we could lower that risk at a much earlier stage”, he says.

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Could the gut give rise to alcohol addiction?

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A monochrome illustration showing a person’s shadow on a bar, when the shadow overlap a beer bottle where the person gut is it turns colourful.

Illustration: Sam Falconer

Andrew Day, a molecular microbiologist at Tufts University in Medford, Massachusetts, is four years sober. His journey to this point inspires his work, which he hopes might help others who are struggling with alcohol.

Nature Outlook: The human microbiome

There are many risk factors associated with alcohol-use disorder (AUD), including mental-health conditions and genetics. But Day is eyeing a more unusual contributor: the gut.

Over the past decade, research has begun to highlight a link between the gastrointestinal microbiome — the microorganisms that live inside our digestive tract — and addiction. Researchers including Day suggest that an imbalance in the intestinal microbiota, known as dysbiosis, might cause the gut to send signals to the brain that promote addiction behaviours. If correct, the gut could become a treatment target for people with AUD. “I could find something that might make it easier for people who might not be as fortunate to maintain sobriety,” says Day, who is studying the theory that high levels of the fungus Candida albicans in the gut contributes to increased alcohol consumption in mice as part of his PhD.

This is a sharp departure from conventional medical approaches to treating addiction. Most drugs for AUD and substance-use disorder (SUD) focus on brain chemistry. Many of them are not very effective. Medications for AUD approved by the US Food and Drug Administration (FDA) include naltrexone and acamprosate. In addition, the European Medicines Agency (EMA) has approved nalmefene. Acamprosate modulates brain receptors such as those that bind γ-aminobutyric acid (GABA), an inhibitory neurotransmitter thought to have a role in withdrawal, craving and impulsive behaviour. Nalmefene and naltrexone modulate opioid receptors, nalmefene reduces alcohol cravings, and naltrexone blocks euphoric sensations associated with alcohol.

According to the US Substance Abuse and Mental Health Services Administration, only 42% of people who receive treatment for any kind of SUD complete that treatment1. Between 40% and 60% of people with an SUD will relapse, and it can take years — sometimes decades — of see-sawing between abstinence and relapse before someone achieves sustained remission. Clearly, there is room for improvement. “We’ve missed the target for 50 years,” says Benjamin Boutrel, a neurobiologist at Lausanne University Hospital in Switzerland. “Mostly because it’s not only a matter of the brain — it’s possibly a matter of the guts, too.”

The gut–brain axis

It is now well known that there is complex communication between the gut and the brain, through the vagus nerve as well as through the endocrine and immune systems. This gut–brain signalling has been suggested to influence addiction-related behaviours in two main ways.

Rear view of white male wearing protective gloves holding up an agar plate

Andrew Day hopes his research will help others who have alcohol-use disorder.Credit: Dr. Carol Kumamoto

The first involves a condition known as leaky gut. Stress, poor diet, food allergies, chemotherapy and other medication, conditions such as inflammatory bowel disease and — perhaps crucially — overuse of alcohol can damage the layer of epithelial cells that line the intestines. This can make the intestinal wall permeable to food particles and bacteria, which can then sneak into the circulatory system.

When this happens, immune cells secrete inflammatory mediators such as cytokines. These proteins can then reach the brain, either through the vagus nerve or by crossing weak areas in the blood–brain barrier, a layer of cells meant to protect the brain from damage.

The subsequent inflammation can affect the brain in several ways that could promote addiction. Cytokines deplete tryptophan, which can lead to reduced production of the mood-regulating hormone serotonin. The brain’s amygdala might sense a threat in the body and increase its activity in response to inflammation. The ventral striatum — the area of the brain related to reward anticipation — might also be ignited. The anterior cingulate cortex — the part of the brain involved in inhibitory control and compulsive behaviour — can also activate during inflammation.

Second, the molecules that gut microbes produce could influence addiction. Some of these are important for brain functioning. The gut bacteria Lactobacillus, for example, can produce GABA; Enterococcus can produce serotonin; and Bacillus can make dopamine. Short-chain fatty acids (SCFAs) released when dietary fibre is fermented by bacteria in the gut also have neuroactive properties.

Gut dysbiosis, and its subsequent impact on GABA, serotonin, dopamine and tryptophan, could, therefore, make a person more susceptible to addiction and mean that they experience more severe withdrawal symptoms than would someone with a healthy gut microbiome.

“The gut microbiome is really important for some organs, including the brain,” says Drew Kiraly, a psychiatrist and physician at Wake Forest University in Winston-Salem, North Carolina. Kiraly has observed associations between dysbiosis and addictive behaviour to stimulants and opioids in rats. He has used antibiotics to deplete rats’ beneficial gut microbes, resulting in “aberrant responses to drugs”. The animals had increased intake of cocaine and fentanyl, he says. “And after withdrawal, they relapse and have higher fentanyl-seeking behaviour.”

Addictive personality

Even before first contact with alcohol or drugs, pre-existing dysbiosis could make someone more vulnerable to addiction, Boutrel says. The imbalance could give rise to traits such as impulsivity, boredom, susceptibility to stress or anxiety, and sensation seeking. “Those who get thrilled with poker playing, with pathological sex, they all need something,” Boutrel says. “There is a vulnerability there that, once that first contact is made, will trigger repetition — and finally, addiction.”

White female wearing white lab coat is standing in front of a woman seated at a computer screen.

Sophie Leclercq is one of few researchers able to study theories about the gut microbiome in people with alcohol-use disorder.Credit: Sophie Leclercq

In 2018, Boutrel and his colleagues put a group of 59 rats through a number of tests designed to assess their vulnerability to AUD2. First, the rodents were trained to self-administer alcohol by pressing a lever. The researchers then tried to gauge the rats’ self-control by introducing a delay to the reward delivery. Some rats pressed the button once, realized that they had to wait, and went about their business. But some would continue pressing over and over, attempting to make the alcohol arrive more quickly — an indication of addiction.

The final test, which Boutrel thinks is most telling, introduced a deterrent — an uncomfortable foot shock every time the animals took the alcohol. For most of the rats, this discouragement was sufficient and they stopped pressing the lever. However, a sizable minority “just didn’t care”, Boutrel says. “They could not stop pressing the lever and accessing the reward, even when they got a punishment.” In total, about 30% of the rats demonstrated vulnerability to AUD.

Having identified a group of vulnerable rats, Boutrel and his colleagues removed alcohol from the rats environment for three months, and then compared the brains and gut microbiomes of the vulnerable rats with those of rats that had proven more resistant to AUD. The team found that the vulnerable rats had more efficient dopamine 1 receptors (which trigger increased reward-seeking and motivation) and less efficient dopamine 2 receptors (which cause impulsivity, and an increased need for immediate rewards and drug administration). They also found differences in the bacterial content of the vulnerable-rat guts — most notably, changes in Lachnospiraceae, Syntrophococcus and other bacteria associated with reductions in dopamine 2 receptors. This, the researchers suggest, is an indication that gut microbiota could affect brain circuits associated with addiction.

Alcohol and other drugs

Sophie Leclercq, a biomedical scientist at the Catholic University of Louvain in Brussels, was an early advocate of the theory about an AUD gut–brain origin, and one of the first to test it in people3. Her aim was to find out whether intestinal permeability was related to character traits that might make people more susceptible to alcohol dependence.

Pink, worm-like structure on a textured blue and black background

Lactobacillus gut bacteria can produce the inhibitory neurotransmitter GABA.Credit: BSIP/UIG Via Getty Images

Leclercq and her colleagues tested the intestinal permeability of 60 people with AUD two days after they began withdrawal. The researchers found that 26 (43%) had high intestinal permeability. At the beginning of the study, everyone with AUD had higher scores of depression, anxiety and craving than did people in the control group. At the end of three weeks of abstinence, the scores of people with low intestinal permeability returned to levels equal to those of the control group. People with high intestinal permeability, however, still scored highly in tests of depression, anxiety and craving, which are directly related to the urge to drink and have a major role in whether people can abstain after detoxification.

“We wanted to see if there was some connection between the gut microbiota and the psychology of AUD, and, indeed, we found that there is a very strong association between dysbiosis, the alteration of the gut microbiota composition, and symptoms like depression, anxiety or grief,” Leclercq says.

Although much of this research is related to people with AUD, Kiraly says that they’ve seen similar results in people who misuse opioids, and cocaine and other stimulants. “Depletion [of microbiota] seems to dysregulate these networks that underlie behavioural changes,” he says.

In 2023, Kiraly and his colleagues looked at whether rats’ microbiomes affected the animal’s drug-seeking behaviours4. In one experiment, rats were given either clean water or water containing the antibiotics neomycin, vancomycin, bacitracin and pimaricin, all of which would deplete their gut microbiota. They were then let into a chamber in which they could push a lever that lit up and provided 0.8 milligrams of cocaine. Later, researchers altered how the lever behaved — now it would light up when pushed, but would have to be pushed more times for the rats to receive cocaine. Researchers found that the rats with depleted gut microbiota were much more likely to press the lever repeatedly to receive cocaine than were the rats given only water.

In a second experiment, both groups of rats were able to self-administer cocaine for two weeks, then detoxed for 21 days. When the rats returned to the cages in which cocaine was available, those receiving antibiotics headed to the lever that originally dosed cocaine twice as quickly as the other rats did. These rats also pressed the lever much more frequently than the control rats did.

“We wanted to study a model of relapse and we saw that microbiome-depleted animals work harder for a drug-related cue than the others did,” Kiraly said. “Lots of people use drugs and not all get to the stage of problematic use. It could be that your microbiome predisposes you.”

Treatment questions

There is still a lot of research that needs to be done before any microbiome-targeted treatment could be offered to people with AUD or another SUD. Researchers don’t yet know, for example, which microbiota are most important, and which gut–brain pathways they need to target. “People have asked me, ‘Can someone just eat yogurt and cure their addiction?’” Kiraly says. “It’s going to be much, much more complicated than that.”

Kiraly would like to see whether probiotics or other treatments could have potential for people with early problematic use but who have not yet progressed to AUD. For instance, some rats in Kiraly’s study were administered SCFAs alongside their antibiotics. Compared with rats that received only antibiotics, those also given SCFAs seemed to retain more Firmicutes and less Proteobacteria (many of which are pathogenic). Strikingly, when the post-detox rats were given the chance to consume cocaine again, those who had received SCFAs behaved like rats with normal gut flora.

Leclercq thinks that 30–40% of cases of AUD might have a gut-related component that could be targeted for treatment. A key challenge is determining exactly which components to target — it is as yet unclear what constitutes a ‘good’ microbiome. Day’s analysis suggests that bacteria such as Lactobacillus, were in abundance in people with AUD, whereas Akkermansia and some others were low.

There is also uncertainty regarding what would be the most effective and easiest part to target of the chain of communication between the gut and brain. Areas such as the nervous system, blood stream or the system surrounding the gut are all candidates.

It is also tricky to find people with AUD who are willing to not only abstain from drinking, but also take part in research, including providing samples of their gut microbiome. Leclercq is one of few researchers able to work with people, instead of rats, because she is affiliated with a hospital with a detoxification clinic. But even she can find it difficult to get enough volunteers for studies. In work assessing the effects of a prebiotic on people with AUD, the number of people with dysbiosis was around half that of those who had healthy guts, making comparisons between the two difficult. Leclercq’s analysis of this aspect of the study is yet to be published.

Despite these issues, Leclercq is moving forward with her research, and is now looking at nutrition as a way to improve the gut microbiome. She is starting a study on polyunsaturated fatty acids — such as those abundant in rapeseed and maize (corn) oils, walnuts, tofu and fatty fish, including salmon and mackerel — and hopes to have results in about two years. She’s also working to correlate which metabolites from food are related to depression, anxiety and craving, and trying to find funding for a study to test these particular nutritional compounds in people.

“Pharmaceutical companies have tried to target GABA, dopamine and serotonin, and these treatments aren’t very efficient because the relapse rate is very high in this disease,” she says. For people with AUD whose guts are contributing to their condition, nutritional interventions, probiotics and prebiotics could eventually improve the odds of success.

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