Adverse childhood experiences, such as abuse, neglect or household dysfunction, have been associated with a wide range of physical and mental health problems in adulthood. These include depression, obesity and chronic low-grade inflammation. But how might experiences occurring during childhood continue to influence our health decades later?
One increasingly studied possibility is the microbiota-gut-brain axis (see recent Mental Elf blogs by Robinson S, 2026 and Tien D, 2026). The trillions of microorganisms living in our gut interact with the immune system, metabolism and nervous system, and there is growing interest in how stress and psychological disorders may influence, and be influenced by, the gut microbiome.
Previous research has linked childhood adversity with alterations in the gut microbiota (Maes et al., 2023), obesity (Gardner et al., 2019) and inflammatory markers (Danese et al., 2007), and has identified adverse childhood experiences as an important risk factor for depression (Bai et al., 2024). However, the relationships between childhood adversity, depression, obesity, inflammation and the microbiome are likely to be complex and highly interconnected.
A new study by Hantsoo et al. (2026) in Brain, Behavior and Immunity explores these relationships in pregnant African-American women, asking whether adverse childhood experiences are associated with alterations in the gut microbiome and inflammatory markers, and whether factors such as obesity, depression and diet might help explain these relationships.
Methods
This was a secondary analysis of the Infant Growth and Microbiome (IGram) study, a prospective longitudinal cohort of African-American women and their infants.
The analysis included 107 women in the third trimester of pregnancy. Participants were categorised according to their pre-pregnancy body mass index (BMI) as either healthy weight (BMI <25) or obese (BMI ≥30); women with BMI between 25 and 29.9 were excluded.
Participants completed the 10-item Adverse Childhood Experiences Questionnaire (ACE-Q) and the Centre for Epidemiologic Studies Depression Scale (CES-D). Blood samples were collected to measure inflammatory markers, while stool samples were analysed using shotgun metagenomic sequencing, allowing the researchers to investigate not only which bacteria were present but also the functional potential of the microbial community. Dietary intake was assessed using three 24-hour dietary recalls.
The researchers measured four inflammatory markers: interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-α) and high-sensitivity C-reactive protein (hsCRP). They then used a range of statistical approaches, including path analysis (a method that tests whether the data fit a proposed set of pathways between variables), to explore how adverse childhood experiences, BMI, depressive symptoms, inflammation and the microbiome might be interconnected.
Results
Childhood adversity, body weight and depressive symptoms
ACE-Q scores were positively associated with pre-pregnancy BMI (p=0.005) and depressive symptom severity during pregnancy (p=0.043), which is consistent with previous research.
Childhood adversity and the gut microbiome
There were no significant differences between women with high and low childhood adversity scores in microbiome richness, Shannon diversity (a measure of the variety and balance of bacterial species), or overall taxonomic composition. Bray-Curtis analysis (a measure of how similar bacterial communities are to one another) also found no significant difference in bacterial community composition between the childhood adversity groups. Two individual bacteria initially appeared to be associated with ACE-Q score: Akkermansia muciniphila and Bacteroides fragilis, but these findings did not survive correction for multiple comparisons. Therefore, contrary to the researchers’ original hypothesis, there was no evidence that childhood adversity exposure was directly associated with the overall composition of the gut microbiome.
However, the high childhood adversity group did have lower levels of some pathways related to butyrate production. Butyrate is a short-chain fatty acid produced by gut bacteria and has a range of effects on intestinal and immune function. Importantly, none of the 33 measured stool metabolites showed statistically significant differences after correction for multiple comparisons. These findings therefore suggest a possible alteration in microbial metabolic potential, rather than demonstrating a measurable change in the metabolites themselves.
Depressive symptoms and the microbiome
The picture changed when depressive symptoms were considered. Higher depressive symptom scores were associated with lower abundance of Bifidobacterium longum and higher abundance of Bacteroides thetaiotaomicron (q=0.02 for both, after correction for multiple comparisons).
Depressive symptoms were also associated with differences in the functional potential of the microbiome, including genes involved in carbohydrate metabolism and genes associated with butyrate production.
There was also an interesting ‘double hit’ hypothesis: women with both higher ACE-Q scores and higher depressive symptoms had distinct microbiome communities compared with women with lower ACE-Q scores and fewer depressive symptoms.
Inflammation and path analysis
Childhood adversity scores were associated with IL-1β (q=0.06; the authors counted q<0.1 as significant), but not with IL-6, TNF-α or hsCRP. BMI was correlated with all four inflammatory markers.
Path analysis was then used to explore whether BMI could represent an intermediate pathway linking childhood adversity to inflammation. The model suggested that such adversity was associated with higher pre-pregnancy BMI, which in turn was associated with greater inflammation. A second pathway linked adverse childhood experiences with depressive symptoms, which were associated with differences in gut microbiome composition.
Dietary interactions
Among women with higher childhood adversity exposure, greater monounsaturated fatty acid intake was associated with lower IL-6 levels. There were also interactions between adversity status and sugar and whole-grain intake in relation to microbiome-related measures and microbial enzymes.
These findings suggest that childhood adversity might not simply be associated with a particular microbiome, but could potentially influence how the microbiome responds to dietary exposures. However, these analyses were exploratory and should be interpreted cautiously.
Conclusions
This study provides an interesting glimpse into the complex relationships between childhood adversity, depression, obesity, inflammation and the gut microbiome in pregnant women. Its findings do not support a simple model in which adverse childhood experiences directly alter the gut microbiome. Instead, they suggest potentially distinct pathways involving BMI and inflammation on one hand, and depressive symptoms and the microbiome on the other.
The gut microbiome may ultimately prove to be one piece of the puzzle linking early-life experiences with later mental and physical health. The researchers highlight the complexity of these interconnected biological pathways and the need for further research to understand them.
Strengths and limitations
As a psychiatrist with an interest in the microbiota-gut-brain axis, I found this an interesting study. It brings together several important strands of research, but, as always with observational microbiome studies, there are some important caveats.
Strengths
Firstly, the microbiome assessment was comprehensive. Rather than relying on 16S sequencing (a method that mainly identifies which bacteria are present), the researchers used shotgun metagenomic sequencing. This provides information about both microbial composition and the genes present. Secondly, there is strength in the multi-omics approach. This is particularly valuable in microbiome research, where many potentially important confounders interact with one another. Thirdly, the use of path analysis provided a helpful framework for considering how adverse childhood experiences, BMI, depression, inflammation and the microbiome might interact.
Limitations
Firstly, I did not see evidence of pre-registration of the study. With such a large number of possible analyses, pre-registration would make it easier for readers to distinguish confirmatory findings from hypothesis-generating ones and ultimately help improve the reliability, quality, and replicability of the research findings. Secondly, why exclude women who were overweight (with BMI between 25 and 29.9)? Given the central role of BMI in the proposed pathway, this might limit generalisability.
The researchers also excluded participants taking certain medications including several psychotropics and medications known to affect weight or insulin sensitivity. When studying the gut microbiome, it is important to consider the influence of commonly used medications, particularly proton pump inhibitors (PPIs) and other acid-suppressing medications that can have a significant impact on microbiome composition. Gastrointestinal reflux is common during pregnancy, so the use of PPIs or antacids may be important confounding factors that do not appear to have been taken into account.
Three participants had taken antibiotics within three weeks of stool collection, which can substantially alter the gut microbiome. The authors statistically adjusted for antibiotic use, but I wondered whether a sensitivity analysis excluding these three participants might have been useful.
Finally, although I liked the use of path analysis, in this cross-sectional study it cannot establish temporal sequence or prove mediation. This is particularly important given the paper’s title, which states that the effects of adverse childhood experiences on the microbiome and inflammation ‘is mediated by obesity and depression.’ I think this wording overstates the conclusions.
Other limitations include the relatively small sample, with an imbalance between the low- and high-childhood adversity groups. The authors also used the CES-D rather than a pregnancy-specific depression measure such as the Edinburgh Postnatal Depression Scale and they acknowledge this. In addition, the participants were all African-American women, and the findings therefore cannot be generalised to other populations.
Implications for practice
So, should we be recommending microbiome-targeted interventions to pregnant women who have experienced childhood adversity? Unfortunately, we do not yet know the answer to this question!
The findings are mechanistically interesting, but they do not demonstrate that altering the microbiome will improve depression, inflammation or physical health in people with a history of adverse childhood experiences. What the study does reinforce is the importance of taking a holistic approach to the long-term consequences of childhood adversity. For people with a history of adversity, this may mean paying attention not only to psychological symptoms but also to physical health, metabolic risk, diet and other lifestyle factors.
The finding linking childhood adversity, BMI and inflammation is particularly relevant during pregnancy, when metabolic and inflammatory health have implications for both mother and infant. However, it would be premature to conclude from this study that weight loss or dietary interventions will reverse the biological effects of such adversity. Similarly, the association between depressive symptoms and the microbiome is interesting, but it does not tell us whether depression changes the microbiome, the microbiome contributes to depression, or whether both are influenced by other factors.
Future studies need to move beyond cross-sectional associations. Longitudinal studies following people from childhood through adulthood would help establish the temporal sequence between adversity, mental health, metabolic health and microbiome changes. Ideally, these studies would repeatedly assess diet, medication, physical health, psychological symptoms, microbiome composition and microbial function. Ultimately, intervention studies will be needed to determine whether modifying any of these pathways actually improves outcomes.
The gut microbiome may be one piece of the puzzle, but we are not yet at the point where it can be translated into microbiome-based treatments for the consequences of childhood adversity. Perhaps the most useful message from this study is that the biology of adversity is complex, and our interventions need to be equally holistic and nuanced.
For the rapidly evolving field of microbiome-gut-brain research, this is an important reminder that association is not causation and biological complexity should not be mistaken for evidence of a causal mechanism.
Statement of interests
Mary Butler (she/her) has no conflicts of interest to declare. Artificial intelligence (ChatGPT, OpenAI) was used to assist in the creation of the above figure. The author reviewed and approved the final version.
Editor
Edited by Éimear Foley. Claude assisted with language refinement and formatting during the editorial phase.
Links
Primary paper
Liisa Hantsoo, Eileen Ford, Elliot S Friedman, Fuhua Hao, Andrew D Patterson, Kyle Bittinger, Gary D Wu, Babette S Zemel, Ceylan Tanes (2026) The impact of adverse childhood experiences on gut microbiota and markers of inflammation is mediated by obesity and depression. Brain, Behavior, and Immunity 2026 134 106479. https://doi.org/10.1016/j.bbi.2026.106479
Other references
Bai, Y., Shu, C., Hou, Y. and Wang, G.-H. (2024) ‘Adverse childhood experience and depression: the role of gut microbiota’, Frontiers in Psychiatry, Volume 15 – 2024.
Danese, A., Pariante, C. M., Caspi, A., Taylor, A. and Poulton, R. (2007) ‘Childhood maltreatment predicts adult inflammation in a life-course study’, Proc Natl Acad Sci U S A, 104(4), pp. 1319-24.
Gardner, R., Feely, A., Layte, R., Williams, J. and McGavock, J. (2019) ‘Adverse childhood experiences are associated with an increased risk of obesity in early adolescence: a population-based prospective cohort study’, Pediatric Research, 86(4), pp. 522-528.
Maes, M., Vasupanrajit, A., Jirakran, K., Klomkliew, P., Chanchaem, P., Tunvirachaisakul, C., Plaimas, K., Suratanee, A. and Payungporn, S. 2023. Adverse childhood experiences and reoccurrence of illness impact the gut microbiome, which affects suicidal behaviours and the phenome of major depression: Towards enterotypic phenotypes. United Kingdom: Cambridge University Press.
Robinson S. What your microbiome reveals about immune health, and what it doesn’t. The Mental Elf, 14 Sep 2026.
Tien D. Vitamin C, gut bacteria, and mental vitality: early findings. The Mental Elf, 23 Feb 2026.