孕期童年逆境、抑郁、肥胖与肠道菌群：Hantsoo 等研究揭示的复杂关联

研究关注的问题

童年遭受虐待、忽视或家庭功能失调，与成年后的抑郁、肥胖和慢性低度炎症相关。但这些经历如何在数十年后继续影响健康，机制仍不清楚。肠道菌群—肠—脑轴是近年被频繁讨论的一条可能通路：肠道微生物与免疫、代谢和神经系统互动，压力与心理障碍也可能反过来影响菌群。

研究设计与对象

Hantsoo 等（2026）的研究发表于《Brain, Behavior and Immunity》，是对“婴儿生长与微生物组”（IGram）前瞻性队列的二次分析，纳入107名处于孕晚期的非裔美国女性。参与者按孕前BMI分为健康体重（<25）与肥胖（≥30），BMI在25至29.9之间者被排除。研究使用10项童年逆境问卷（ACE-Q）和流行病学研究中心抑郁量表（CES-D），采集血样测四种炎症标志物，用鸟枪法宏基因组测序分析粪便，并通过三次24小时膳食回顾评估饮食。

主要发现

童年逆境评分与孕前BMI（p=0.005）及孕期抑郁症状严重程度（p=0.043）呈正相关，与此前研究一致。但与研究者原假设相反，高、低童年逆境组在菌群丰富度、Shannon多样性、整体分类组成和Bray-Curtis群落相似性上均无显著差异；两种初看相关的细菌在多重比较校正后不再显著。高逆境组仅在某些与丁酸生成相关的通路上水平较低，而33种粪便代谢物经校正后均无显著差异，提示可能是微生物代谢潜能的改变，而非代谢物本身的可测变化。

抑郁症状则与菌群关联更明显：抑郁评分较高者长双歧杆菌丰度较低、多形拟杆菌丰度较高（校正后q=0.02），并伴随碳水化合物代谢和丁酸生成相关基因的功能潜能差异。同时具有较高逆境评分和较多抑郁症状的女性，其菌群群落也与其他女性不同，作者称之为“双重打击”假设。

炎症与路径分析

童年逆境评分与IL-1β相关（q=0.06，作者将q<0.1计为显著），但与IL-6、TNF-α和hsCRP无关；BMI则与全部四种炎症标志物相关。路径分析提示，童年逆境可能与较高的孕前BMI相关，而后者又与更强的炎症相关，即肥胖可能是连接童年逆境与炎症的中间环节。这属于统计模型的推测，不能读作因果证明。

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.

 Photo credits

• Photo by Trust “Tru” Katsande on Unsplash
• Photo by Dexswaggerboy on Unsplash
• Image created by Mary Butler using ChatGPT, OpenAI.
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