Does a microbial-endocrine interplay shape love-associated emotions in humans? A hypothesis

In humans (and potentially other species), the presence of lust-associated emotions is considered a powerful motivational force that may be favored by natural selection (18, 19); however, we also recognize that emergent behaviors (not driven by natural selection) also play a role in choosing sexual partners. Our endocrine system plays an important role in regulating sexual desire and behavior through the release and activity of sex hormones (20). The hypothalamus, a structure in the ventral brain, plays a central role in coordinating the endocrine system through its influence on the pituitary gland. For example, the hypothalamus mediates the secretion of the sex hormones testosterone and estradiol from the gonads that control sexual behavior (21). The hypothalamus synthesizes a range of hormones and controls the release of the sex hormones testosterone and estradiol from the gonads through its influence on the pituitary gland (22). Testosterone is commonly associated with male sexual desire, but it also plays a role in female sexual behavior, albeit at lower circulating levels, and can be aromatized into estrogens (23), which also contribute to sexual and emotional responses. It may increase libido and promote sexual arousal in different biological sexes (24). Estradiol, a type of estrogen predominantly considered a female sex hormone, affects sexual motivation in females, particularly around the time of ovulation when levels of estrogen peak (25). Sex hormones interact with the brain’s neural circuits involved in reward, pleasure, and arousal that influence the experience of sexual desire and facilitate the motivation for sexual behavior (26).

Previous research has suggested a link between gut microbiota and the synthesis and secretion of testosterone via the HPG axis (27). The HPG axis is a neuroendocrine pathway that regulates the production and release of sex hormones by the gonads (22). As such, the HPG axis plays a crucial role in controlling reproductive functions, including the development of secondary sexual characteristics, the menstrual cycle in females, and sperm production (indirectly) in males. The HPG axis operates through negative feedback mechanisms (Fig. 1; except during the late follicular phase of the menstrual cycle). Such hormonal negative feedback is a regulatory mechanism in which rising hormone levels inhibit further hormone production to maintain homeostasis (28). When sex hormone levels are low, the hypothalamus synthesizes and releases gonadotropin-releasing hormone (GnRH), which triggers the synthesis and release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary gland (29). Gonadotropins, in turn, stimulate Leydig cells in the testes and follicular cells in the ovaries to produce sex hormones. As sex hormone levels rise, they send signals back to the hypothalamus and pituitary gland, inhibiting the synthesis and release of GnRH and reducing LH and FSH production. An exception to this is during the late follicular phase in the menstrual cycle when high estradiol levels elicit a change from negative to positive feedback of the HPG axis, resulting in a spike in LH and FSH that stimulates ovulation. These feedback loops help regulate the production of sex steroids.

Gut microbiota can regulate androgen production and metabolism (via the release of reactive oxygen species, endotoxins, and metabolites, such as short-chain fatty acids [SCFAs]), thus influencing the HPG axis. The gut microbiome is also involved in the metabolism and intestinal deglucuronidation of dihydrotestosterone (DHT) and testosterone, resulting in extremely high levels of DHT (30, 31). DHT is thought to play a pivotal role in sexual desire and the development of reproductive organs (32). Microbially derived metabolites, including SCFAs (such as butyrate, propionate, and acetate) and secondary bile acids, may cross the intestinal epithelium via monocarboxylate transporters or passive diffusion, subsequently entering circulation and modulating endocrine signaling. Additionally, β-glucuronidase activity within the gut facilitates the deconjugation and reabsorption of testosterone and DHT through enterohepatic circulation, increasing their systemic bioavailability (Fig. 1). Endotoxins such as lipopolysaccharides (LPS) can also activate toll-like receptor 4 on immune cells, leading to inflammation-driven suppression of hypothalamic GnRH secretion, thereby indirectly modulating androgen production. These pathways highlight potential mechanisms by which gut microbiota influence hormone signaling and the physiological regulation of sexual function.

Similar to interactions between androgens and the gut microbiome, research has shown that the gut microbiome is linked to estradiol production. Estradiol affects sexual motivation in females (33) and, thus, likely has a biological influence on lust. Research has shown that the gut microbiome is a regulator of circulating estradiol (26), which has led to the identification of the estrogen-gut microbiome axis. The gut microbiome modulates estradiol levels (conjugated steroids are present in the gut because the human body has metabolized their free forms) through an enzyme called β-glucuronidase that converts estrogens into their active forms by deconjugation (34). However, when the gut microbiome is in a dysbiotic (i.e., “distressed”) state, resulting in reduced microbial diversity, the deconjugation process is hindered, leading to decreased levels of circulating estrogens (35). The estrogen-gut microbiome axis is supported by research that has shown females with hypoactive sexual desire disorder have significantly different gut microbiota and metabolic activity than females in the healthy control group (36). Overall, there is empirical support linking host microbiota, hormones, and lust- and attraction-associated emotions in humans via androgens and estrogens (Fig. 1).

Attraction-associated emotions are thought to be distinct but closely related to lust-associated emotions. While they may occur together, each can occur independently. Attraction involves neural pathways associated with “reward” behaviors, which have been invoked to explain the exhilarating and all-consuming feelings in the early stages of a relationship (34).

Dopamine is released when engaging in enjoyable activities like spending time with loved ones and having (and/or anticipating) sex (37). High levels of dopamine and noradrenaline (norepinephrine) are released during moments of attraction, primarily from the ventral tegmental area (VTA) and locus coeruleus (LC), respectively. Noradrenaline is also produced from the adrenal medulla during sympathetic nervous system activation (i.e., the “fight, flight, or freeze” response). The VTA, a key component of the brain’s reward system, projects dopaminergic neurons to the nucleus accumbens, prefrontal cortex, and amygdala, reinforcing feelings of pleasure, motivation, and reward. Simultaneously, noradrenaline from the LC enhances arousal, alertness, and focus, contributing to feelings of giddiness and euphoria and affecting energy levels and sleep behavior (8). The heightened arousal experienced during attraction might be related to noradrenaline’s role in the so-called “fight, flight, or freeze” response, which maintains alertness during stressful or potentially life-threatening activities (e.g., escaping from predators) (38).

Attraction activates the brain’s dopaminergic reward centers, such as the VTA and caudate nucleus (39). The medial orbitofrontal cortex has been implicated in rewarding experiences, including love and attraction. Takahashi et al. studied the medial orbitofrontal cortex in relation to attraction (37). They found a positive correlation between excitement levels and dopaminergic activation when subjects were exposed to a love treatment but not when exposed to control conditions.

Attraction is linked to reduced serotonin (40), a hormone involved in appetite and mood regulation (41). Moreover, a reduction in serotonin transporters is also observed in people with obsessive-compulsive disorder (42). Therefore, altered serotonin and its link to obsessive traits may contribute to the overpowering infatuation experienced in the early stages of love. Despite being primarily associated with the brain, approximately 95% of the body’s serotonin is produced by enterochromaffin cells of the gut (43). Gut microbiota play a key role in synthesizing and releasing gut-derived serotonin (44). For example, gut microbial metabolites such as SCFAs and lipopolysaccharides influence the serotonergic system (Fig. 2). However, it is not well understood how certain metabolites produced in the gut lumen can make their way to receptors on the intestinal cell surface, transversing not only distance but also getting through two layers of mucus.

SCFAs (primarily butyrate) in the gut lumen stimulate tryptophan hydroxylase-1 expression in enterochromaffin cells (45), which increases serotonin production by the enterochromaffin cells (46). This regulatory role of microbiota on serotonin production suggests a potential link between the gut microbiome and attraction involving neurological (including serotonergic) pathways associated with “reward” behaviors. While the majority of peripheral serotonin does not cross the blood-brain barrier (the selective, semi-permeable barrier that protects the brain by controlling which substances can pass from the bloodstream into the brain tissue), it can influence the brain’s serotonergic system indirectly. Increased serotonin in the gut modulates the vagus nerve, which transmits signals to the brainstem and limbic structures, including the raphe nuclei—the primary source of central serotonin. Through this gut-brain communication, microbiota-induced serotonin production may contribute to the regulation of mood, social bonding, and attraction by influencing central serotonergic pathways involved in reward processing and emotional regulation. Moreover, many bacterial species produce serotonin—for instance, bacteria in the Enterobacteriaceae family of the Proteobacteria phylum (47). Therefore, gut microbiota also have direct roles in serotonin production and, thus, may influence the biological pathways to attraction.

The gut microbiome is linked to dopaminergic neurotransmission (48). Gut microbiota influence the mesocorticolimbic circuit, which is involved in the reward pathway—the same phenomenon associated with attraction. The gut microbiome-dependent production of metabolites can also stimulate the activity of transient receptor potential vanilloid subfamily member 1, which is expressed in sensory neurons (4). These are densely expressed in spinal and cranial neurons. Through this gut-derived stimulation, microbiota can elevate dopamine levels in the brain’s ventral striatum, a structure associated with attraction in humans (4). This highlights a potential pathway for gut microbiota to influence attraction-associated emotions.

Drosophila melanogaster studies suggest that the gut microbiome can impact mating preferences. For instance, Sharon et al. conducted an experiment where a population of D. melanogaster was divided into two groups: one group was reared on a molasses-based medium, and the other on a starch-based medium (49). Subsequently, when the two groups were mixed, the flies raised on molasses preferred mating with other “molasses flies,” whereas the “starch flies” preferred to mate with other starch-reared individuals. This mating preference was closely linked to the gut microbiome. When the flies were treated with antibiotics, the mating preferences were absent, suggesting that the gut microbiome was responsible for driving these preferences. To support this, the researchers inoculated the flies with microbiota from the respective media, and the within-group mating preference was present again. The mechanism by which the gut microbiome influences mating behavior in Drosophila may involve alterations in steroid levels that have similar functions to sex steroids in vertebrates. These changes in hormone levels, in turn, significantly impact the flies’ mating decisions. Research that extends these findings to test the potential of the gut microbiome to affect vertebrate mating preferences is needed.

Attachment often takes precedence in long-term relationships. Attachment plays a role in friendships, parent-infant bonding, social connections, and various other long-term intimacies. In humans and other mammals, oxytocin and vasopressin are the key hormones involved in enhancing biological processes of attachment (50). Oxytocin is often called the “cuddle hormone” and is strongly associated with bond-forming (51). Indeed, microbiome-oxytocin-love associations have been proposed in the past (52, 53). Oxytocin is produced in the hypothalamus (although evidence suggests it is also produced by peripheral organs, including the gastrointestinal tract), which extends into the posterior pituitary and releases this hormone (e.g., during activities such as sex, breastfeeding, and childbirth) and vasopressin (54). Although these activities may seem unrelated, they all serve as precursors to bonding and thus are important for partnerships and familial bonds.

Vasopressin has a role in attachment, particularly in the context of forming and maintaining monogamous pair bonds. Often referred to as the “bonding hormone,” vasopressin is a neuropeptide that influences social behaviors, including attachment and mate choice (55). In males, vasopressin is associated with territorial and aggressive behaviors, often displayed during mate competition. It also affects the brain’s reward and pleasure centers, reinforcing the bond between mates (56). Studies of monogamous prairie voles (Microtus ochrogaster) have shown that higher levels of vasopressin receptors in certain brain nuclei are associated with stronger pair bonding and social attachment (57). In humans, vasopressin levels have been linked to partner bonding and relationship quality (58). Research suggests that individuals with specific genetic variations in vasopressin receptor genes may be more prone to forming strong and lasting attachments to their partners (59). Furthermore, vasopressin interacts with other neurotransmitters and hormones, including oxytocin and dopamine, to regulate social behaviors and emotional responses related to attachment and attraction (60). The interplay between these neurochemicals and their receptors in the brain is thought to shape the complex landscape of human social bonding and romantic relationships.

The gut microbiome is involved in oxytocinergic signaling via the microbiota-gut-brain axis, contributing to the regulation of social behavior (61). Moreover, treating humans with a multispecies probiotic (3× Bifidobacteria and 3× Lactobacilli) increased endogenous oxytocin levels (62), which correlate with gut microbiome composition (e.g., Roseburia, Parabacteroides, Lachnospiraceae NK4A136 group, Ruminococcaceae UCG-013, and Butyricicoccus) (63). These microbes may contribute to oxytocinergic regulation via their production of SCFAs and other neuroactive metabolites. Therefore, the gut microbiome may influence the biological basis of attachment-associated emotions through its effects on oxytocin signaling (Fig. 3). However, further research is needed to elucidate the mechanisms by which microbial communities modulate central oxytocin release and social bonding behaviors.

Microbiota can also potentially influence vasopressin—the other key hormone involved in attachment-associated emotions. The live inoculation of Limosilactobacillus reuteri in rodents altered their vasopressin 1a-receptor in the paraventricular nucleus of the hypothalamus (64). Vasopressin 1a-receptor (also known as arginine vasopressin receptor 1a) is one of the three major receptor types for vasopressin and is present throughout the brain and peripheral organs (65). In mammals, arginine vasopressin is commonly associated with courtship and other social behaviors (66). This further highlights the potential role of microbiota in attachment-associated emotions.

Animal host symbiotic microbiota can affect their decision-making via olfactory pathways. For instance, in a recent experiment with Caenorhabditis elegans, researchers showed that certain gut bacteria can imitate host sensory receptor molecules with the potential to influence the decisions of the host (67). This study focused on a commensal gut bacterium Providencia sp., which produced the neuromodulator tyramine. This tyramine compound interacted with the host’s olfactory system, altering the host’s aversive responses to specific odors. This mechanism appears to promote mutually beneficial food decisions. Here, the gut bacterium manipulates the host animal so that a food source benefits both the animal host and the commensal bacteria. While microbiota-mediated feeding decisions might not directly relate to the attraction component of love, the olfactory system does—via the detection and processing of biochemical attractants (68).

These findings align with the holobiont theory, which conceptualizes the host and its associated microbiota as an integrated ecological unit subject to co-evolutionary processes (69). Rather than viewing the host organism as a standalone entity, the holobiont framework suggests that behavioral and physiological traits—including sensory processing and decision-making—may emerge from interactions between host and microbial genomes (70). In this context, microbial metabolites such as tyramine are potentially co-regulators of host behavior, shaped by evolutionary pressures that favor mutual benefit. This paradigm challenges traditional boundaries between “self” and “other” and suggests that what we often interpret as internally driven behavior may, in fact, be co-authored by our microbial symbionts.

Underappreciating the role that symbiotic microbiota have in influencing a host’s behavior was recently termed the “holobiont blindspot” (71). The authors recently proposed a thought experiment from an olfactory and attraction perspective in humans: (i) modifications or inter-individual differences in the human microbiome occur via environmental disturbances (e.g., via pollution exposures, changes in diet or antibiotic usage); (ii) this may lead to changes in odor perception in the human host; (iii) in turn, this may change host preferences (e.g., human odors as biochemical attractants); (iv) the question then becomes: could the host become less (or more) attracted to another individual due to a microbially mediated driver?; (v) in theory, this could have important relationship implications. This proposed pathway highlights the role that the human gut microbiome could play in complex social relationships because of changes in a host’s biology. In the future, it might be possible to design therapeutic interventions using microbial ecology knowledge (Box 1).