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The human gut microbiome plays an important role in the maturation of the neural, immune, and endocrine systems. Research data from animal models shows that gut microbiota communicate with the host's brain in an elaborate network of signaling pathways, including the vagus nerve. Part of the microbiome's influence extends to the behavioral and social development of its host. As a social species, a human's ability to communicate with others is imperative to their survival and quality of life. Current research explores the gut microbiota's developmental influence as well as how these gut-brain pathways can be leveraged to alleviate the social symptoms associated with various neurodevelopmental and psychiatric diseases. One intriguing vein of research in animal models centers on probiotic treatment, which leads to downstream increased circulation of endogenous oxytocin, a neuropeptide hormone relevant to sociability. Further research may lead to therapeutic applications in humans, particularly in the early stages of their lives.

This narrative describes a personal journey that led to the discovery of a profound connection between microbial symbionts and oxytocin. Pivotal oxytocin discoveries began to emerge in 2011 while this researcher’s multidisciplinary team explored gut microbial priming of the immune system and perinatal health. Inspired by oxytocin's role in early life events of milk release, neural connections, and social bonding, the team hypothesized a symbiotic relationship between microbes and oxytocin. Scientific experiments demonstrated that specific milk-borne microbes boosted oxytocin levels through a vagus nerve-mediated gut-brain pathway, affecting immune functions and wound healing capacity in the host animal. The exploration then expanded to microbial impacts on reproductive fitness, body weight, and even mental health. Overarching hypotheses envisioned a nurturing symbiosis promoting survival and societal advancement. Ultimately, this oxytocin-mediated partnership between microbes and mammals is portrayed as a harmonious legacy of neurological stability, empathy, and universal wisdom, transcending generations. The author's personal journey underscores the beauty and inspiration found in her scientific exploration.

The mammalian host microbiome affects many targets throughout the body, at least in part through an integrated gut-brain-immune axis and neuropeptide hormone oxytocin. It was discovered in animal models that microbial symbionts, such as Lactobacillus reuteri, leverage perinatal niches to promote multigenerational good health and reproductive fitness. While roles for oxytocin were once limited to women, such as giving birth and nurturing offspring, oxytocin is now also proposed to have important roles linking microbial symbionts with overall host fitness and survival throughout the evolutionary journey.

Diener, Hoge et al. show that a third of mice exhibit tolerance to a high dose of the β-lactam antibiotic cefoperazone, independent of antibiotic treatment duration or dietary phytochemical amendment. They find that non-responder microbiota upregulates antimicrobial tolerance genes and downregulates central metabolism without altering community composition or diversity, providing insights into the mechanisms of community-wide antibiotic tolerance.

Summary: Interest in manipulating the gut microbiota to treat disease has led to a need for understanding how organisms can establish themselves when introduced into a host with an intact microbial community. Here, we employ the concept of orthogonal niche engineering: a resource typically absent from the diet, seaweed, creates a customized niche for an introduced organism. In the short term, co-introduction of this resource at 1% in the diet along with an organism with exclusive access to this resource, Bacteroides plebeius DSM 17135, enables it to colonize at a median abundance of 1% and frequently up to 10 or more percent, both on pulsed and constant seaweed diets. In a two-month follow-up after the initial treatment period, B. plebeius stops responding to seaweed in mice initially on the constant seaweed diet, suggesting treatment regime will affect controllability. These results offer potential for diet-based intervention to introduce and control target organisms. : Kearney et al. show that co-introducing a bacterial commensal along with a resource to which it has exclusive access enables it to grow to high abundances in the mouse gut microbiota. Long-term response of the commensal to substrate depends on the frequency of substrate exposure during an initial diet period. Keywords: bacteroides, gut microbiome, gut microbiota, orthogonal niche, seaweed, microbial ecology, microbiome modulation, microbial engraftment

Spiritual journeys unveil our inner wisdom to help us navigate traumatic life events. Scientific evidence implicates a gut–immune–brain axis in our sense of self, raising the possibility that our microbial partners and hormone oxytocin offer a sense of connectedness and liberate our ancestral archives to sustain us during challenging times.

Chronic inflammation of mucosal surfaces renders them increasingly susceptible to epithelial cancers both in humans and mice. We have previously shown that anti-inflammatory CD4࠾㥄ᥨ࠽ regulatory (Treg or TR) lymphocytes down-regulate inflammation and block development of bacteria-triggered colitis and colorectal cancer (CRC) in 129/SvEv Rag2−/− mice. Interestingly, TR cells collected from Interleukin (IL)-10-deficient cell donors not only failed to suppress carcinogenesis but instead promoted invasive mucinous colonic carcinoma with a strong gender bias expressing in male mice. We found we show that peritoneal invasion in this model is dependent on pleiotropic cytokine IL-6. Mucinous carcinoma arose rapidly and consistently after treatment with IL10−/− TR cells, which were found to express Foxp3 and localize throughout tumor tissue. Carcinogenesis was rapidly reversible with transfer of wild type IL10-competent TR cells. Likewise, treatment with IL10-Ig fusion protein was sufficient to revert the lesions histologically, and restore inflammatory cytokine and oncogene expression to base line levels. These studies indicate an essential role for IL 6 in this CRC phenotype. Furthermore, immune-competent TR cells were important not only for preventing pathology but also for constructive remodeling of bowel following tumorigenic microbial insults. These data provide insights into etiopathogenesis of inflammation-associated epithelial invasion and maintenance of epithelial homeostasis. [ABSTRACT FROM AUTHOR]

The decline of circulating testosterone levels in aging men is associated with adverse health effects. During studies of probiotic bacteria and obesity, we discovered that male mice routinely consuming purified lactic acid bacteria originally isolated from human milk had larger testicles and increased serum testosterone levels compared to their age-matched controls. Further investigation using microscopy-assisted histomorphometry of testicular tissue showed that mice consuming Lactobacillus reuteri in their drinking water had significantly increased seminiferous tubule cross-sectional profiles and increased spermatogenesis and Leydig cell numbers per testis when compared with matched diet counterparts This showed that criteria of gonadal aging were reduced after routinely consuming a purified microbe such as L. reuteri. We tested whether these features typical of sustained reproductive fitness may be due to anti-inflammatory properties of L. reuteri, and found that testicular mass and other indicators typical of old age were similarly restored to youthful levels using systemic administration of antibodies blocking pro-inflammatory cytokine interleukin-17A. This indicated that uncontrolled host inflammatory responses contributed to the testicular atrophy phenotype in aged mice. Reduced circulating testosterone levels have been implicated in many adverse effects; dietary L. reuteri or other probiotic supplementation may provide a viable natural approach to prevention of male hypogonadism, absent the controversy and side-effects of traditional therapies, and yield practical options for management of disorders typically associated with normal aging. These novel findings suggest a potential high impact for microbe therapy in public health by imparting hormonal and gonad features of reproductive fitness typical of much younger healthy individuals.

Wound healing capability is inextricably linked with diverse aspects of physical fitness ranging from recovery after minor injuries and surgery to diabetes and some types of cancer. Impact of the microbiome upon the mammalian wound healing process is poorly understood. We discover that supplementing the gut microbiome with lactic acid microbes in drinking water accelerates the wound-healing process to occur in half the time required for matched control animals. Further, we find that Lactobacillus reuteri enhances wound-healing properties through up-regulation of the neuropeptide hormone oxytocin, a factor integral in social bonding and reproduction, by a vagus nerve-mediated pathway. Bacteria-triggered oxytocin serves to activate host CD4+Foxp3+CD25+ immune T regulatory cells conveying transplantable wound healing capacity to naive Rag2-deficient animals. This study determined oxytocin to be a novel component of a multi-directional gut microbe-brain-immune axis, with wound-healing capability as a previously unrecognized output of this axis. We also provide experimental evidence to support long-standing medical traditions associating diet, social practices, and the immune system with efficient recovery after injury, sustained good health, and longevity.

A role for microbes has been suspected in prostate cancer but difficult to confirm in human patients. We show here that a gastrointestinal (GI) tract bacterial infection is sufficient to enhance prostate intraepithelial neoplasia (PIN) and microinvasive carcinoma in a mouse model. We found that animals with a genetic predilection for dysregulation of wnt signaling, Apc (Min/+) mutant mice, were significantly susceptible to prostate cancer in an inflammation-dependent manner following infection with Helicobacter hepaticus. Further, early neoplasia observed in infected Apc (Min/+) mice was transmissible to uninfected mice by intraperitoneal injection of mesenteric lymph node (MLN) cells alone from H. hepaticus-infected mutant mice. Transmissibility of neoplasia was preventable by prior neutralization of inflammation using anti-TNF-α antibody in infected MLN donor mice. Taken together, these data confirm that systemic inflammation triggered by GI tract bacteria plays a pivotal role in tumorigenesis of the prostate gland.

Radiant skin and hair are universally recognized as indications of good health. However, this 'glow of health' display remains poorly understood. We found that feeding of probiotic bacteria to aged mice induced integumentary changes mimicking peak health and reproductive fitness characteristic of much younger animals. Eating probiotic yogurt triggered epithelial follicular anagen-phase shift with sebocytogenesis resulting in thick lustrous fur due to a bacteria-triggered interleukin-10-dependent mechanism. Aged male animals eating probiotics exhibited increased subcuticular folliculogenesis, when compared with matched controls, yielding luxuriant fur only in probiotic-fed subjects. Female animals displayed probiotic-induced hyperacidity coinciding with shinier hair, a feature that also aligns with fertility in human females. Together these data provide insights into mammalian evolution and novel strategies for integumentary health.

A recent epidemiological study showed that eating 'fast food' items such as potato chips increased likelihood of obesity, whereas eating yogurt prevented age-associated weight gain in humans. It was demonstrated previously in animal models of obesity that the immune system plays a critical role in this process. Here we examined human subjects and mouse models consuming Westernized 'fast food' diet, and found CD4(+) T helper (Th)17-biased immunity and changes in microbial communities and abdominal fat with obesity after eating the Western chow. In striking contrast, eating probiotic yogurt together with Western chow inhibited age-associated weight gain. We went on to test whether a bacteria found in yogurt may serve to lessen fat pathology by using purified Lactobacillus reuteri ATCC 6475 in drinking water. Surprisingly, we discovered that oral L. reuteri therapy alone was sufficient to change the pro-inflammatory immune cell profile and prevent abdominal fat pathology and age-associated weight gain in mice regardless of their baseline diet. These beneficial microbe effects were transferable into naïve recipient animals by purified CD4(+) T cells alone. Specifically, bacterial effects depended upon active immune tolerance by induction of Foxp3(+) regulatory T cells (Treg) and interleukin (Il)-10, without significantly changing the gut microbial ecology or reducing ad libitum caloric intake. Our finding that microbial targeting restored CD4(+) T cell balance and yielded significantly leaner animals regardless of their dietary 'fast food' indiscretions suggests population-based approaches for weight management and enhancing public health in industrialized societies.