The microbiome, especially that present in the gut, has emerged as a key modulator of animal behavior. However, the extent of its influence across species and behavioral repertoires, as well as the underlying mechanisms, remains poorly understood. Increasing evidence suggests that microbial metabolites play an important role in driving behavioral variation. In this review, we synthesize findings from vertebrates to invertebrates, spanning both model and non-model organisms, to define key groups of microbial-derived metabolites involved in modulating seven distinct behaviors: nutrition, olfaction, circadian rhythms, reproduction, locomotion, aggression, and social interactions. We discuss how these microbial metabolites interact with host chemosensory systems, neurotransmitter signaling, and epigenetic modifications to shape behavior. Additionally, we highlight critical gaps in mechanistic understanding, including the need to map additional host receptors and signaling pathways, as well as the untapped potential of microbial biosynthetic gene clusters as sources for novel bioactive compounds. Advancing these areas will enhance understanding of the microbiome's role in behavioral modulation and open new avenues for microbiome-based interventions for behavioral disorders.

Serotonin is one of the most potent gastrointestinal, peripheral, and neuronal signaling molecules and plays a key role in regulating energy metabolism. Accumulating evidence has shown the complex interplay between gut microbiota and host energy metabolism. In this review, we summarize recent findings on the role of gut microbiota in serotonin metabolism and discuss the complicated mechanisms by which serotonin, working in conjunction with the gut microbiota, affects total body energy metabolism in the host. Gut microbiota affects serotonin synthesis, storage, release, transport, and catabolism. In addition, serotonin plays an indispensable role in regulating host energy homeostasis through organ crosstalk and microbe-host communication, particularly with a wide array of serotonergic effects mediated by diverse serotonin receptors with unique tissue specificity. This fresh perspective will help broaden the understanding of serotonergic signaling in modulating energy metabolism, thus shedding light on the design of innovative serotonin-targeting strategies to treat metabolic diseases.

The invasion of Eimeria causes damage to the intestinal barrier, nutrient leakage, and microbial imbalance in poultry. We aimed to investigate the effects of Eimeria infection on growth performance, intestinal integrity, and cecal microbial diversity and composition of yellow broilers. A total of 180 male yellow broilers were randomly divided into an unchallenged control and an Eimeria challenge treatment group within 18 floor pens (10 chicks/pen, 9 replicate pens/group). On day 10, 90 chicks received a cocktail of E. maxima, E. acervulina, and E. tenella oocysts (105/chick) to induce coccidial infection, and the other 90 received an aliquot of PBS. The Eimeria challenge resulted in increased bird feed consumption and FCR from day 11 to 21 (all P < 0.01). Higher fecal Eimeria counts, duodenal, jejunal, and cecal lesions were observed in the challenge group on day 12, 15, 15, 18 respectively (all P < 0.05). Furthermore, the infected birds had larger livers and small intestines, deeper villus crypt, and decreased expression of Claudin-1 on day 21 (all P < 0.05). The 16S rRNA sequencing indicated that alpha diversity (Sobs, Shannon, Simpson, Ace, or Chao) of cecal microbials was not affected by Eimeria challenge (all P > 0.05). However, the PCoA and LEfSe analyses indicated that the Eimeria challenge altered microbial distribution by decreasing the abundance of Firmicutes and enriching the abundance of Proteobacteria at the phylum level. At the genus level, Clostridia vadin BB60 and Lachnospiraceae NK4A136 group were reduced, while Escherichia-Shigella were enriched in the challenged yellow broilers (all P < 0.05). Correlation analyses demonstrated that the birds with higher Lachonospiraceae NK4A136 group and Clostridia vadin BB60, and lower Escherichia-Shigella in their cecal content gained more BW and reached a lower FCR from day 11 to 21 (all P < 0.05). In conclusion, Eimeria infection compromised feed efficiency of yellow broilers by damaging intestinal barrier and shifting cecal microbiota towards colonizers associated with poor performance. Restoring the dysbiotic microbiome could be a potential strategy for improving feed efficiency in yellow broilers under coccidial challenge.

Red Cooked Sauce (RCS) and Red Raw Sauce (RRS) are a mixture of natural crops that have a promising content of bioactive compounds (BC). The aim was to determine the effect of the indigestible fraction (IF) during the colonic fermentation in RCS and RRS by studying the two-way relationship between gut microbiota composition and microbial metabolites produced from BC fermented in the TNO in vitro dynamic model of the human colon (TIM-2). Total BC in undigested and predigested RRS, 957 and 715 mg/100 g DW, respectively, was significantly higher (p < 0.05) than in the RCS, 571 and 406 mg/100 g DW, respectively. Catenibacterium and Holdemanella increased during RCS fermentation, while 13 genera showed a clear positive correlation with most microbial phenolic metabolites. Our findings suggest that the mechanisms, pathways, and enzymes involved in producing microbial metabolites exhibited uniqueness among bacterial taxa, even within shared genus/family classifications.

The objective of this study was to investigate the effects of starch structure (Amylopectin/Amylose, AP/AM) in a low-protein diet on production performance, nitrogen utilization efficiency, and cecal flora in laying hens. Four hundred eighty 45-wk-age Hy-Line Gray laying hens were randomly allocated to five dietary groups and subjected to a 12-wk feeding trial. The AP/AM ratios of the five experiment diets were 1.0, 1.5, 2.0, 3.0, and 4.0. The results indicated that compared to other groups, laying hens fed with AP/AM 4.0 diets showed significantly improved average egg weight and feed conversion ratio (P < 0.05). Furthermore, as the AP/AM ratio increased, there was a significant linear enhancement in intestinal amino acids apparent digestibility, apparent metabolizable energy, and villus area (P < 0.05). Compared to the high AP groups, high-AM diets significantly increased eggshell thickness, crude protein digestibility, and reduced energy supply from amino acid oxidation in ileum (P < 0.05). Additionally, moderate-AM diets enriched with short-chain fatty acid-producing bacteria in the cecum, such as Lactobacillus, Rikenellaceae_RC9_gut_group, and Christensenellaceae_R-7_group, which are associated with the promoting nitrogen utilization. These findings may offer useful information on optimizing starch structure for the design of food products and relevant therapies due to the potential effects on nutrient metabolism and gut homeostasis.

The gut-brain axis is regarded as a bidirectional communication system that integrates signals from the gut microbiome into behavioral aspects and vice versa. The aim of the present study was to investigate the gut microbiome-behavior interaction in relation to aggression. For that, male rats from a group-housed colony were individually housed with a female to become territorial. Next, a coping strategy was assigned to them, by evaluating their aggression levels against an intruder, during the Resident-Intruder test (RI). To investigate if their microbiome would change as a consequence of the developed coping strategy, fecal samples were collected before and after the RI test. We found that the relative abundances of Ruminococcaceae UCG-5 and Gram-negative bacterium cTPY-13 in rats sampled before the RI test were negatively correlated with the aggression that was demonstrated during the RI test. After the RI test, several bacterial taxa could be assigned to each coping strategy, with Clostridium sensu stricto 1 being strongly associated with less aggressive rats and higher abundances of Bifidobacterium. Furthermore, the family of Lachnospiraceae was not only associated with more aggressive rats, but functional prediction analysis found it to be the main contributor of betaine reductase; an enzyme catalyzing betaine production that was indicative of aggressive rats. This amino acid derivative, which has been connected with higher energy and testosterone levels, could potentially explain the connection of Lachnospiraceae with demonstrated aggression. Overall, our data revealed that the gut bacterial communities are responsive to the imposed social challenge of building and defending territoriality in co-habitation with a female. At the same time, predisposing microbiome characteristics may have predictive value for the development of a coping strategy.

Numerous studies have evidenced that neuropsychiatric disorders (mental illness and emotional disturbances) with aggression (or violence) pose a significant challenge to public health and contribute to a substantial economic burden worldwide. Especially, social disorganization (or social inequality) associated with childhood adversity has long-lasting effects on mental health, increasing the risk of developing neuropsychiatric disorders. Intestinal bacteria, functionally as an endocrine organ and a second brain, release various immunomodulators and bioactive compounds directly or indirectly regulating a host's physiological and behavioral homeostasis. Under various social challenges, stress-induced dysbiosis increases gut permeability causes serial reactions: releasing neurotoxic compounds, leading to neuroinflammation and neuronal injury, and eventually neuropsychiatric disorders associated with aggressive, violent, or impulsive behavior in humans and various animals via a complex bidirectional communication of the microbiota-gut-brain (MGB) axis. The dysregulation of the MGB axis has also been recognized as one of the reasons for the prevalence of social stress-induced injurious behaviors (feather pecking, aggression, and cannibalistic pecking) in chickens. However, existing knowledge of preventing and treating these disorders in both humans and chickens is not well understood. In previous studies, we developed a non-mammal model in an abnormal behavioral investigation by rationalizing the effects of gut microbiota on injurious behaviors in chickens. Based on our earlier success, the perspective article outlines the possibility of reducing stress-induced injurious behaviors in chickens through modifying gut microbiota via cecal microbiota transplantation, with the potential for providing a biotherapeutic rationale for preventing injurious behaviors among individuals with mental disorders via restoring gut microbiota diversity and function.

Monosodium glutamate (MSG), an umami substance, stimulates the gut-brain axis communication via gut umami receptors and the subsequent vagus nerves. However, the brain mechanism underlying the effect of MSG ingestion during the developmental period on aggression has not yet been clarified. We first tried to establish new experimental conditions to be more appropriate for detailed analysis of the brain, and then investigated the effects of MSG ingestion on aggressive behavior during the developmental stage of an ADHD rat model.

Long-Evans, WKY/Izm, SHR/Izm, and SHR-SP/Ezo were individually housed from postnatal day 25 for 5 weeks. Post-weaning social isolation (PWSI) was given to escalate aggressive behavior. The resident-intruder test, that is conducted during the subjective night, was used for a detailed analysis of aggression, including the frequency, duration, and latency of anogenital sniffing, aggressive grooming, and attack behavior. Immunohistochemistry of c-Fos expression was conducted in all strains to predict potential aggression-related brain areas. Finally, the most aggressive strain, SHR/Izm, a known model of attention-deficit hyperactivity disorder (ADHD), was used to investigate the effect of MSG ingestion (60 mM solution) on aggression, followed by c-Fos immunostaining in aggression-related areas. Bilateral subdiaphragmatic vagotomy was performed to verify the importance of gut-brain interactions in the effect of MSG.

The resident intruder test revealed that SHR/Izm rats were the most aggressive among the four strains for all aggression parameters tested. SHR/Izm rats also showed the highest number of c-Fos + cells in aggression-related brain areas, including the central amygdala (CeA). MSG ingestion significantly decreased the frequency and duration of aggressive grooming and attack behavior and increased the latency of attack behavior. Furthermore, MSG administration successfully increased c-Fos positive cell number in the intermediate nucleus of the solitary tract (iNTS), a terminal of the gastrointestinal sensory afferent fiber of the vagus nerve, and modulated c-Fos positive cells in the CeA. Interestingly, vagotomy diminished the MSG effects on aggression and c-Fos expression in the iNTS and CeA.

MSG ingestion decreased PWSI-induced aggression in SHR/Izm, which was mediated by the vagus nerve related to the stimulation of iNTS and modulation of CeA activity.

Polysaccharides derived from Alhagi camelorum Fisch possess diverse activities, making them a potential prebiotic candidates for enhancing lamb health. This study investigated the immunomodulatory effects of Alhagi camelorum Fisch polysaccharides from Aksu (AK) and Shanshan (SS) regions on sheep lambs. The results showed that sheep lambs in the SS group exhibited significantly increased (p < 0.05) average daily gain, levels of growth hormone (GH), insulin (INS), IgA and IgM, and cytokines IL-4, IL-10, IL-17, TNF-α and IFN-γ compared to those in the control check (CK) group. Moreover, the SS treatment significantly increased the diversity and abundance of beneficial bacteria, while concurrently diminishing the prevalence of harmful bacteria. Additionally, it modulated various metabolic pathways, promoted lamb growth, improved immunity, reduced the risk of gastrointestinal disease and improved the composition of gastrointestinal microbiota. In summary, our findings highlight the potential of SS treatment in enhancing gastrointestinal health of sheep lambs by improving intestinal function, immunity, and gut microbiome. Consequently, these results suggest that Alhagi camelorum Fisch polysaccharides derived from Shanshan regions holds promising potential as a valuable intervention for optimizing growth performance in sheep lambs.

The brain-gut axis forms a bidirectional communication system between the gastrointestinal (GI) tract and cognitive brain areas. Disturbances to this system in disease states such as inflammatory bowel disease have consequences for neuronal activity and subsequent cognitive function. The gut-microbiota-brain axis refers to the communication between gut-resident bacteria and the brain. This circuits exists to detect gut microorganisms and relay information to specific areas of the central nervous system (CNS) that in turn, regulate gut physiology. Changes in both the stability and diversity of the gut microbiota have been implicated in several neuronal disorders, including depression, autism spectrum disorder Parkinson's disease, Alzheimer's disease and multiple sclerosis. Correcting this imbalance with medicinal herbs, the metabolic products of dysregulated bacteria and probiotics have shown hope for the treatment of these neuronal disorders. In this review, we focus on recent advances in our understanding of the intricate connections between the gut-microbiota and the brain. We discuss the contribution of gut microbiota to neuronal disorders and the tangible links between diseases of the GI tract with cognitive function and behaviour. In this regard, we focus on irritable bowel syndrome (IBS) given its strong links to brain function and anxiety disorders. This adds to the growing body of evidence supporting targeted therapeutic strategies to modulate the gut microbiota for the treatment of brain/mental-health-related disease.

Accumulating evidence from human trials and rodent studies has indicated that modulation of gut microbiota affects host physiological homeostasis and behavioral characteristics. Similarly, alterations in gut microbiota could be a feasible strategy for reducing aggressive behavior and improving health in chickens. The study was conducted to determine the effects of early-life cecal microbiota transplantation (CMT) on cecal microbial composition, brain serotonergic activity, and aggressive behavior of recipient chickens.

Chicken lines 6₃ and 7₂ with nonaggressive and aggressive behavior, respectively, were used as donors and a commercial strain Dekalb XL was used as recipients for CMT. Eighty-four 1-d-old male chicks were randomly assigned to 1 of 3 treatments with 7 cages per treatment and 4 chickens per cage (n = 7): saline (control, CTRL), cecal solution of line 6₃ (6₃-CMT), and cecal solution of line 7₂ (7₂-CMT). Transplantation was conducted via oral gavage once daily from d 1 to 10, and then boosted once weekly from week 3 to 5. At weeks 5 and 16, home-cage behavior was recorded, and chickens with similar body weights were assigned to paired aggression tests between the treatments. Samples of blood, brain, and cecal content were collected from the post-tested chickens to detect CMT-induced biological and microbiota changes.

6₃-CMT chickens displayed less aggressive behavior with a higher hypothalamic serotonergic activity at week 5. Correspondingly, two amplicon sequence variants (ASVs) belonging to Lachnospiraceae and one Ruminococcaceae UCG-005 ASV were positively correlated with the levels of brain tryptophan and serotonin, respectively. 7₂-CMT chickens had lower levels of brain norepinephrine and dopamine at week 5 with higher levels of plasma serotonin and tryptophan at week 16. ASVs belonging to Mollicutes RF39 and GCA-900066225 in 7₂-CMT chickens were negatively correlated with the brain 5-hydroxyindoleacetic acid (5-HIAA) at week 5, and one Bacteroides ASV was negatively correlated with plasma serotonin at week 16.

Results indicate that CMT at an early age could regulate aggressive behavior via modulating the cecal microbial composition, together with central serotonergic and catecholaminergic systems in recipient chickens. The selected CMT could be a novel strategy for reducing aggressive behavior through regulating signaling along the microbiota-gut-brain axis.

To investigate anti-aging effects of probiotic-fermented kelp enzymatic hydrolysate culture (KMF), probiotic-fermented kelp enzymatic hydrolysate supernatant (KMFS), and probiotic-fermented kelp enzymatic hydrolysate bacteria suspension (KMFP) in D-galactose-induced aging mice.

The study uses a probiotic-mixture of Lactobacillus reuteri, Pediococcus pentosaceus, and Lactobacillus acidophilus strains for kelp fermentation. KMF, KMFS, and KMFP prevent D-galactose-induced elevation of malondialdehyde levels in serum and brain tissue of aging mice, and they increase superoxide dismutase and catalase levels and total antioxidant capacity. Furthermore, they improve the cell structure of mouse brain, liver, and intestinal tissue. Compared with the model control group, the KMF, KMFS, and KMFP treatments regulate mRNA and protein levels of genes associated with aging, the concentrations of acetic acid, propionic acid, and butyric acid in the three treatment groups are more than 1.4-, 1.3-, and 1.2-fold increased, respectively. Furthermore, the treatments affect the gut microbiota community structures.

These results suggest that KMF, KMFS, and KMFP can modulate gut microbiota imbalances and positively affect aging-related genes to achieve anti-aging effects.

This experiment was designed to evaluate the influences of dietary dandelion polysaccharides (DP) on the performance and cecum microbiota of laying hens. Three hundred laying hens were assigned to five treatment groups: the basal diet group (CK group), three DP groups (basal diets supplemented with 0.5, 1.0, and 1.5 % DP), and the inulin group (IN group, basal diet supplemented with 1.5 % inulin). Increased daily egg weight and a decreased feed conversion rate were observed when the diets were supplemented with inulin or DP. The calcium metabolism rate in the 0.5 % and 1.0 % DP groups was greater than that in the CK group. The DP groups increased the short-chain fatty acid concentration, decreased pH, and enhanced the relative abundances of Parabacteroides, Alloprevotella, and Romboutsia in the cecum. These results showed that DP supplementation in the diets of laying hens can improve their performance, which might be associated with the regulation of the cecal microbiota.

The concept of designer microbiota in chicken is focused on early exposure of the hatchlings to pathogen-free microbiota inoculum, limiting the early access to harmful and pathogenic microorganisms, thus promoting colonisation of the gut with beneficial and natural poultry microbiota. In this study, we controlled colonisation of the intestine in broiler chickens in a large-scale industrial setting via at-hatch administration of a commercial product containing a highly diverse microbiota originating from the chicken caecum. The treatment significantly transformed the microbiota membership in the crop, proventriculus, jejunum and caecum and significantly altered the taxa abundance in the jejunum, jejunum mucosa, and caecum estimated using PERMANOVA and unweighted and weighted UniFrac distances, respectively. The treatment also improved the growth rate in chickens with no significant alteration in feed conversion ratio. A comparison of inoculum product microbiota structure revealed that the inoculum had the highest Shannon diversity index compared to all investigated gut sections, and the number of Observed Species second only to the caecal community. PCoA plots using weighted or unweighted UniFrac placed the inoculum samples together with the samples from the caecal origin.