Macaques Research Articles

Nonuniform and pathway-specific laminar processing of spatial frequencies in the primary visual cortex of primates

The neocortex comprises six cortical layers that play a crucial role in information processing; however, it remains unclear whether laminar processing is consistent across all regions within a single cortex. In this study, we demonstrate diverse laminar response patterns in the primary visual cortex (V1) of three male macaque monkeys when exposed to visual stimuli at different spatial frequencies (SFs). These response patterns can be categorized into two groups. One group exhibit suppressed responses in the output layers for all SFs, while the other type shows amplified responses specifically at high SFs. Further analysis suggests that both magnocellular (M) and parvocellular (P) pathways contribute to the suppressive effect through feedforward mechanisms, whereas amplification is specific to local recurrent mechanisms within the parvocellular pathway. These findings highlight the non-uniform distribution of neural mechanisms involved in laminar processing and emphasize how pathway-specific amplification selectively enhances representations of high-SF information in primate V1.

Real-time fluorescence loop-mediated isothermal amplification assays for detection of zoonotic malaria Plasmodium parasites

BackgroundNatural human infections by Plasmodium cynomolgi and P. inui have been reported recently and gain the substantial attention from Southeast Asian countries. Zoonotic transmission of non-human malaria parasites to humans from macaque monkeys occurred through the bites of the infected mosquitoes. The objective of this study is to establish real-time fluorescence loop-mediated isothermal amplification (LAMP) assays for the detection of zoonotic malaria parasites by combining real-time fluorescent technology with the isothermal amplification technique. MethodsBy using 18S rRNA as the target gene, the primers for P. cynomolgi, P. coatneyi and P. inui were newly designed in the present study. Four novel real-time fluorescence LAMP assays were developed for the detection of P. cynomolgi, P. coatneyi, P. inui and P. knowlesi. The entire amplification process was completed in 60 min, with the assays performed at 65 °C. By using SYTO-9 as the nucleic acid intercalating dye, the reaction was monitored via real-time fluorescence signal. ResultsThere was no observed cross-reactivity among the primers from different species. All 70 field-collected monkey samples were successfully amplified by real-time fluorescence LAMP assays. The detection limit for P. cynomolgi, P. coatneyi and P. knowlesi was 5 × 109 copies/µL. Meanwhile, the detection limit of P. inui was 5 × 1010 copies/µL. ConclusionThis is the first report of the detection of four zoonotic malaria parasites by real-time fluorescence LAMP approaches. It is an effective, rapid and simple-to-use technique. This presented platform exhibits considerable potential as an alternative detection for zoonotic malaria parasites.

Helicobacter pylori infection in infant rhesus macaque monkeys is associated with an altered lung and oral microbiome

It is estimated that more than half of the world population has been infected with Helicobacter pylori. Most newly acquired H. pylori infections occur in children before 10 years of age. We hypothesized that early life H. pylori infection could influence the composition of the microbiome at mucosal sites distant to the stomach. To test this hypothesis, we utilized the infant rhesus macaque monkey as an animal model of natural H. pylori colonization to determine the impact of infection on the lung and oral microbiome during a window of postnatal development. From a cohort of 4–7 month-old monkeys, gastric biopsy cultures identified 44% of animals infected by H. pylori. 16S ribosomal RNA gene sequencing of lung washes and buccal swabs from animals showed distinct profiles for the lung and oral microbiome, independent of H. pylori infection. In order of relative abundance, the lung microbiome was dominated by the phyla Proteobacteria, Firmicutes, Bacteroidota, Fusobacteriota, Campilobacterota and Actinobacteriota while the oral microbiome was dominated by Proteobacteria, Firmicutes, Bacteroidota, and Fusobacteriota. In comparison to the oral cavity, the lung was composed of more genera and species that significantly differed by H. pylori status, with a total of 6 genera and species that were increased in H. pylori negative infant monkey lungs. Lung, but not plasma IL-8 concentration was also associated with gastric H. pylori load and lung microbial composition. We found the infant rhesus macaque monkey lung harbors a microbiome signature that is distinct from that of the oral cavity during postnatal development. Gastric H. pylori colonization and IL-8 protein were linked to the composition of microbial communities in the lung and oral cavity. Collectively, these findings provide insight into how H. pylori infection might contribute to the gut-lung axis during early childhood and modulate future respiratory health.

Abstract deliberation by visuomotor neurons in prefrontal cortex

During visually guided behavior, the prefrontal cortex plays a pivotal role in mapping sensory inputs onto appropriate motor plans. When the sensory input is ambiguous, this involves deliberation. It is not known whether the deliberation is implemented as a competition between possible stimulus interpretations or between possible motor plans. Here we study neural population activity in the prefrontal cortex of macaque monkeys trained to flexibly report perceptual judgments of ambiguous visual stimuli. We find that the population activity initially represents the formation of a perceptual choice before transitioning into the representation of the motor plan. Stimulus strength and prior expectations both bear on the formation of the perceptual choice, but not on the formation of the action plan. These results suggest that prefrontal circuits involved in action selection are also used for the deliberation of abstract propositions divorced from a specific motor plan, thus providing a crucial mechanism for abstract reasoning.

Visual Preference for Socially Relevant Spatial Relations in Humans and Monkeys.

As a powerful social signal, a body, face, or gaze facing toward oneself holds an individual's attention. We asked whether, going beyond an egocentric stance, facingness between others has a similar effect and why. In a preferential-looking time paradigm, human adults showed spontaneous preference to look at two bodies facing toward (vs. away from) each other (Experiment 1a, N = 24). Moreover, facing dyads were rated higher on social semantic dimensions, showing that facingness adds social value to stimuli (Experiment 1b, N = 138). The same visual preference was found in juvenile macaque monkeys (Experiment 2, N = 21). Finally, on the human development timescale, this preference emerged by 5 years, although young infants by 7 months of age already discriminate visual scenes on the basis of body positioning (Experiment 3, N = 120). We discuss how the preference for facing dyads-shared by human adults, young children, and macaques-can signal a new milestone in social cognition development, supporting processing and learning from third-party social interactions.

Secondary somatosensory and posterior insular cortices: a somatomotor hub for object prehension and manipulation movements.

The secondary somatosensory cortex (SII) and posterior insular cortex (pIC) are recognized for processing touch and movement information during hand manipulation in humans and non-human primates. However, their involvement in three-dimensional (3D) object manipulation remains unclear. To investigate neural activity related to hand manipulation in the SII/pIC, we trained two macaque monkeys to grasp three objects (a cone, a plate, and a ring) and engage in visual fixation on the object. Our results revealed that 19.4% (n = 50/257) of the task-related neurons in SII/pIC were active during hand manipulations, but did not respond to passive somatosensory stimuli. Among these neurons, 44% fired before hand-object contact (reaching to grasping neurons), 30% maintained tonic activity after contact (holding neurons), and 26% showed continuous discharge before and after contact (non-selective neurons). Object grasping-selectivity varied and was weak among these neurons, with only 24% responding to fixation of a 3D object (visuo-motor neurons). Even neurons unresponsive to passive visual stimuli showed responses to set-related activity before the onset of movement (42%, n = 21/50). Our findings suggest that somatomotor integration within SII/pIC is probably integral to all prehension sequences, including reaching, grasping, and object manipulation movements. Moreover, the existence of a set-related activity within SII/pIC may play a role in directing somatomotor attention during object prehension-manipulation in the absence of vision. Overall, SII/pIC may play a role as a somatomotor hub within the lateral grasping network that supports the generation of intentional hand actions based on haptic information.

Acute Neuropixels Recordings in the Marmoset Monkey.

High-density linear probes, such as Neuropixels, provide an unprecedented opportunity to understand how neural populations within specific laminar compartments contribute to behavior. Marmoset monkeys, unlike macaque monkeys, have a lissencephalic (smooth) cortex that enables recording perpendicular to the cortical surface, thus making them an ideal animal model for studying laminar computations. Here we present a method for acute Neuropixels recordings in the common marmoset (Callithrix jacchus). The approach replaces the native dura with an artificial silicon-based dura that grants visual access to the cortical surface, which is helpful in avoiding blood vessels, ensures perpendicular penetrations, and could be used in conjunction with optical imaging or optogenetic techniques. The chamber housing the artificial dura is simple to maintain with minimal risk of infection and could be combined with semichronic microdrives and wireless recording hardware. This technique enables repeated acute penetrations over a period of several months. With occasional removal of tissue growth on the pial surface, recordings can be performed for a year or more. The approach is fully compatible with Neuropixels probes, enabling the recording of hundreds of single neurons distributed throughout the cortical column.

Evolutionarily conserved neural responses to affective touch in monkeys transcend consciousness and change with age

Affective touch-a slow, gentle, and pleasant form of touch-activates a different neural network than which is activated during discriminative touch in humans. Affective touch perception is enabled by specialized low-threshold mechanoreceptors in the skin with unmyelinated fibers called C tactile (CT) afferents. These CT afferents are conserved across mammalian species, including macaque monkeys. However, it is unknown whether the neural representation of affective touch is the same across species and whether affective touch's capacity to activate the hubs of the brain that compute socioaffective information requires conscious perception. Here, we used functional MRI to assess the preferential activation of neural hubs by slow (affective) vs. fast (discriminative) touch in anesthetized rhesus monkeys (Macaca mulatta). The insula, anterior cingulate cortex (ACC), amygdala, and secondary somatosensory cortex were all significantly more active during slow touch relative to fast touch, suggesting homologous activation of the interoceptive-allostatic network across primate species during affective touch. Further, we found that neural responses to affective vs. discriminative touch in the insula and ACC (the primary cortical hubs for interoceptive processing) changed significantly with age. Insula and ACC in younger animals differentiated between slow and fast touch, while activity was comparable between conditions for aged monkeys (equivalent to >70 y in humans). These results, together with prior studies establishing conserved peripheral nervous system mechanisms of affective touch transduction, suggest that neural responses to affective touch are evolutionarily conserved in monkeys, significantly impacted in old age, and do not necessitate conscious experience of touch.

Genomic Evidence for the Complex Evolutionary History of Macaques (Genus Macaca).

The genus Macaca is widely distributed, occupies a variety of habitats, shows diverse phenotypic characteristics, and is one of the best-studied genera of nonhuman primates. Here, we reported five re-sequencing Macaca genomes, including one M. cyclopis, one M. fuscata, one M. thibetana, one M. silenus, and one M. sylvanus. Together with published genomes of other macaque species, we combined 20 genome sequences of 10 macaque species to investigate the gene introgression and genetic differences among the species. The network analysis of the SNV-fragment trees indicates a reticular phylogeny of macaque species. Combining the results from various analytical methods, we identified extensive ancient introgression events among macaque species. The multiple introgression signals between different species groups were also observed, such as between fascicularis group species and silenus group species. However, gene flow signals between fascicularis and sinica group were not as strong as those between fascicularis group and silenus group. On the other hand, the unidirect gene flow in M. arctoides probably occurred between the progenitor of M. arctoides and the common ancestor of fascicularis group. Our study also shows that the genetic backgrounds and genetic diversity of different macaques vary dramatically among species, even among populations of the same species. In conclusion, using whole genome sequences and multiple methods, we have studied the evolutionary history of the genus Macaca and provided evidence for extensive introgression among the species.

Perceptography unveils the causal contribution of inferior temporal cortex to visual perception

Neurons in the inferotemporal (IT) cortex respond selectively to complex visual features, implying their role in object perception. However, perception is subjective and cannot be read out from neural responses; thus, bridging the causal gap between neural activity and perception demands independent characterization of perception. Historically, though, the complexity of the perceptual alterations induced by artificial stimulation of IT cortex has rendered them impossible to quantify. To address this old problem, we tasked male macaque monkeys to detect and report optical impulses delivered to their IT cortex. Combining machine learning with high-throughput behavioral optogenetics, we generated complex and highly specific images that were hard for the animal to distinguish from the state of being cortically stimulated. These images, named “perceptograms” for the first time, reveal and depict the contents of the complex hallucinatory percepts induced by local neural perturbation in IT cortex. Furthermore, we found that the nature and magnitude of these hallucinations highly depend on concurrent visual input, stimulation location, and intensity. Objective characterization of stimulation-induced perceptual events opens the door to developing a mechanistic theory of visual perception. Further, it enables us to make better visual prosthetic devices and gain a greater understanding of visual hallucinations in mental disorders.

Neural correlates of perceptual similarity masking in primate V1.

Visual detection is a fundamental natural task. Detection becomes more challenging as the similarity between the target and the background in which it is embedded increases, a phenomenon termed 'similarity masking'. To test the hypothesis that V1 contributes to similarity masking, we used voltage sensitive dye imaging (VSDI) to measure V1 population responses while macaque monkeys performed a detection task under varying levels of target-background similarity. Paradoxically, we find that during an initial transient phase, V1 responses to the target are enhanced, rather than suppressed, by target-background similarity. This effect reverses in the second phase of the response, so that in this phase V1 signals are positively correlated with the behavioral effect of similarity. Finally, we show that a simple model with delayed divisive normalization can qualitatively account for our findings. Overall, our results support the hypothesis that a nonlinear gain control mechanism in V1 contributes to perceptual similarity masking.

Neural correlates of perceptual similarity masking in primate V1

Visual detection is a fundamental natural task. Detection becomes more challenging as the similarity between the target and the background in which it is embedded increases, a phenomenon termed ‘similarity masking’. To test the hypothesis that V1 contributes to similarity masking, we used voltage sensitive dye imaging (VSDI) to measure V1 population responses while macaque monkeys performed a detection task under varying levels of target-background similarity. Paradoxically, we find that during an initial transient phase, V1 responses to the target are enhanced, rather than suppressed, by target-background similarity. This effect reverses in the second phase of the response, so that in this phase V1 signals are positively correlated with the behavioral effect of similarity. Finally, we show that a simple model with delayed divisive normalization can qualitatively account for our findings. Overall, our results support the hypothesis that a nonlinear gain control mechanism in V1 contributes to perceptual similarity masking.

Differential Modulation of Local Field Potentials in the Primary and Premotor Cortices during Ipsilateral and Contralateral Reach to Grasp in Macaque Monkeys.

Hand movements are associated with modulations of neuronal activity across several interconnected cortical areas, including the primary motor cortex (M1) and the dorsal and ventral premotor cortices (PMd and PMv). Local field potentials (LFPs) provide a link between neuronal discharges and synaptic inputs. Our current understanding of how LFPs vary in M1, PMd, and PMv during contralateral and ipsilateral movements is incomplete. To help reveal unique features in the pattern of modulations, we simultaneously recorded LFPs in these areas in two macaque monkeys performing reach and grasp movements with either the right or left hand. The greatest effector-dependent differences were seen in M1, at low (≤13 Hz) and γ frequencies. In premotor areas, differences related to hand use were only present in low frequencies. PMv exhibited the greatest increase in low frequencies during instruction cues and the smallest effector-dependent modulation during movement execution. In PMd, δ oscillations were greater during contralateral reach and grasp, and β activity increased during contralateral grasp. In contrast, β oscillations decreased in M1 and PMv. These results suggest that while M1 primarily exhibits effector-specific LFP activity, premotor areas compute more effector-independent aspects of the task requirements, particularly during movement preparation for PMv and production for PMd. The generation of precise hand movements likely relies on the combination of complementary information contained in the unique pattern of neural modulations contained in each cortical area. Accordingly, integrating LFPs from premotor areas and M1 could enhance the performance and robustness of brain-machine interfaces.

Differential clustering of visual and choice- and saccade-related activity in macaque V3A and CIP.

Neurons in sensory and motor cortices tend to aggregate in clusters with similar functional properties. Within the primate dorsal ("where") pathway, an important interface between three-dimensional (3-D) visual processing and motor-related functions consists of two hierarchically organized areas: V3A and the caudal intraparietal (CIP) area. In these areas, 3-D visual information, choice-related activity, and saccade-related activity converge, often at the single-neuron level. Characterizing the clustering of functional properties in areas with mixed selectivity, such as these, may help reveal organizational principles that support sensorimotor transformations. Here we quantified the clustering of visual feature selectivity, choice-related activity, and saccade-related activity by performing correlational and parametric comparisons of the responses of well-isolated, simultaneously recorded neurons in macaque monkeys. Each functional domain showed statistically significant clustering in both areas. However, there were also domain-specific differences in the strength of clustering across the areas. Visual feature selectivity and saccade-related activity were more strongly clustered in V3A than in CIP. In contrast, choice-related activity was more strongly clustered in CIP than in V3A. These differences in clustering may reflect the areas' roles in sensorimotor processing. Stronger clustering of visual and saccade-related activity in V3A may reflect a greater role in within-domain processing, as opposed to cross-domain synthesis. In contrast, stronger clustering of choice-related activity in CIP may reflect a greater role in synthesizing information across functional domains to bridge perception and action.NEW & NOTEWORTHY The occipital and parietal cortices of macaque monkeys are bridged by hierarchically organized areas V3A and CIP. These areas support 3-D visual transformations, carry choice-related activity during 3-D perceptual tasks, and possess saccade-related activity. This study quantifies the functional clustering of neuronal response properties within V3A and CIP for each of these domains. The findings reveal domain-specific cross-area differences in clustering that may reflect the areas' roles in sensorimotor processing.

Specific Real-Time PCR Assay Targeting D-loop Gene and Short Amplicon Sequencing for Identification of Monkey Meat in Beef Meatballs

Macaque monkey (Macaca fascicularis) meat (MM) has been reported to be consumed as meatball and soup products in Indonesia. MM is not allowed to be traded in Indonesia and is considered not halal meat; therefore, MM is not allowed to be consumed by Muslim communities. In this study, species-specific primer (SSP) targeting on mitochondrial displacement (D-loop) region coupled with real-time PCR assay was used to identify monkey meat in beef meatballs. The PCR product was also subjected to sequencing in order to ensure the adulteration practice of MM in beef meatballs. The primers were designed and subjected to in silico specificity test using BLAST. The used primers were: forward: 5’-TGACTCCCACCACATCCC-3’ and reverse: 5’-GTGTGGAGCTAGAATATTGAACCG-3’. Real-time PCR assay using SSP targeting on mt-D-loop primers was capable of identifying MM in meatball products, specifically with a detection limit of 0.0078 ng corresponding to 1% MM in beef meatballs. The developed method can be proposed as the standard method for detecting MM in food products intended for halal authentication analysis, provided that DNAs are available in food products.

Characterization of Neural Plasticity in Monkey Models of Neuropathic Pain – A Secondary Publication

Neuropathic pain can occur as a result of injuries and diseases of the nervous system. Animal models using rodents have been developed and characterized to reveal plastic changes underlying neuropathic pain. However, structures and functions of some brain areas that are associated with pain perception differ between rodents and primates. Therefore, animal models using non-human primates, such as the macaque monkey, with brain structures and functions closer to those of humans are important for elucidating the mechanisms underlying pain in human patients. Recently, we measured brain activity using functional magnetic resonance imaging (fMRI) in a macaque model of chemotherapy-induced neuropathic pain and reported abnormal activation of pain-related brain regions including insular and secondary somatosensory cortices. In the monkey model of central post-stroke pain, moreover, the increased activation of pain-related areas as seen in the patients was confirmed by fMRI. These results indicate that fMRI measurement of brain activity combined with behavioral outcomes in macaque models could be used not only to understand the pathogenetic mechanisms but also to test therapeutic interventions for neuropathic pain.

Quantity, distribution and phenotype of newly generated cells in the intact spinal cord of adult macaque monkeys

The existence of proliferating cells in the intact spinal cord, their distribution and phenotype, are well studied in rodents. A limited number of studies also address the proliferation after spinal cord injury, in non-human primates. However, a detailed description of the quantity, distribution and phenotype of proliferating cells at different anatomical levels of the intact adult non-human primate spinal cord is lacking at present. In the present study, we analyzed normal spinal cord tissues from adult macaque monkeys (Macaca fuscata), infused with Bromo-2′-deoxyuridine (BrdU), and euthanized at 2h, 2 weeks, 5 weeks and 10 weeks after BrdU. We found a significantly higher density of BrdU + cells in the gray matter of cervical segments as compared to thoracic or lumbar segments, and a significantly higher density of proliferating cells in the posterior as compared to the anterior horn of the gray matter. BrdU + cells exhibited phenotype of microglia or endothelial cells (∼50%) or astroglial and oligodendroglial cells (∼40%), including glial progenitor phenotypes marked by the transcription factors Sox9 and Sox10. BrdU + cells also co-expressed other transcription factors known for their involvement in embryonic development, including Emx2, Sox1, Sox2, Ngn1, Olig1, Olig2, Olig3. In the central canal, BrdU + cells were located along the dorso-ventral axis and co-labeled for the markers Vimentin and Nestin. These results reveal the extent of cellular plasticity in the spinal cord of non-human primates under normal conditions.

Pathways from the superior colliculus and the nucleus of the optic tract to the posterior parietal cortex in macaque monkeys: Functional frameworks for representation updating and online movement guidance.

The posterior parietal cortex (PPC) integrates multisensory and motor-related information for generating and updating body representations and movement plans. We used retrograde transneuronal transfer of rabies virus combined with a conventional tracer in macaque monkeys to identify direct and disynaptic pathways to the arm-related rostral medial intraparietal area (MIP), the ventral lateral intraparietal area (LIPv), belonging to the parietal eye field, and the pursuit-related lateral subdivision of the medial superior temporal area (MSTl). We found that these areas receive major disynaptic pathways via the thalamus from the nucleus of the optic tract (NOT) and the superior colliculus (SC), mainly ipsilaterally. NOT pathways, targeting MSTl most prominently, serve to process the sensory consequences of slow eye movements for which the NOT is the key sensorimotor interface. They potentially contribute to the directional asymmetry of the pursuit and optokinetic systems. MSTl and LIPv receive feedforward inputs from SC visual layers, which are potential correlates for fast detection of motion, perceptual saccadic suppression and visual spatial attention. MSTl is the target of efference copy pathways from saccade- and head-related compartments of SC motor layers and head-related reticulospinal neurons. They are potential sources of extraretinal signals related to eye and head movement in MSTl visual-tracking neurons. LIPv and rostral MIP receive efference copy pathways from all SC motor layers, providing online estimates of eye, head and arm movements. Our findings have important implications for understanding the role of the PPC in representation updating, internal models for online movement guidance, eye-hand coordination and optic ataxia.

Mesenchymal stem cells reverse thymus aging by reprogramming the DNA methylation of thymic epithelial cells

BackgroundA decrease in the number and activity of thymic epithelial cells (TECs) is an important factor in thymic degeneration. Mesenchymal stem cells (MSCs) treating thymic ageing is a promising strategy, but the DNA methylation modification mechanism in TECs remains unclear. MethodsAged rhesus monkeys were treated with MSCs to establish a thymic senescence model, and hematoxylin-eosin (HE) staining, immunofluorescence staining, and ELISA were performed to observe the structure and function of the thymus. TEC aging model and MSCs co-culture system were established to detect DNA methylation modification and transcriptomic changes, correlation analysis between transcription factor methylation and mRNA expression, and q-PCR, immunofluorescence staining, and Western blot were used to identified key genes. ResultsMSCs improved the structure and function of thymus in elderly macaque monkeys; reduced the expression levels of β-Gal, P16, and P21; and increased the activity of aging TECs. There were 501 genes with increased methylation in the promoter region in the treated group compared with the untreated group, among which 23 genes were involved in the negative regulation of cell growth, proliferation and apoptosis, while 591 genes had decreased methylation, among which 37 genes were associated with promoting cell growth and proliferation and inhibiting apoptosis. Furthermore, 66 genes showed a negative correlation between promoter methylation levels and gene transcription; specifically, PDE5A, DUOX2, LAMP1 and SVIL were downregulated with increased methylation, inhibiting growth and development, while POLR3G, PGF, CHTF18, KRT17, FOXJ1, NGF, DYRK3, LRP8, CDT1, PRELID1, F2R, KNTC1 and TRIM3 were upregulated with decreased methylation, promoting cell growth. ConclusionMSCs improve the structure and function of aged thymus, which involves the regulation of DNA methylation profiles and a decrease in the methylation level of the transcription factor NGF to specifically upregulate KRT17 and FOXJ1 to promote the proliferation of TECs.

Mixed probiotics reduce the severity of stress-induced depressive-like behaviors

In recent years, the gut microbiome has gained significant attention in the spheres of research and public health. As a result, studies have increasingly explored the potential of probiotic dietary supplements as treatment interventions for conditions such as anxiety and depression. The present study examined the effect of mixed probiotics (Lacticaseibacillus rhamnosus and Enterococcus faecium) on inflammation, microbiome composition, and depressive-like behaviors in a macaque monkey model. The mixed probiotics effectively reduced the severity of depressive-like behaviors in macaque monkeys. Further, treatment with mixed probiotics gradually increased the abundance of beneficial bacteria in the gut, improving the balance of the gut microbiota. Additionally, macaques treated with the mixed probiotics showed decreased serum levels of inflammatory factors (P < 0.05), an increased rate of L-tryptophan metabolism (P < 0.05), and the restoration of 5-HT and 5-HTP levels (P < 0.05). Correlation analysis confirmed that Lacticaseibacillus and other beneficial bacteria exhibited a negative correlation with inflammation in the body (P < 0.05), and a positive correlation with tryptophan metabolism (P < 0.05). In conclusion, the mixed probiotics effectively restored intestinal homeostasis in macaques and enhanced tryptophan metabolism, ultimately alleviating inflammation and depressive-like behaviors.