Integrative mechanisms and intervention targets of the microbiota–gut–brain axis in depressive disorders: advances across immune, endocrine, and central nervous system pathways

Depressive disorders are highly heterogeneous syndromes characterized not only by depressed mood but also by cognitive impairment, sleep–circadian rhythm disturbances, altered appetite, somatic discomfort, and metabolic or gastrointestinal comorbidities. In recent years, the microbiota–gut–brain axis (MGBA) has been increasingly recognized as an integrative biological framework linking abnormalities in mood regulation, immune responses, endocrine function, metabolism, and neuroplasticity. This review provides a systematic synthesis of gut microbial ecology and host phenotypic features associated with depressive disorders, with particular emphasis on the depletion of short-chain fatty acid-producing commensals, the enrichment of potentially pro-inflammatory taxa, and the functional remodeling of key metabolic pathways, including the tryptophan–kynurenine pathway, short-chain fatty acids, bile acids, and trimethylamine N-oxide. We further discuss how bidirectional gut-to-brain and brain-to-gut communication may contribute to the onset and progression of depressive disorders through intestinal barrier disruption, low-grade systemic inflammation, hypothalamic–pituitary–adrenal axis activation, vagal signaling, and dysregulation of neurotransmitter and neurotrophic pathways. Current interventional evidence suggests that dietary and lifestyle modification, psychobiotics, and fecal microbiota transplantation may exert antidepressant potential in selected populations; however, the overall effect sizes remain limited and between-study heterogeneity is substantial. Patients with prominent gastrointestinal symptoms, metabolic abnormalities, or low-grade inflammatory states may represent priority candidates for MGBA-targeted interventions; nevertheless, a putative microbiota-responsive phenotype should not be simply equated with high stress exposure alone, and its definition requires prospective validation integrating stress burden, host responses, and microbial/metabolic readouts. Overall, MGBA research is gradually moving beyond descriptive profiling of microbial composition toward functional integration and clinical translation; however, causal inference, multi-omics standardization, and the identification of stratification biomarkers remain major challenges. Future studies should incorporate phenotype-based stratification, strengthened functional readouts, and precision intervention designs to determine which patients are most likely to benefit from microbiota-targeted therapies.

Comparative effects of structured exercise protocols on depression and anxiety symptoms: a network meta-analysis

ObjectiveTo systematically compare the intervention effects of eight common structured exercise modalities on depressive and anxiety symptoms in adults using a network meta-analysis approach, providing evidence-based insights for developing precision exercise prescriptions in mental health.MethodsA computer search was conducted across PubMed, Web of Science, Embase, and the Cochrane Library databases, covering the period from the database establishment to March 31,2026. Randomized controlled trials comparing different exercise modalities for treating adult depressive or anxiety symptoms were included. Literature quality was assessed using the Cochrane Collaboration’s Bias Risk Assessment Tool (Revised Version), with statistical analyses performed using Stata 19.0 and RevMan 5.4. The standardized mean difference (SMD) was used as the effect measure, consistency was evaluated by the node splitting method, and the cumulative rank-sum area under the curve (SUCRA) was calculated to rank intervention efficacy. Publication bias was assessed and corrected using the trimming method and meta-regression.ResultsA total of 22 studies involving 23 randomized controlled trials with 1,830 participants were included, encompassing eight exercise modalities: yoga, Tai Chi, Pilates, resistance training, aerobic exercise, combined exercise, high-intensity interval training, and moderate-intensity continuous training. Traditional meta-analysis demonstrated that exercise intervention groups showed significantly better improvements in both depressive symptoms (SMD = -0.67,95% CI: -0.97 to-0.37) and anxiety symptoms (SMD = -0.77,95% CI: -1.12 to-0.41) compared to the control groups (both P <0.001). The network meta-analysis results demonstrated that all exercise modalities were effective. In the SUCRA probability ranking, yoga ranked first in both depression (SUCRA = 68.8%) and anxiety (SUCRA = 72.2%) improvement. However, the differences in effect sizes between yoga and moderate-intensity continuous training (MICT) or high-intensity interval training (HIIT) were not statistically significant (all 95% confidence intervals included 0), indicating no clear superiority among the three interventions; thus, this ranking should be regarded as exploratory rather than confirmatory evidence. The top three interventions for depression symptom improvement were yoga, MICT (56.7%), and HIIT (54.6%), while the top three for anxiety symptom improvement were yoga, HIIT (57.4%), and MICT (56.2%). Subgroup analyses revealed no statistically significant moderating effects of intervention duration or age (all P>0.05), although the effect sizes were larger in the elderly group (≥60 years) compared to other age groups. Consistency testing indicated a reliable evidence network (P>0.05). Egger’s test suggested potential publication bias (depression P = 0.017, anxiety P = 0.010), but the meta-analysis did not incorporate missing studies, and meta-regression did not detect small-sample effects; the direction and significance of the effects remained unchanged, rendering the conclusions robust.ConclusionDifferent exercise modalities exhibit beneficial effects on both depression and anxiety symptoms. Yoga, MICT, and HIIT all demonstrated significant potential in alleviating both symptoms; however, the differences in efficacy among the three interventions were not statistically significant, making them all viable prioritized exercise modalities in clinical practice. Clinical selection should be based on a comprehensive evaluation of the patient’s dominant symptom cluster, tolerance, preferences, and safety profile to develop individualized exercise regimens. Since only one study included Pilates, its independent effect remains to be validated.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier.

Social connectedness in mobile gaming: how family dynamics shape children’s virtual interactions

BackgroundMobile gaming is important for children’s social interaction, but its impact on real-life social connectedness depends heavily on family dynamics. How family patterns shape children’s emotional and social experiences around gaming remains underexplored, particularly qualitatively. This study examined how family dynamics influence children’s belonging, emotion regulation, and virtual interactions in mobile gaming.MethodsUsing a phenomenological design, we conducted semi-structured interviews with 20 participants from 10 families across urban, suburban, and rural China. Participants included children (n=10, aged 10-12), parents (n=8, all mothers), and siblings (n=2). All children had played mobile games for ≥6 months. Data were analyzed via thematic analysis (Braun & Clarke). Family patterns were identified based on parental mediation, emotional communication, and children’s sense of connectedness.ResultsThree family patterns emerged. Restrictive-Control Families (4/8) showed high monitoring and low trust, linked to concealment, tension, and social shift to virtual peers. Supportive Co-Play Families (3/8) exhibited shared play, emotional communication, and digital-offline continuity, with children reporting greater resilience and belonging. Sibling-Mediated Families (3 families) featured siblings as companions and emotional buffers, helping manage frustration without direct parental involvement. No severe conflicts or distress were directly caused by gaming in any pattern.ConclusionsChildren’s mobile gaming outcomes are shaped by relational context, not just time. This study identifies three family-level regulatory mechanisms: suppression (restrictive-control), cognitive reappraisal (supportive co-play), and co-regulation (sibling-mediated). These findings extend Social Connectedness Theory, showing how family patterns shape children’s emotion regulation. Supportive co-play and sibling mediation facilitate adaptive regulation and connectedness, while restrictive-control may drive children to virtual spaces. Family-based interventions targeting emotion regulation, not just screen reduction, are recommended. Shifting from “anti-addiction” to “developmental enhancement” offers a safe, practical strategy for integrating gaming into family life.

Why this year’s World Cup ball may not fly as far

Much is new about this month’s upcoming FIFA World Cup tournament, which will be held in the US, Canada, and Mexico. It hosts more teams than ever before. It’s the first to occur in three different host countries. And, like predecessor cups for over half a century, it will employ a soccer ball with a brand-new design.

One group of researchers that has been testing the physics of World Cup balls for the past 20 years recently studied this new entry, called the Trionda. Made by Adidas, the Trionda features four red, green, and blue panels textured with deep grooves and maple leaf, green eagle, and star emblems to represent the three host countries. Through wind-tunnel experiments, the research team found that this ball improves over previous versions in some ways, but long-distance kicks might not go as far as they did in the past. 

“The simple picture is that Trionda may very slightly punish extreme distance, but it should reward clean technique and predictable flight,” says team member John Eric Goff, who researches sports physics and is an incoming professor of engineering practice at Purdue University.  “Goalkeepers, defenders hitting long passes, and long-range shooters are where I would look first for visible differences.” 

Researchers used a wind tunnel to study the Trionda ball at the University of Tsukuba.
TAKESHI ASAI, SUNGCHAN HONG, AND RICHONG LIU

Adidas has been designing new balls for each World Cup since the 1970s. Some of the design changes in the first few decades were aesthetic: The 1986 ball featured graphics inspired by Aztec temples for the Mexico tournament, and 1994’s had space graphics in honor of the moon landing’s 25th anniversary. There were some structural differences too, such as upgraded foam cores and improved water resistance. But by and large, the balls used the same design of 32 pentagonal panels stitched together. 

That changed in the 2006 World Cup in Germany, when Adidas introduced the +Teamgeist ball. It featured just 14 curved panels, which were thermally bonded together rather than stitched. The design helped keep moisture out so the ball wouldn’t grow heavier throughout the game, Goff says. It was around this time that he started studying soccer balls. In the years since then, he and his colleagues have followed the transformations as Adidas has released balls with different surface textures and even fewer panels—design changes significant enough to affect game play. 

In-flight motion

Goff discovered early on that by analyzing a ball’s trajectory data, he could derive its drag coefficient—a number that determines the air resistance it experiences midflight at a given speed. Shortly after, he began working with a team in Japan to analyze how the World Cup ball’s in-flight behavior changes with each new design. 

The experiments, carried out at the University of Tsukuba in Japan, have been purposely consistent over the years because “maintaining continuity is important for comparing new data with historical data sets,” says Takeshi Asai, a professor there who works on the experiments. They entail attaching the ball to a metal rod connected to an instrument called a force balance, which measures aerodynamic forces such as drag and lift as the ball is exposed to the same wind speeds it would experience in a real soccer game—seven to 35 meters per second. 

The team tests the ball in different orientations, “but you can only do a few because the Trionda ball is $170,” Goff says, and each new test effectively destroys it. The experiments show the team how the drag coefficient changes with speed, and Goff then writes code to simulate the ball’s overall trajectory as it flies through the air.  

The team’s analysis has shown how recent World Cup balls evolved since the eight-panel Jabulani ball for the 2010 event. The Jabulani faced much criticism from players—particularly goalkeepers, who said it had a deceptive trajectory that “dipped wickedly,” as one player told the Guardian

Adidas JABULANI, official ball of the FIFA World Cup 2010

ALAMY
Adidas Brazuca Match ball for the 2014 World Cup

ADOBE STOCK
Trionda official 2026 FIFA match ball

TAKESHI ASAI, SUNGCHAN HONG, RICHONG LIU

The 2010 Jabulani ball (left) had eight panels and a smooth texture that translated into unpredictable performance. Later balls, like the 2014 Brazuca (center) and this year’s Trionda (right) have fewer panels but more roughness.

The ball had one key flaw: It was too smooth. Even though its drag coefficient was relatively low at high speeds, once the ball slowed to a certain point the coefficient would ratchet up, causing it to lose speed quite fast and behave as the 2010 players complained. This sudden transition—called the drag crisis—occurs at higher speeds for smoother balls, but with added texture like seams and grooves, the transition can be avoided until a ball reaches lower speeds. This allows the ball to travel farther and generally behave in a more predictable way during typical play. 

“It’s the same reason why golf balls have dimples and baseballs have those nice 108 double stitches. If those rough features of those balls were not there, you would not get anywhere near the kind of distance when those balls are thrown or hit that you see now,” Goff says. “There has to be some kind of a roughness on the ball to move this transition to a smaller speed.”

New grooves

Subsequent designs have been able to push the drag crisis to lower speeds, according to the analysis by Goff and his colleagues. The Brazuca ball used in 2014, for instance, has only six panels, but their total seam length is much longer, adding to the surface’s roughness. And this year’s Trionda ball contains just four panels, but each panel also has three deep grooves for more texture. 

There’s a trade-off to this roughness, though. While Goff and his colleagues found that the Trionda ball experiences the drag crisis at the slowest speed since 2010, its drag coefficient is also higher than that of the other balls at high speeds. That means that even though the most dramatic change doesn’t happen until the ball is moving quite slowly, the ball will still slow down faster than its recent predecessors during the faster portion of its flight. So the trajectories of long kicks may be a few meters shorter, Goff says. Adidas did not respond to a request for comment.

Fortunately, players in the upcoming World Cup should already be familiar with these added nuances, as they’ve had access to the new ball for at least a few months. The ball, Goff notes, is quite similar to Nike’s Flight ball in design, so players who’ve spent more time with that ball may have an added advantage. 

Meanwhile, Goff continues sending the group’s papers to his colleagues FIFA and Adidas in hope of providing some new insights, and he’s been sent balls by Adidas in the past. Adidas does perform its own unpublished tests of each new ball. The New York Times reported last year that the Trionda’s 3.5-year testing process included robotics designed to kick the ball at specific speeds as well as testing in seven of the 16 host locations. 

But as Goff sees it, soccer is “the world’s most popular sport, [this is] its most important tournament, and the most important piece of equipment in that tournament is this ball right here,” indicating the the Trionda ball that he had on camera with him during our Zoom call. “I think they’re interested in what some external testing looks like.”

Opinion: American horses are obese, too

The horses in America are getting fat. They are trying to tell us something.

Fifty-one percent of mature light-breed horses in the United States are obese — a rate that ranks among the world’s highest, slightly above Britain and nearly twice that of Australia or Denmark. That figure comes from a peer-reviewed prevalence study, and it sits alongside a number that should give any clinician pause: The U.S. also leads the G7 in human obesity. The same country. The same epidemic. A completely different species.

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