Probiotics vs SSRIs for Mild Anxiety -2025 Meta-Analysis A Comprehensive Guide

Introduction: Probiotics vs SSRIs for Mild Anxiety

In recent years, the landscape of anxiety treatment has undergone significant evolution, with growing interest in alternative approaches beyond traditional pharmacotherapy. As we navigate through 2025, one of the most compelling developments has been the emergence of probiotics as a potential intervention for anxiety disorders, challenging the long-standing dominance of selective serotonin reuptake inhibitors (SSRIs) as the first-line treatment.

This comprehensive guide examines the latest meta-analytical evidence comparing probiotics and SSRIs for mild anxiety, providing healthcare professionals, researchers, and patients with an in-depth understanding of efficacy, mechanisms of action, side effect profiles, and practical implementation strategies for both treatment approaches.

Understanding Anxiety Disorders in 2025

Anxiety disorders remain among the most prevalent mental health conditions worldwide, affecting approximately 275 million people globally. These disorders are characterized by excessive worry, fear, and related behavioral disturbances that can significantly impair daily functioning and quality of life.

The Spectrum of Anxiety Disorders

Anxiety presents along a spectrum of severity, from mild to severe, with corresponding variations in treatment approaches:

• Mild anxiety: Characterized by worry and nervousness that causes some distress but minimal functional impairment
• Moderate anxiety: More persistent symptoms with noticeable impact on daily functioning
• Severe anxiety: Intense symptoms causing significant distress and substantial functional impairment

This guide focuses specifically on mild anxiety, where the risk-benefit analysis of treatment options becomes particularly nuanced, and where non-pharmacological or alternative approaches may offer comparable benefits with potentially fewer adverse effects.

The Evolving Treatment Landscape

Traditionally, the treatment of anxiety disorders has relied on a combination of psychotherapy (particularly cognitive-behavioral therapy) and pharmacotherapy. Among pharmacological options, SSRIs have long been considered the first-line treatment due to their established efficacy and relatively favorable side effect profile compared to older medications.

However, the past decade has witnessed growing interest in the gut-brain axis and the potential role of the gut microbiome in mental health. This has led to increased research into probiotics as a potential intervention for anxiety and other mental health conditions, culminating in several high-quality randomized controlled trials (RCTs) and meta-analyses by 2025.

The Gut-Brain Axis: Foundation for Probiotic Interventions

The gut-brain axis represents the bidirectional communication network between the central nervous system and the enteric nervous system, involving neural, immune, endocrine, and metabolic pathways. This complex system provides the theoretical foundation for how probiotics might influence mental health.

Key Components of the Gut-Brain Connection

1. Vagus Nerve Signaling: Direct neural communication between gut and brain
2. Immune System Mediation: Gut microbiota influence systemic inflammation, which affects brain function
3. Neurotransmitter Production: Gut bacteria produce or influence the production of neurotransmitters including serotonin, GABA, and dopamine
4. Hypothalamic-Pituitary-Adrenal (HPA) Axis: Gut microbiota influence stress response systems
5. Microbial Metabolites: Bacterial byproducts like short-chain fatty acids affect brain function and neuroinflammation

Dysbiosis and Anxiety

Research has increasingly demonstrated associations between gut microbiome composition and anxiety symptoms. A 2025 narrative review highlighted that individuals with anxiety disorders often exhibit gut microbiota alterations, including:

• Reduced microbial diversity
• Lower abundance of short-chain fatty acid-producing bacteria
• Increased levels of potentially harmful bacteria like Escherichia-Shigella

These findings suggest that interventions targeting the gut microbiome, such as probiotics, may have therapeutic potential for anxiety disorders.

SSRIs: The Traditional First-Line Treatment

Selective serotonin reuptake inhibitors (SSRIs) have been the mainstay of anxiety treatment since the late 1990s. Understanding their mechanisms, efficacy, and limitations provides essential context for comparing them with probiotic interventions.

Mechanism of Action

SSRIs work primarily by inhibiting the reuptake of serotonin (5-hydroxytryptamine or 5-HT) in the brain, increasing the availability of this neurotransmitter in the synaptic cleft. This leads to enhanced serotonergic neurotransmission, which is believed to mediate the therapeutic effects on anxiety and mood.

Key SSRIs used for anxiety disorders include:

• Escitalopram (Lexapro)
• Sertraline (Zoloft)
• Paroxetine (Paxil)
• Fluoxetine (Prozac)
• Citalopram (Celexa)
• Fluvoxamine (Luvox)

Efficacy for Mild Anxiety

The efficacy of SSRIs for anxiety disorders is well-established through numerous clinical trials and meta-analyses. However, their effectiveness specifically for mild anxiety has been questioned in recent years.

A 2022 meta-analysis found that while SSRIs are clearly effective for moderate to severe anxiety, their benefits for mild anxiety are more modest, with standardized mean differences (SMDs) ranging from -0.16 to -0.81 compared to placebo, depending on the specific medication.

Side Effect Profile

While generally considered safer than older anxiolytic medications, SSRIs are associated with a range of side effects that can impact treatment adherence and quality of life:

Common Side Effects:

• Nausea and gastrointestinal disturbances
• Sexual dysfunction (reduced libido, delayed orgasm)
• Sleep disturbances
• Headache
• Increased anxiety or jitteriness (especially during initiation)
• Weight changes

Less Common but Serious Side Effects:

• Increased suicidal thoughts (particularly in young adults)
• Serotonin syndrome (when combined with other serotonergic medications)
• Withdrawal symptoms upon discontinuation
• Bleeding risk (especially when combined with NSAIDs or anticoagulants)

The side effect profile of SSRIs has been a significant driver in the search for alternative treatments, particularly for individuals with milder forms of anxiety where the risk-benefit ratio may be less favorable.

Probiotics: The Emerging Alternative

Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. While traditionally associated with digestive health, their potential applications have expanded to include mental health conditions like anxiety.

Mechanism of Action for Anxiety Reduction

Probiotics may influence anxiety through several mechanisms:

1. Modulation of neurotransmitter production: Certain probiotic strains can produce or influence the production of neurotransmitters like GABA, serotonin, and dopamine
2. Reduction of inflammation: Probiotics can reduce systemic inflammation, which has been linked to anxiety and other mental health conditions
3. HPA axis regulation: Probiotics may help normalize stress response by modulating the hypothalamic-pituitary-adrenal axis
4. Vagus nerve signaling: Certain probiotic strains can activate vagal pathways, influencing brain function and behavior
5. Intestinal barrier improvement: By enhancing gut barrier function, probiotics may reduce “leaky gut” and associated inflammatory responses that can affect brain function

Key Probiotic Strains for Anxiety

Research has identified several probiotic strains with potential anxiolytic effects:

Multi-strain formulations have generally shown stronger effects than single-strain products, suggesting synergistic benefits from diverse probiotic species.

Side Effect Profile

One of the most compelling aspects of probiotics is their favorable safety profile:

Common Side Effects:

• Temporary digestive discomfort (gas, bloating)
• Mild abdominal pain
• Changes in bowel habits

Rare Side Effects:

• Infection risk in severely immunocompromised individuals
• Allergic reactions
• Headache

The generally benign side effect profile of probiotics makes them an attractive option for individuals with mild anxiety, where the risk-benefit calculation of more potent medications may be less favorable.

2025 Meta-Analysis: Probiotics vs. SSRIs for Mild Anxiety

The most comprehensive evidence comparing probiotics and SSRIs comes from a landmark 2025 meta-analysis published in the journal Cell Host & Microbe, which synthesized data from 54 randomized controlled trials involving 4,295 participants with mild to moderate anxiety.

Key Findings

1. Overall Efficacy:
   • Probiotics significantly reduced anxiety compared to placebo (Standardized Mean Difference [SMD] = 0.29, p = 0.0139)
   • SSRIs showed slightly stronger effects (SMD ranging from 0.16 to 0.81, depending on the specific medication)
   • For mild anxiety specifically, the efficacy gap narrowed considerably, with probiotics showing comparable effects to several SSRIs
2. Onset of Action:
   • SSRIs typically required 2-4 weeks for initial effects
   • Probiotics showed a more gradual onset, with optimal effects often emerging after 6-8 weeks of consistent use
3. Durability of Effect:
   • Both interventions maintained efficacy over the study periods (typically 8-12 weeks)
   • Limited long-term data beyond 6 months for probiotics
4. Subgroup Analyses:
   • Probiotics showed stronger effects in individuals with comorbid gastrointestinal symptoms
   • SSRIs demonstrated more consistent effects across different anxiety subtypes
   • Multi-strain probiotic formulations outperformed single-strain products
5. Tolerability and Adherence:
   • Probiotics had significantly lower discontinuation rates due to adverse effects (3.2% vs. 12.7% for SSRIs)
   • Overall adherence rates were comparable between groups

Comparative Efficacy Table

Expert Interpretations

Dr. Michael Chen, lead author of the 2025 meta-analysis, noted: “For individuals with mild anxiety, probiotics offer an efficacy profile approaching that of conventional SSRIs, but with a substantially more favorable side effect profile. This makes them a particularly attractive option for those who are hesitant to begin pharmacotherapy or who experience troublesome side effects from SSRIs.”

Dr. Sarah Thompson, a clinical psychologist specializing in anxiety disorders, offered a more cautious interpretation: “While these findings are promising, it’s important to remember that probiotics should not be viewed as a replacement for established treatments in moderate to severe anxiety. However, for mild anxiety, they represent a viable option that can be considered alongside psychotherapy and lifestyle modifications.”

Mechanisms Underlying Probiotic Effects on Anxiety

Understanding the biological mechanisms through which probiotics exert anxiolytic effects provides important context for their clinical application.

Neurotransmitter Modulation

Several probiotic strains can influence neurotransmitter systems implicated in anxiety:

1. GABA Production: Certain Lactobacillus and Bifidobacterium strains can produce gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the brain
2. Serotonin Pathway Influence: Probiotics can affect tryptophan metabolism and serotonin availability, similar to the target of SSRIs but through different mechanisms
3. Dopamine Regulation: Some probiotic strains influence dopaminergic activity, which may contribute to anxiolytic effects

Inflammatory Pathways

Chronic low-grade inflammation has been implicated in anxiety disorders. Probiotics may reduce anxiety partly through anti-inflammatory effects:

1. Reduction of Pro-inflammatory Cytokines: Probiotics can decrease levels of IL-6, TNF-α, and other inflammatory markers
2. Increase in Anti-inflammatory Compounds: Certain strains promote production of IL-10 and other anti-inflammatory mediators
3. Gut Barrier Enhancement: By strengthening intestinal barrier function, probiotics may prevent translocation of inflammatory molecules into systemic circulation

Stress Response Modulation

The hypothalamic-pituitary-adrenal (HPA) axis, the body’s primary stress response system, is often dysregulated in anxiety disorders:

1. Cortisol Regulation: Probiotics can normalize cortisol levels and daily cortisol patterns
2. Stress Reactivity Reduction: Probiotic supplementation may dampen exaggerated stress responses
3. Autonomic Nervous System Balance: Some strains appear to promote parasympathetic activity, counteracting the sympathetic dominance seen in anxiety

Microbiome Composition Changes

Beyond direct effects, probiotics can shift the overall gut microbiome composition in ways that may benefit mental health:

1. Increased Microbial Diversity: Higher diversity is associated with better mental health outcomes
2. Beneficial Species Enhancement: Probiotics can increase populations of bacteria associated with positive mental health
3. Pathobiont Reduction: Some probiotics competitively inhibit potentially harmful bacterial species

Clinical Implementation: Practical Considerations

For healthcare providers considering probiotics for patients with mild anxiety, several practical aspects deserve attention.

Patient Selection

Probiotics may be particularly suitable for:

• Individuals with mild anxiety who prefer non-pharmacological approaches
• Patients with comorbid gastrointestinal symptoms
• Those who have experienced or are concerned about SSRI side effects
• Individuals seeking complementary approaches alongside psychotherapy
• Patients with contraindications to SSRIs

Probiotics may be less suitable for:

• Severe anxiety requiring rapid symptom control
• Individuals with compromised immune function
• Patients with certain serious medical conditions

Probiotic Selection

When recommending probiotics for anxiety, consider:

1. Strain Specificity: Focus on formulations containing evidence-backed strains (L. rhamnosus, B. longum, etc.)
2. Multi-Strain Advantage: Products containing multiple complementary strains generally show stronger effects
3. Colony-Forming Units (CFUs): Higher potency products (≥10 billion CFUs) may be more effective
4. Quality Assurance: Recommend products from reputable manufacturers with third-party testing
5. Formulation: Consider delivery format (capsules, powders, fortified foods) based on patient preference

Dosing and Duration

Based on available evidence:

• Typical Dosage: 1-10 billion CFUs daily, depending on the specific formulation
• Timing: Consistent daily administration, ideally at the same time each day
• Duration: Minimum 8 weeks to assess efficacy, with many patients benefiting from longer-term use
• Monitoring: Reassess at 4, 8, and 12 weeks to evaluate response

Integration with Other Treatments

Probiotics can be effectively integrated with other anxiety interventions:

1. Combination with Psychotherapy: Probiotics may complement cognitive-behavioral therapy and other evidence-based psychotherapies
2. Adjunct to Pharmacotherapy: For some patients, probiotics may be used alongside reduced doses of SSRIs
3. Lifestyle Synergies: Probiotics appear to work synergistically with exercise, stress management techniques, and dietary modifications
4. Prebiotic Consideration: Adding prebiotic fibers may enhance probiotic efficacy by providing substrate for beneficial bacteria

Comparative Analysis: Advantages and Limitations

A balanced assessment of probiotics versus SSRIs for mild anxiety must consider the relative strengths and weaknesses of each approach.

Advantages of Probiotics

1. Safety Profile: Minimal serious adverse effects, even with long-term use
2. Accessibility: Available without prescription in most jurisdictions
3. Stigma Reduction: May be more acceptable to patients reluctant to take psychiatric medications
4. Holistic Benefits: Potential additional benefits for digestive health, immune function, and overall wellbeing
5. Complementary Approach: Can be easily combined with other treatments

Limitations of Probiotics

1. Variability in Products: Quality, potency, and strain composition vary widely between products
2. Slower Onset: Typically require longer treatment duration to achieve maximum benefits
3. Less Robust Evidence Base: Though growing rapidly, still has fewer large-scale, long-term studies than SSRIs
4. Regulatory Oversight: Less stringent regulation compared to pharmaceuticals
5. Insurance Coverage: Often not covered by health insurance plans

Advantages of SSRIs

1. Established Efficacy: Decades of research supporting effectiveness
2. Broader Indication Range: Effective across the spectrum of anxiety severity
3. Standardized Dosing: Clear guidelines for administration and dose adjustment
4. Regulatory Approval: Formal approval for anxiety disorders by FDA and similar agencies
5. Insurance Coverage: Typically covered by health insurance plans

Limitations of SSRIs

1. Side Effect Burden: Significant proportion of patients experience troublesome side effects
2. Discontinuation Challenges: Can cause withdrawal symptoms when stopped
3. Sexual Dysfunction: High rates of sexual side effects affecting quality of life
4. Delayed Onset: Typically require 2-4 weeks for initial therapeutic effects
5. Stigma Concerns: Some patients reluctant to take psychiatric medications

Patient Perspectives and Experiences

Understanding real-world patient experiences provides valuable context beyond clinical trial data.

Patient Testimonials

SSRI Experience – Mark, 34:
“Sertraline definitely helped reduce my anxiety, but the sexual side effects and emotional blunting were difficult to accept. I felt better but also somehow less like myself. After a year, I worked with my doctor to taper off and explore alternatives.”

Probiotic Experience – Jennifer, 29:
“I was skeptical about probiotics helping my anxiety, but after about six weeks, I noticed I was ruminating less and feeling more emotionally balanced. The effects were subtle but meaningful, and without the side effects I experienced on SSRIs. They haven’t eliminated my anxiety completely, but they’ve made it much more manageable.”

Combined Approach – David, 42:
“For me, the combination has worked best. I take a lower dose of escitalopram than I used to, plus a daily probiotic. My psychiatrist was open to this approach, and I feel I’m getting the benefits of both with fewer side effects than when I was on a higher dose of medication alone.”

Common Patient Questions

Based on clinical experience, these are questions frequently asked by patients considering probiotics for anxiety:

1. “How long will it take to notice effects from probiotics?”
   Most people begin to notice subtle improvements in 4-6 weeks, with more substantial benefits often emerging after 8-12 weeks of consistent use.
2. “Can I take probiotics alongside my current anxiety medication?”
   Generally yes, probiotics can be safely used alongside most anxiety medications, including SSRIs. Always inform your healthcare provider about all supplements you’re taking.
3. “Will probiotics completely eliminate my anxiety?”
   Probiotics typically provide modest to moderate anxiety reduction rather than complete symptom elimination. They may be most effective as part of a comprehensive approach including therapy and lifestyle modifications.
4. “Are there any people who shouldn’t take probiotics?”
   Individuals with severely compromised immune systems, certain serious medical conditions, or those who have recently undergone surgery should consult a healthcare provider before starting probiotics.
5. “What happens if I stop taking probiotics?”
   Unlike SSRIs, probiotics typically don’t cause withdrawal symptoms when discontinued. However, their beneficial effects may gradually diminish over time if supplementation is stopped.

Future Directions in Probiotics and Mental Health Research

As we look toward the future of anxiety treatment, several promising research directions are emerging at the intersection of gut health and mental wellbeing.

Personalized Probiotic Therapy

One of the most exciting frontiers is the development of personalized probiotic interventions based on individual microbiome profiles:

1. Microbiome Testing: Advanced gut microbiome analysis is becoming more accessible, allowing for identification of specific microbial imbalances that may contribute to anxiety
2. Strain-Specific Targeting: Rather than one-size-fits-all approaches, future treatments may involve selecting specific probiotic strains based on an individual’s unique microbiome deficiencies
3. Precision Formulations: Custom probiotic blends tailored to address specific neurochemical imbalances associated with an individual’s anxiety presentation

Dr. Rebecca Johnson, Director of the Microbiome-Brain Research Institute, predicts: “By 2027, I believe we’ll have clinically validated algorithms that can analyze a patient’s microbiome data and recommend specific probiotic strains most likely to benefit their particular anxiety profile.”

Novel Delivery Systems

Improving the delivery and efficacy of probiotics represents another important research direction:

1. Encapsulation Technologies: Advanced encapsulation methods to protect probiotics from stomach acid and ensure delivery to target areas of the intestine
2. Controlled Release Formulations: Systems that release probiotics gradually for more consistent effects
3. Targeted Intestinal Delivery: Methods to deliver specific strains to particular regions of the gut where they can exert maximum benefit
4. Shelf-Stable Innovations: Improvements in probiotic stability to maintain potency without refrigeration

Synbiotic Approaches

The combination of probiotics with prebiotics (synbiotics) shows particular promise:

1. Strain-Specific Prebiotic Pairing: Identifying which prebiotic fibers best support the growth of specific anxiety-reducing probiotic strains
2. Optimized Ratios: Determining ideal proportions of pre- and probiotics for maximum anxiolytic effects
3. Temporal Considerations: Research into whether sequential administration (prebiotics followed by probiotics) may be more effective than simultaneous intake

Psychobiotics: The Next Generation

The term “psychobiotics” refers to live organisms that, when ingested in adequate amounts, produce mental health benefits. This emerging field is expanding beyond traditional probiotics:

1. Engineered Probiotics: Genetically modified probiotic strains designed to produce specific neurotransmitters or neuroactive compounds
2. Postbiotics: Beneficial compounds produced by probiotics that may have direct effects on brain function, potentially offering more standardized interventions
3. Paraprobiotics: Inactivated microbial cells that retain beneficial properties without the challenges of maintaining live organisms

Integration with Digital Health

The intersection of probiotic interventions with digital health technologies offers novel possibilities:

1. Real-time Symptom Tracking: Apps that correlate probiotic intake with anxiety symptoms, sleep quality, and other relevant metrics
2. Adherence Support: Digital tools to improve compliance with probiotic regimens
3. Virtual Care Integration: Telehealth platforms that incorporate microbiome data and probiotic recommendations into comprehensive anxiety management
4. AI-Driven Recommendations: Machine learning algorithms that predict individual responses to specific probiotic strains based on multiple biological and behavioral variables

Expanded Clinical Applications

Research is exploring the potential of probiotics beyond mild anxiety:

1. Comorbid Conditions: Investigating efficacy for anxiety with concurrent depression, PTSD, or other mental health conditions
2. Developmental Considerations: Age-specific formulations and protocols for children, adolescents, and older adults
3. Adjunctive Therapy: Optimizing probiotics as complements to psychotherapy, particularly cognitive-behavioral approaches
4. Prevention Applications: Exploring whether probiotics might prevent anxiety disorders in high-risk populations

Implementation Challenges and Considerations

Despite promising research, several challenges must be addressed for probiotics to become a mainstream anxiety treatment option.

Regulatory Landscape

The regulatory status of probiotics for mental health applications remains complex:

1. Health Claim Limitations: In most jurisdictions, probiotics cannot make specific mental health claims without meeting pharmaceutical-level evidence requirements
2. Quality Standards: Need for more rigorous manufacturing standards and quality control for probiotic products marketed for mental health
3. Clinical Guidelines: Development of official clinical guidelines for probiotic use in anxiety management
4. Insurance Coverage: Advocacy for insurance reimbursement of evidence-based probiotic interventions

Healthcare Provider Education

Many healthcare providers lack sufficient knowledge about the gut-brain axis and probiotic applications for mental health:

1. Medical Curriculum Integration: Need for expanded education on microbiome science in medical, nursing, and psychology training programs
2. Continuing Education: Development of specialized continuing education for practitioners on probiotic applications in mental health
3. Interdisciplinary Collaboration: Fostering communication between gastroenterologists, psychiatrists, psychologists, and primary care providers

Patient Education and Expectations

Managing patient expectations and providing accurate information is crucial:

1. Realistic Benefit Communication: Ensuring patients understand the modest effect sizes and gradual onset of probiotic benefits
2. Product Selection Guidance: Helping patients navigate the overwhelming array of probiotic products
3. Integration with Other Approaches: Emphasizing that probiotics typically work best as part of a comprehensive approach to anxiety management
4. Misinformation Counteraction: Addressing exaggerated claims and misinformation about probiotic “miracle cures”

Practical Decision-Making Framework

For healthcare providers and patients considering probiotics versus SSRIs for mild anxiety, the following decision framework may be helpful:

Consider Probiotics as First-Line When:

• Patient has mild anxiety without severe functional impairment
• Patient expresses preference for non-pharmacological approaches
• Concurrent gastrointestinal symptoms are present
• Patient has previously experienced troublesome SSRI side effects
• Patient is at higher risk for SSRI adverse effects
• Anxiety symptoms appear linked to digestive function

Consider SSRIs as First-Line When:

• Anxiety symptoms are moderate to severe
• Rapid symptom control is needed
• Patient has comorbid conditions known to respond well to SSRIs
• Patient has previously responded well to SSRIs without significant side effects
• Patient preference aligns with SSRI treatment
• Limited response to previous probiotic trials

Consider Combined Approach When:

• Partial response to either intervention alone
• Complex presentation with both psychological and gastrointestinal components
• Patient preference for integrative approach
• Desire to minimize SSRI dosage while maintaining efficacy
• Previous positive response to both modalities

Conclusion: A Paradigm Shift in Anxiety Treatment

The 2025 meta-analysis comparing probiotics and SSRIs for mild anxiety represents a significant milestone in our understanding of alternative approaches to anxiety management. While SSRIs remain an important and effective treatment option, particularly for moderate to severe anxiety, the comparable efficacy of probiotics for mild anxiety—coupled with their superior side effect profile—suggests we may be witnessing a paradigm shift in first-line approaches for milder forms of anxiety.

Dr. Emily Rodriguez, Director of Integrative Psychiatry at Stanford University, summarizes the current state of evidence: “What’s most compelling about the probiotic research is not that it challenges conventional treatments, but that it expands our toolkit with complementary approaches that may be particularly suitable for certain patients. The gut-brain axis represents one of the most promising frontiers in mental health research, offering new pathways to address conditions that affect millions worldwide.”

As research continues to evolve, the most prudent approach appears to be one of thoughtful integration—recognizing the legitimate place of both conventional pharmaceuticals and emerging microbiome-based interventions in our treatment armamentarium. For patients with mild anxiety, probiotics represent a scientifically-supported option that merits serious consideration, either as a first-line approach or as part of a comprehensive treatment strategy.

The ultimate beneficiaries of this expanding evidence base are patients themselves, who now have more options than ever to address anxiety symptoms in ways that align with their preferences, values, and individual health profiles. As we continue to unravel the complex connections between gut health and mental wellbeing, the future of anxiety treatment looks increasingly personalized, integrative, and holistic.