Immunomodulation by xylan and carrageenan-type polysaccharides from red seaweeds: Anti-inflammatory, wound healing, cytoprotective, and anticoagulant activities.

The immunomodulatory properties of the polysaccharides (carrageenan, xylan) from Chondrus crispus (CC), Ahnfeltiopsis devoniensis (AD), Sarcodiotheca gaudichaudii (SG) and Palmaria palmata (PP) algal species were studied. Using RAW264.7 macrophages, we investigated the proliferation and migration capacity of different extracts along with their immunomodulatory activities, including nitric oxide (NO) production, phagocytosis, and secretion of pro-inflammatory cytokines. Polysaccharides from C. crispus and S. gaudichaudii effectively mitigated inflammation and improved scratch-wound healing. Polysaccharide fractions extracted under cold conditions (25 °C), including CC-1A, SG-1A and SG-1B stimulated cell proliferation, while fractions extracted under hot conditions (95 °C), including CC-3A, CC-2B and A. devoniensis (AD-3A), inhibited cell proliferation after 48 h. Furthermore, RAW264.7 cells treated with the fractions CC-3A, AD-1A, and SG-2A significantly reduced LPS-stimulated NO secretion over 24 h. Phagocytosis was significantly improved by treatment with C. crispus (CC-2B, CC-3B) and A. devoniensis (AD-3A) fractions. RAW264.7 cells treated with the CC-2A and SG-1A fractions showed elevated TGF-ß1 expression without affecting TNF-α expression at 24 h. Polysaccharide fractions of A. devoniensis (ι/κ hybrid carrageenan; AD-2A, AD-3A) showed the highest anti-coagulation activity. CC-2A and SG-1A fractions enhanced various bioactivities, suggesting they are candidates for skin-health applications. The carrageenan fractions (CC-3A: λ-, µ-carrageenan, SG-2A: ν-, ι-carrageenan) tested herein showed great potential for developing anti-inflammatory and upscaled skin-health applications.

Bioengineered Wheat Arabinoxylan - Fostering Next-Generation Prebiotics Targeting Health-Related Gut Microbes.

Dietary prebiotic fibers play an important role in modulating gut microbiota by enhancing the abundance of beneficial microorganisms and their bioactive metabolites. However, dietary fibers are a structurally heterogeneous class of polysaccharides, varying in molar mass, branching patterns, and monosaccharide composition, which could influence their utilization by various gut microorganisms. The present study aimed to investigate the effects of molar mass and chemical structure of wheat arabinoxylan fiber (AX) on the growth and metabolism of two key gut resident bacteria (Faecalibacterium prausnitzii and Lacticaseibacillus rhamnosus LGG), which are linked to human health. For this purpose, low, medium, and high molar masses of AX (LAX, MAX, and HAX, respectively) were modified with specific α-arabinofuranosidases to leave only singly substituted, only doubly substituted, or unsubstituted xylose units. Almost all the modified AX samples showed a better prebiotic score than unmodified AX for different molar masses. The modified LAX exhibited a better prebiotic effect than HAX and MAX. In addition, LAX, with doubly substituted xylose units, exhibited the highest prebiotic potential and SCFA production by both microorganisms. Furthermore, AX, either singly or doubly substituted, had a consistent impact on L. rhamnosus growth, whereas AX, with all arabinose residues removed, had a greater impact on F. prausnitzii. These findings support the potential of bioengineered AX as next-generation prebiotics targeting health-related gut microbes.

A Two Bacteriocinogenic Ligilactobacillus Strain Association Inhibits Growth, Adhesion, and Invasion of Salmonella in a Simulated Chicken Gut Environment.

In this study, we aimed to develop a protective probiotic coculture to inhibit the growth of Salmonella enterica serovar Typhimurium in the simulated chicken gut environment. Bacterial strains were isolated from the digestive mucosa of broilers and screened in vitro against Salmonella Typhimurium ATCC 14028. A biocompatibility coculture test was performed, which identified two biocompatible strains, Ligilactobacillus salivarius UO.C109 and Ligilactobacillus saerimneri UO.C121 with high inhibitory activity against Salmonella. The cell-free supernatant (CFS) of the selected isolates exhibited dose-dependent effects, and the inhibitory agents were confirmed to be proteinaceous by enzymatic and thermal treatments. Proteome and genome analyses revealed the presence of known bacteriocins in the CFS of L. salivarius UO.C109, but unknown for L. saerimneri UO.C121. The addition of these selected probiotic candidates altered the bacterial community structure, increased the diversity of the chicken gut microbiota challenged with Salmonella, and significantly reduced the abundances of Enterobacteriaceae, Parasutterlla, Phascolarctobacterium, Enterococcus, and Megamonas. It also modulated microbiome production of short-chain fatty acids (SCFAs) with increased levels of acetic and propionic acids after 12 and 24 h of incubation compared to the microbiome challenged with S. Typhimurium. Furthermore, the selected probiotic candidates reduced the adhesion and invasion of Salmonella to Caco-2 cells by 37-39% and 51%, respectively, after 3 h of incubation, compared to the control. These results suggest that the developed coculture probiotic strains has protective activity and could be an effective strategy to control Salmonella infections in poultry.

Evidence of the Dysbiotic Effect of Psychotropics on Gut Microbiota and Capacity of Probiotics to Alleviate Related Dysbiosis in a Model of the Human Colon.

Growing evidence indicates that non-antibiotic therapeutics significantly impact human health by modulating gut microbiome composition and metabolism. In this study, we investigated the impact of two psychotropic drugs, aripiprazole and (S)-citalopram, on gut microbiome composition and its metabolic activity, as well as the potential of probiotics to attenuate related dysbiosis using an ex vivo model of the human colon. After 48 h of fermentation, the two psychotropics demonstrated distinct modulatory effects on the gut microbiome. Aripiprazole, at the phylum level, significantly decreased the relative abundances of Firmicutes and Actinobacteria, while increasing the proportion of Proteobacteria. Moreover, the families Lachnospiraceae, Lactobacillaceae, and Erysipelotrichaceae were also reduced by aripiprazole treatment compared to the control group. In addition, aripiprazole lowered the levels of butyrate, propionate, and acetate, as measured by gas chromatography (GC). On the other hand, (S)-citalopram increased the alpha diversity of microbial taxa, with no differences observed between groups at the family and genus level. Furthermore, a probiotic combination of Lacticaseibacillus rhamnosus HA-114 and Bifidobacterium longum R0175 alleviated gut microbiome alterations and increased the production of short-chain fatty acids to a similar level as the control. These findings provide compelling evidence that psychotropics modulate the composition and function of the gut microbiome, while the probiotic can mitigate related dysbiosis.

Draft Genome Sequences of 18 Bacteroidetes Strains Isolated from a Human Stool Sample.

We announce the draft genome sequences of 12 Bacteroides, 4 Phocaeicola, and 2 Parabacteroides strains, among which was a newly isolated species, Bacteroidaceae bacterium UO.H1004. These isolates produce health-benefiting short-chain fatty acids (SCFAs) and the neurotransmitter γ-aminobutyric acid (GABA) in various concentrations.

Neuromicrobiology, an emerging neurometabolic facet of the gut microbiome?

The concept of the gut microbiome is emerging as a metabolic interactome influenced by diet, xenobiotics, genetics, and other environmental factors that affect the host's absorption of nutrients, metabolism, and immune system. Beyond nutrient digestion and production, the gut microbiome also functions as personalized polypharmacy, where bioactive metabolites that our microbes excrete or conjugate may reach systemic circulation and impact all organs, including the brain. Appreciable evidence shows that gut microbiota produce diverse neuroactive metabolites, particularly neurotransmitters (and their precursors), stimulating the local nervous system (i.e., enteric and vagus nerves) and affecting brain function and cognition. Several studies have demonstrated correlations between the gut microbiome and the central nervous system sparking an exciting new research field, neuromicrobiology. Microbiome-targeted interventions are seen as promising adjunctive treatments (pre-, pro-, post-, and synbiotics), but the mechanisms underlying host-microbiome interactions have yet to be established, thus preventing informed evidence-based therapeutic applications. In this paper, we review the current state of knowledge for each of the major classes of microbial neuroactive metabolites, emphasizing their biological effects on the microbiome, gut environment, and brain. Also, we discuss the biosynthesis, absorption, and transport of gut microbiota-derived neuroactive metabolites to the brain and their implication in mental disorders.

Survival and Interplay of γ-Aminobutyric Acid-Producing Psychobiotic Candidates with the Gut Microbiota in a Continuous Model of the Human Colon.

Over decades, probiotic research has focused on their benefits to gut health. Recently, the gut microbiota has been proven to share bidirectional connections with the brain through the gut-brain axis. Therefore, the manipulation of this axis via probiotics has garnered interest. We have recently isolated and characterized in vitro probiotic candidates producing γ-aminobutyric acid (GABA), a major neuromodulator of the enteric nervous system. This study investigates the growth and competitiveness of selected GABA-producing probiotic candidates (Bifidobacterium animalis, Streptococcus thermophilus, and Lactobacillus delbrueckii subsp. bulgaricus) in the presence of human gut microbiota ex vivo in a model mimicking physiological and microbiological conditions of the human proximal colon. Supplementation with GABA-producing probiotic candidates did not affect the overall gut microbiota diversity over 48 h of treatment. However, these candidates modulated the microbiota composition, especially by increasing the Bacteroidetes population, a key gut microbe associated with anti-inflammatory activities. The level of microbiota-generated SCFAs within 12 h of treatment was also increased, compared to the control group. Results from this study demonstrate the probiotic potential of the tested GABA-producing bacteria and their impact on gut microbiota structure and metabolism, suggesting their suitability for gut health-promoting applications.

The Untapped Potential of Ginsenosides and American Ginseng Berry in Promoting Mental Health via the Gut-Brain Axis.

Despite the popularity of the ginseng (Panax) root in health research and on the market, the ginseng berry's potential remains relatively unexplored. Implementing ginseng berry cultivations and designing berry-derived products could improve the accessibility to mental health-promoting nutraceuticals. Indeed, the berry could have a higher concentration of neuroprotective and antidepressant compounds than the root, which has already been the subject of research demonstrating its efficacy in the context of neuroprotection and mental health. In this review, data on the berry's application in supporting mental health via the gut-brain axis is compiled and discussed.

An agar-based bioassay for accurate screening of the total antioxidant capacity of lactic acid bacteria cell-free supernatants.

This study aims to develop a new, simple, and efficient method for estimating the total antioxidant capacity of lactic acid bacteria-cell free supernatant. The bioassay is based on diffusion and reduction of permanganate in agar medium under acidic conditions where the Mn7+ ions are quantitatively oxidized to Mn2+ and shift from an intense purple color to colorless. Hence, the reaction enables fast detection of the bleaching diameter during diffusion of the sample in permanganate agar. This bleaching diameter is correlated to the reducing power of the substance tested. The method was tested and validated to quantify the total antioxidant capacity of culture supernatants of probiotic strains (Lacticaseibacillus rhamnosus LGG and Lactiplantibacillus plantarum 299v) and 25 lactic acid bacteria isolated from a human intestinal origin and compared to the PRAC and DPPH methods. The results were treated statistically by analysis of variance. This method proved to be linear (R2 in the linear experiment of ascorbic acid was 0,99), precise with repeatability intraday RSD of 2.07 to 5.5% and intermediate precision RSD of 2.95 to 5.53%, and accurate (100.29 to 108.58%) at 30 min, 1 h, and 4 h in the selected range of 1.5-5.5 mM of ascorbic acid. The developed permanganate agar reduction bioassay is a fast, reliable, and cost-effective technique for the prescreening and detecting the total antioxidant capacity of supernatants of lactic acid bacteria and possibly other sources of natural antioxidants.

Screening, characterization and growth of γ-aminobutyric acid-producing probiotic candidates from food origin under simulated colonic conditions.

AIMS: This study aims to isolate probiotic bacteria candidates from various starter cultures and fermented foods and characterize their ability to produce γ-aminobutyric acid (GABA). GABA is a major inhibitory neuromediator of the central and enteric nervous systems with a role in several health disorders. METHODS AND RESULTS: Fourteen strains of lactic acid bacteria were isolated from food environment and screened for the presence of the glutamate decarboxylase (gadB) gene using PCR and GAD enzymatic assay. The identified potent GABA-producers included Strep. thermophilus, Lactiplantibacillus plantarum and Lact. delbrueckii subsp. bulgaricus. GC-FID analyses confirmed the high GABA production capacity of Strep. thermophilus ST16 (1641.5 ± 154.15 µmol l-1 ), Strep. thermophilus ST8 (1724.5 ± 48.08 µmol/L). To a lesser extent, Bif. animalis ST20, Lact. acidophilus LP16-2 and Ent. faecium ST3 produced 947.5 ± 70.71, 918.0 ± 121.42, and 907.83 ± 55.15 µmol/L of GABA, respectively. These potent strains were able to grow and produce GABA in MRS broth and pre-fermented Macfarlane broth, the latter medium mimicking the nutrient and metabolome composition encountered in the colon. The identified bioactive strains exhibited strong biological safety and probiotic potential profiles as indicated by sensitivity to antibiotics, absence of virulence factors and survival in gastrointestinal conditions. CONCLUSIONS: Several GABA producing probiotic candidates, including Bif. animals ST20, Strep. thermophilus ST8, Lact. acidophilus LP16-2, L. plantarum LP6 & LP9, and Ent. faecium ST3, have shown potential to grow under simulated colonic conditions. SIGNIFICANCE AND IMPACT OF STUDY: Findings from this study provide evidence of the suitability of the isolated GABA-producing probiotic candidates for the development of health-oriented functional food products.

Bacteriocinogenic probiotics as an integrated alternative to antibiotics in chicken production - why and how?

The misuse of antibiotics in the livestock industry has played an important role in the spread of resistant superbugs with severe health implications for humans. With the recent ban on the use of antibiotics in poultry and poultry feed in Canada and the USA, poultry farmers will have to rely on the use of alternatives to antibiotics (such as feed acidifiers, antibodies, bacteriophages, antimicrobial peptides, prebiotics, and probiotics) to maintain the same productivity and health of their livestock. Of particular interest are bacteriocinogenic probiotics, that is, bacterial strains capable of producing bacteriocins that confer health benefits on the host. These bacterial strains have multiple promising features, such as the ability to attach to the host mucosa, colonize, proliferate, and produce advantageous products such as bacteriocins and short-chain fatty acids. These not only affect pathogenic colonization but improve poultry phenotype as well. Bacteriocins are antimicrobial peptides with multiple promising features such as being non-harmful for human and animal consumption, non-disruptive to the host microbiota eubiosis, non-cytotoxic, and non-carcinogenic. Therefore, bacteriocinogenic probiotics are at the forefront to be excellent candidates for effective replacements to antibiotics. While evidence of their safety and effectiveness is accumulating in vitro and in vivo in inhibiting pathogens while promoting animal health, their safety and history of use in livestock remains unclear and requires additional investigations. In the present paper, we review the safety assessment regulations and commercialization policies on existing and novel bacteriocinogenic and bacteriocin products intended to be used in poultry feed as an alternative to antibiotics.

Gut Microbiota Extracellular Vesicles as Signaling Molecules Mediating Host-Microbiota Communications.

Over the past decade, gut microbiota dysbiosis has been linked to many health disorders; however, the detailed mechanism of this correlation remains unclear. Gut microbiota can communicate with the host through immunological or metabolic signalling. Recently, microbiota-released extracellular vesicles (MEVs) have emerged as significant mediators in the intercellular signalling mechanism that could be an integral part of microbiota-host communications. MEVs are small membrane-bound vesicles that encase a broad spectrum of biologically active compounds (i.e., proteins, mRNA, miRNA, DNA, carbohydrates, and lipids), thus mediating the horizontal transfer of their cargo across intra- and intercellular space. In this study, we provide a comprehensive and in-depth discussion of the biogenesis of microbial-derived EVs, their classification and routes of production, as well as their role in inter-bacterial and inter-kingdom signaling.

Anti-Salmonella Activity and Peptidomic Profiling of Peptide Fractions Produced from Sturgeon Fish Skin Collagen (Huso huso) Using Commercial Enzymes.

This study investigated peptide fractions from fish skin collagen for antibacterial activity against Escherichia coli and Salmonella strains. The collagen was hydrolyzed with six commercial proteases, including trypsin, Alcalase, Neutrase, Flavourzyme, pepsin and papain. Hydrolyzed samples obtained with trypsin and Alcalase had the largest number of small peptides (molecular weight <10 kDa), while the hydrolysate produced with papain showed the lowest degree of hydrolysis and highest number of large peptides. Four hydrolysates were found to inhibit the growth of the Gram-negative bacteria, with papain hydrolysate showing the best activity against E. coli, and Neutrase and papain hydrolysates showing the best activity against S. abony; hydrolysates produced with trypsin and pepsin did not show detectable antibacterial activity. After acetone fractionation of the latter hydrolysates, the peptide fractions demonstrated enhanced dose-dependent inhibition of the growth (colony-forming units) of four Salmonella strains, including S. abony (NCTC 6017), S. typhimurium (ATCC 13311), S. typhimurium (ATCC 14028) and S. chol (ATCC 10708). Shotgun peptidomics analysis of the acetone fractions of Neutrase and papain hydrolysates resulted in the identification of 71 and 103 peptides, respectively, with chain lengths of 6-22 and 6-24, respectively. This work provided an array of peptide sequences from fish skin collagen for pharmacophore identification, structure-activity relationship studies, and further investigation as food-based antibacterial agents against pathogenic microorganisms.

Probiotic and Antifungal Attributes of Levilactobacillus brevis MYSN105, Isolated From an Indian Traditional Fermented Food Pozha.

The use of probiotics and antifungal capabilities of the lactic acid bacteria (LAB) isolated from different niches is a strategy to prepare functional cultures and biopreservatives for food/feed industries. In the present study, LAB strains isolated from an Indian traditional fermented food, Pozha, were evaluated for their probiotic properties and biocontrol potential. A total of 20 LAB isolates were selected from Pozha samples collected aseptically and screened for their antagonistic activity against Fusarium verticillioides. Among the bioactive isolates, Lacticaseibacillus brevis MYSN105 showed the highest antifungal activity in vitro, causing some morphological alterations such as damaged mycelia and deformed conidia. Cell-free supernatant (CFS) from L. brevis MYSN105 at 16% concentration effectively reduced the mycelial biomass to 0.369 g compared to 1.938 g in control. Likewise, the conidial germination was inhibited to 20.12%, and the seed treatment using CFS induced a reduction of spore count to 4.1 × 106 spores/ml compared to 1.1 × 109 spores/ml for untreated seeds. The internal transcribed spacer (ITS) copy number of F. verticillioides decreased to 5.73 × 107 and 9.026 × 107 by L. brevis MYSN105 and CFS treatment, respectively, compared to 8.94 × 1010 in control. The L. brevis MYSN105 showed high tolerance to in vitro gastrointestinal conditions and exhibited high adhesive abilities to intestinal epithelial cell lines. The comparative genome analysis demonstrated specific secondary metabolite region coding for bacteriocin and T3PKS (type III polyketide synthase) possibly related to survival and antimicrobial activity in the gut environment. Our results suggest that L. brevis MYSN105 has promising probiotic features and could be potentially used for developing biological control formulations to minimize F. verticillioides contamination and improve food safety measures.

Dual Inhibition of Salmonella enterica and Clostridium perfringens by New Probiotic Candidates Isolated from Chicken Intestinal Mucosa.

The poultry industry is the fastest-growing agricultural sector globally. With poultry meat being economical and in high demand, the end product's safety is of importance. Globally, governments are coming together to ban the use of antibiotics as prophylaxis and for growth promotion in poultry. Salmonella and Clostridium perfringens are two leading pathogens that cause foodborne illnesses and are linked explicitly to poultry products. Furthermore, numerous outbreaks occur every year. A substitute for antibiotics is required by the industry to maintain the same productivity level and, hence, profits. We aimed to isolate and identify potential probiotic strains from the ceca mucosa of the chicken intestinal tract with bacteriocinogenic properties. We were able to isolate multiple and diverse strains, including a new uncultured bacterium, with inhibitory activity against Salmonella Typhimurium ATCC 14028, Salmonella Abony NCTC 6017, Salmonella Choleraesuis ATCC 10708, Clostridium perfringens ATCC 13124, and Escherichia coli ATCC 25922. The five most potent strains were further characterized for their probiotic potential (i.e., sensitivity to antibiotics and tolerance to gastrointestinal physicochemical conditions). Our analyzed lactobacilli strains exhibited some interesting probiotic features while being inhibitory against targeted pathogens.

Bacteriocins as a new generation of antimicrobials: toxicity aspects and regulations.

In recent decades, bacteriocins have received substantial attention as antimicrobial compounds. Although bacteriocins have been predominantly exploited as food preservatives, they are now receiving increased attention as potential clinical antimicrobials and as possible immune-modulating agents. Infections caused by antibiotic-resistant bacteria have been declared as a global threat to public health. Bacteriocins represent a potential solution to this worldwide threat due to their broad- or narrow-spectrum activity against antibiotic-resistant bacteria. Notably, despite their role in food safety as natural alternatives to chemical preservatives, nisin remains the only bacteriocin legally approved by regulatory agencies as a food preservative. Moreover, insufficient data on the safety and toxicity of bacteriocins represent a barrier against the more widespread use of bacteriocins by the food and medical industry. Here, we focus on the most recent trends relating to the application of bacteriocins, their toxicity and impacts.

Nutritional and therapeutic approaches for protecting human gut microbiota from psychotropic treatments.

Emerging evidence highlighted the essential role played by the microbiota-gut-brain axis in maintaining human homeostasis, including nutrition, immunity, and metabolism. Much recent work has linked the gut microbiota to many psychiatric and neurodegenerative disorders such as depression, schizophrenia, and Alzheimer's disease. Shared gut microbiota alterations or dysbiotic microbiota have been identified in these separate disorders relative to controls. Much attention has focused on the bidirectional interplay between the gut microbiota and the brain, establishing gut dysbiotic status as a critical factor in psychiatric disorders. Still, the antibiotic-like effect of psychotropic drugs, medications used for the treatment of these disorders, on gut microbiota is largely neglected. In this review, we summarize the current findings on the impact of psychotropics on gut microbiota and how their antimicrobial potency can trigger dysbiosis. We also discuss the potential therapeutic strategies, including probiotics, prebiotics, and fecal transplantation, to attenuate the dysbiosis related to psychotropics intake.

Alterations of the Treatment-Naive Gut Microbiome in Newly Diagnosed Hepatitis C Virus Infection.

Gut microbiota dysbiosis has been linked to many heath disorders including hepatitis C virus (HCV) infection. However, profiles of the gut microbiota alterations in HCV are inconsistent in the literature and are affected by the treatment regimens. Using samples collected prior to treatment from newly diagnosed patients, we characterized the gut microbiota structure in HCV patients as compared to healthy controls. Treatment-naive HCV microbiota showed increased diversity, an increased abundance of Prevotella, Succinivibrio, Catenibacterium, Megasphaera, and Ruminococcaceae, and a lower abundance of Bacteroides, Dialister, Bilophila, Streptococcus, parabacteroides, Enterobacteriaceae, Erysipelotrichaceae, Rikenellaceae, and Alistipes. Predicted community metagenomic functions showed a depletion of carbohydrate and lipid metabolism in HCV microbiota along with perturbations of amino acid metabolism. Receiver-operating characteristic analysis identified five disease-specific operational taxonomic units (OTUs) as potential biomarkers of HCV infections. Collectively, our findings reveal the alteration of gut microbiota in treatment naive HCV patients and suggest that gut microbiota may hold diagnostic promise in HCV infection.

Unravelling the antimicrobial action of antidepressants on gut commensal microbes.

Over the past decade, there has been increasing evidence highlighting the implication of the gut microbiota in a variety of brain disorders such as depression, anxiety, and schizophrenia. Studies have shown that depression affects the stability of gut microbiota, but the impact of antidepressant treatments on microbiota structure and metabolism remains underexplored. In this study, we investigated the in vitro antimicrobial activity of antidepressants from different therapeutic classes against representative strains of human gut microbiota. Six different antidepressants: phenelzine, venlafaxine, desipramine, bupropion, aripiprazole and (S)-citalopram have been tested for their antimicrobial activity against 12 commensal bacterial strains using agar well diffusion, microbroth dilution method, and colony counting. The data revealed an important antimicrobial activity (bacteriostatic or bactericidal) of different antidepressants against the tested strains, with desipramine and aripiprazole being the most inhibitory. Strains affiliating to most dominant phyla of human microbiota such as Akkermansia muciniphila, Bifidobacterium animalis and Bacteroides fragilis were significantly altered, with minimum inhibitory concentrations (MICs) ranged from 75 to 800 µg/mL. A significant reduction in bacterial viability was observed, reaching 5 logs cycle reductions with tested MICs ranged from 400 to 600 µg/mL. Our findings demonstrate that gut microbiota could be altered in response to antidepressant drugs.