Mycobacterium vaccae NCTC 11659, a Soil-Derived Bacterium with Stress Resilience Properties, Modulates the Proinflammatory Effects of LPS in Macrophages.

Inflammatory conditions, including allergic asthma and conditions in which chronic low-grade inflammation is a risk factor, such as stress-related psychiatric disorders, are prevalent and are a significant cause of disability worldwide. Novel approaches for the prevention and treatment of these disorders are needed. One approach is the use of immunoregulatory microorganisms, such as Mycobacterium vaccae NCTC 11659, which have anti-inflammatory, immunoregulatory, and stress-resilience properties. However, little is known about how M. vaccae NCTC 11659 affects specific immune cell targets, including monocytes, which can traffic to peripheral organs and the central nervous system and differentiate into monocyte-derived macrophages that, in turn, can drive inflammation and neuroinflammation. In this study, we investigated the effects of M. vaccae NCTC 11659 and subsequent lipopolysaccharide (LPS) challenge on gene expression in human monocyte-derived macrophages. THP-1 monocytes were differentiated into macrophages, exposed to M. vaccae NCTC 11659 (0, 10, 30, 100, 300 µg/mL), then, 24 h later, challenged with LPS (0, 0.5, 2.5, 250 ng/mL), and assessed for gene expression 24 h following challenge with LPS. Exposure to M. vaccae NCTC 11659 prior to challenge with higher concentrations of LPS (250 ng/mL) polarized human monocyte-derived macrophages with decreased IL12A, IL12B, and IL23A expression relative to IL10 and TGFB1 mRNA expression. These data identify human monocyte-derived macrophages as a direct target of M. vaccae NCTC 11659 and support the development of M. vaccae NCTC 11659 as a potential intervention to prevent stress-induced inflammation and neuroinflammation implicated in the etiology and pathophysiology of inflammatory conditions and stress-related psychiatric disorders.

Prelinguistic gesture and developmental abilities: A multi-ethnic comparative study.

The present study examined the frequency of gesture use and the relationship between frequency of gesture use and developmental abilities in typically developing 9- to 15-month-old, prelinguistic Hispanic and non-Hispanic White children. Data was collected through parent questionnaires, the Mullen Scales of Early Learning (MSEL), and two, 15-min video samples for each participant (semi-structured and structured settings). All video samples were coded for the frequency of the following gestures: total frequency, behavior regulation, social interaction, and joint attention. Results showed that children from both ethnicities used fewer gestures in a semi-structured setting in comparison to a structured setting and non-Hispanic White children produced higher frequencies of behavior regulation gestures and joint attention gestures, but lower frequencies of social interaction gestures. When controlling for ethnicity, gender, and age total frequency of gesture and frequencies of behavior regulation and social interaction were predictive of various developmental abilities. Furthermore, participant gender, age, and ethnicity were significantly related to various developmental abilities explored. These relationships were dependent upon setting. An understanding of the use of gesture and the relationship between gesture use and developmental abilities in prelinguistic children from different ethnic backgrounds has implication for early identification of delays and differences and is important to consider when exploring the connection between gesture and language and whether there are gesture-language, gesture-motor, and/or gesture-cognition integrated systems.

Frequency of Gesture Use and Language in Typically Developing Prelinguistic Children.

PURPOSE: The aim of this study was to examine the relationship between frequency of gesture use and language with a consideration for the effect of age and setting on frequency of gesture use in prelinguistic typically developing children. METHOD: Participants included a total of 54 typically developing infants and toddlers between the ages of 9 months and 15 months separated into two age ranges, 9-12 months and 12-15 months. All participants were administered the Mullen's Scale of Early Learning and two gesture samples were obtained: one sample in a structured setting and the other in an unstructured setting. Gesture samples were coded by research assistants blind to the purpose of the research study and total frequency and frequencies for the following gesture types were calculated: behavior regulation, social interaction, and joint attention (Bruner, 1983). RESULTS: Results indicated that both age and setting have a significant effect on frequency of gesture use and frequency of gesture is correlated to receptive and expressive language abilities; however, these relationships are dependent upon the gesture type examined. CONCLUSIONS: These findings further our understanding of the relationship between gesture use and language and support the concept that frequency of gesture is related to language abilities. This is meaningful because gestures are one of the first forms of intentional communication, allowing for early identification of language abilities at a young age.

Effects of Immunization With the Soil-Derived Bacterium Mycobacterium vaccae on Stress Coping Behaviors and Cognitive Performance in a "Two Hit" Stressor Model.

Previous studies demonstrate that Mycobacterium vaccae NCTC 11659 (M. vaccae), a soil-derived bacterium with anti-inflammatory and immunoregulatory properties, is a potentially useful countermeasure against negative outcomes to stressors. Here we used male C57BL/6NCrl mice to determine if repeated immunization with M. vaccae is an effective countermeasure in a "two hit" stress exposure model of chronic disruption of rhythms (CDR) followed by acute social defeat (SD). On day -28, mice received implants of biotelemetric recording devices to monitor 24-h rhythms of locomotor activity. Mice were subsequently treated with a heat-killed preparation of M. vaccae (0.1 mg, administered subcutaneously on days -21, -14, -7, and 27) or borate-buffered saline vehicle. Mice were then exposed to 8 consecutive weeks of either stable normal 12:12 h light:dark (LD) conditions or CDR, consisting of 12-h reversals of the LD cycle every 7 days (days 0-56). Finally, mice were exposed to either a 10-min SD or a home cage control condition on day 54. All mice were exposed to object location memory testing 24 h following SD. The gut microbiome and metabolome were assessed in fecal samples collected on days -1, 48, and 62 using 16S rRNA gene sequence and LC-MS/MS spectral data, respectively; the plasma metabolome was additionally measured on day 64. Among mice exposed to normal LD conditions, immunization with M. vaccae induced a shift toward a more proactive behavioral coping response to SD as measured by increases in scouting and avoiding an approaching male CD-1 aggressor, and decreases in submissive upright defensive postures. In the object location memory test, exposure to SD increased cognitive function in CDR mice previously immunized with M. vaccae. Immunization with M. vaccae stabilized the gut microbiome, attenuating CDR-induced reductions in alpha diversity and decreasing within-group measures of beta diversity. Immunization with M. vaccae also increased the relative abundance of 1-heptadecanoyl-sn-glycero-3-phosphocholine, a lysophospholipid, in plasma. Together, these data support the hypothesis that immunization with M. vaccae stabilizes the gut microbiome, induces a shift toward a more proactive response to stress exposure, and promotes stress resilience.