Disrupted development of the gut microbiota is a contributing cause of childhood malnutrition. Bifidobacterium longum subspecies infantis is a prominent early colonizer of the infant gut that consumes human milk oligosaccharides (HMOs). We found that the absolute abundance of Bifidobacterium infantis is lower in 3- to 24-month-old Bangladeshi infants with severe acute malnutrition (SAM) compared to their healthy age-matched counterparts. A single-blind, placebo-controlled trial (SYNERGIE) was conducted in 2- to 6-month-old Bangladeshi infants with SAM. A commercial U.S. donor–derived B. infantis strain (EVC001) was administered daily with or without the HMO lacto- N -neotetraose for 28 days. This intervention increased fecal B. infantis abundance in infants with SAM, although to levels still 10- to 100-fold lower than in untreated healthy controls. EVC001 treatment promoted weight gain that was associated with reduced intestinal inflammation markers in infants with SAM. We cultured fecal B. infantis strains from Bangladeshi infants and colonized gnotobiotic mice with these cultured strains. The gnotobiotic mice were fed a diet representative of that consumed by 6-month-old Bangladeshi infants, with or without HMO supplementation. One B. infantis strain, Bg_2D9, expressing two gene clusters involved in uptake and utilization of N -glycans and plant-derived polysaccharides, exhibited superior fitness over EVC001. The fitness advantage of Bg_2D9 was confirmed in a gnotobiotic mouse model of mother-to-infant gut microbiota transmission where dams received a pretreatment fecal community from a SAM infant in the SYNERGIE trial. Whether Bg_2D9 is superior to EVC001 for treating malnourished infants who consume a diet with limited breastmilk requires further clinical testing.

Highlights d Mice with microbiota from undernourished children have varied CT vaccine responses d Nutraceutical improves varied vaccine responses to oral CT in gnotobiotic mice d Co-housing mice with responsive (R) and HypoR microbiota improves CT responses d Five bacterial strains plus nutraceutical promotes vaccine efficacy in HypoR animals

Dopamine regulates reproduction in part by modulating neuronal activity within the hypothalamic-pituitary-gonadal (HPG) axis. Previous studies suggested numerous mechanisms by which dopamine exerts inhibitory control over the HPG axis, ultimately changing the levels of sex steroids that regulate reproductive behaviors. However, it is not known whether these mechanisms are conserved across vertebrate species. In particular, it is unknown whether mechanisms underlying dopaminergic control of reproduction are shared between mammals and teleost fish. In mammals, dopamine directly inhibits gonadotropin-releasing hormone (GnRH1) hypothalamic neurons, the gatekeepers for activation of the HPG axis. Here, we demonstrate, for the first time in teleost fish, dopaminergic control of GnRH1 neurons via direct dopamine type-2-like receptor (D2R)-mediated inhibition within the hypothalamus. These results suggest that direct dopaminergic control of GnRH1 neurons via interactions in the hypothalamus is not exclusive to tetrapod reproductive control, but is likely conserved across vertebrate species.

The evolutionary diversification of animal behavior is often associated with changes in the structure and function of nervous systems. Such evolutionary changes arise either through alterations of individual neural components (“mosaically”) or through scaling of the whole brain (“concertedly”). Here we show that the evolution of a courtship behavior in Malawi cichlid fish is associated with rapid, extensive, and specific diversification of orosensory, gustatory centers in the hindbrain. We find that hindbrain volume varies significantly between species that build pit (depression) compared to castle (mound) type bowers and that this trait is evolving rapidly among castle-building species. Molecular analyses of neural activity via immediate early gene expression indicate a functional role for hindbrain structures during bower building. Finally, comparisons of bower building species in neighboring Lake Tanganyika suggest parallel patterns of neural diversification to those in Lake Malawi. Our results suggest that mosaic brain evolution via alterations to individual brain structures is more extensive and predictable than previously appreciated.

31The evolutionary diversification of animal behavior is often associated with changes in 32 the structure and function of nervous systems. Such evolutionary changes arise either through 33 alterations of individual neural components ("mosaically") or through scaling of the whole brain 34 ("concertedly"). Here we show that the evolution of a specific courtship behavior in Malawi 35 cichlid fish, the construction of mating nests known as bowers, is associated with rapid, 36 extensive, and specific diversification of orosensory, gustatory centers in the hindbrain. We find 37 that hindbrain volume varies significantly between species that build pit (depression) compared 38 to castle (mound) type bowers and that hindbrain features evolve rapidly and independently of 39 phylogeny among castle-building species. Using immediate early gene expression, we confirmed 40 a functional role for hindbrain structures during bower building. Comparisons of bower building 41 species in neighboring Lake Tanganyika show patterns of neural diversification parallel to those 42 in Lake Malawi. Our results suggest that mosaic brain evolution via alterations to individual 43 brain structures is more extensive and predictable than previously appreciated. 44 45 behaviors vary widely, as do their neural phenotypes [1]. Evolutionary 63 neuroscience identifies how the brain diversifies over time and space in response to selective 64 pressures [2]. A key goal of evolutionary neuroscience has been to identify whether brain 65 structures evolve independently ("mosaically") or in tandem with each other as they reflect key 66 life history traits, especially behavior [3][4][5][6]. While a number of studies have linked variation in 67 brain structure with other traits across evolutionary time [2, 7-9], it remains unclear whether or 68 not this variation is predictable. Specifically, when similar behavioral traits evolve among two or 69 more species, do their neural bases evolve correspondingly? If parallel brain evolution is 70 predictable then it may be possible to understand general principles of neural organization and 71 function across animals. This would expand our ability to manipulate brain function, but if this is 72 not true, new strategies will be needed to reveal the mechanisms of brain evolution. 73Fishes, as both the most speciose (50% of extant vertebrates) and most varied vertebrate 74 radiation [10] offer opportunities to answer these questions. Fish species live in diverse 75 ecological, sensory, and social environments and have evolved elaborate variations in neural 76 structure and function from a common basic ground plan [11] making rapid and variable 77 diversification of brain structures a broad and general feature of their evolution [10]. 78The cichlid fishes of Lake Malawi, Africa offer a particularly striking model of these 79 patterns of diversification. Although geologically young (less than 5 million years old), Lake 80Malawi contains at least 850 species of cichlids [12] that, based on molecular phylogenetic 81 analyses...